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experimental treatment will not be more efficacious than its comparator in the primary endpoint of PFS
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| Name | Class |
|---|---|
| BeiGene | INDUSTRY |
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A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination with Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients with Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
This is a Phase 2 open-label, multicenter study to be conducted concurrently in 3 Parts (Parts A, B, and C). Approximately 232 patients aged 18 years or older with inoperable, histologically confirmed locally advanced or metastatic Gastric or Gastroesophageal Junction (G/GEJ) adenocarcinoma with measurable disease (RECIST v1.1) requiring therapy will be enrolled in the study. Part A and B are designed to evaluate safety, tolerability, and efficacy of the combination therapy of intravenous (IV) DKN-01 and tislelizumab ± CAPOX in G/GEJ adenocarcinoma patients. Treatment continues in repeating 21-day cycles until patient meets criteria for discontinuation or is no longer deriving clinical benefit. Two doses of DKN-01 will be evaluated in Part B (Part B1 and Part B2). Part C is the open-label, randomized, controlled, 2-arm portion of the study to evaluate the efficacy and safety of tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) ± DKN-01 in adult patients with inoperable, histologically confirmed locally advanced or metastatic G/GEJ adenocarcinoma with measurable disease (RECIST v1.1) requiring therapy. Approximately 160 patients will be randomized in a 1:1 ratio to receive either DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6) (n=80) or tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6) (n=80).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A First Line Treatment | Experimental | Part A patients will receive IV DKN-01 (300 mg) on Days 1 and 15, IV tislelizumab (200 mg) on Day 1, IV oxaliplatin (130 mg/m2) on Day 1, and oral capecitabine (1000 mg/m2 twice daily [BID]) on Days 1-15 of each 21-day cycle. Part A is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. |
|
| Part B1 Second Line Treatment | Experimental | Part B patients will receive IV DKN-01 (300 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±Human Epidermal growth factor Receptor 2 [HER2] therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy. |
|
| Part B2 Second Line Treatment | Experimental | Part B patients will receive IV DKN-01 (600 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±HER2 therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DKN-01 300mg | Drug | Administered by IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients | Number of subjects with adverse drug reactions and toxicities as assessed by CTCAE v5.0 CAPOX (capecitabine + oxaliplatin) in patients with inoperable, locally advanced or metastatic G/GEJ adenocarcinoma. | approximately 28 months |
| Part C: Progression Free Survival (PFS) in G/GEJ DKK1 High and Overall Patients Treated With DKN-01 in Combination With Tislelizumab and Chemotherapy vs Tislelizumab and Chemotherapy as a First-line Therapy | PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first. | approximately 30 months |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab + CAPOX as a First-line Therapy | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) through radiological assessment of tumor response, based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Investigators were urged to have the same radiographic imaging modality used throughout the study for each subject (at baseline and at subsequent assessments) in order to provide uniformity of radiographic assessments. |
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Inclusion:
Part A & C:
No previous therapy for cancer. Patients may have received prior neoadjuvant or adjuvant therapy as long it was completed without disease recurrence for at least 6 months since last treatment.
Part B Only:
Disease progression during first-line therapy or within 4 months after the last dose of first-line therapy.
Documentation of elevated Dickkopf-1 (DKK1) messenger ribonucleic acid (mRNA) expression from a fresh tumor biopsy or a biopsy obtained within the 6 months of screening.
Part C Only:
Documentation of programmed cell death protein ligand-1 (PD-L1) combined positive score (CPS) by immunohistochemistry (IHC) and DKK1 mRNA expression in tumor cells by ISH from a fresh tumor biopsy (preferred) or archived tumor biopsy specimen conducted in a Sponsor designated central laboratory.
General:
Able to provide written informed consent prior to any study-specific procedures.
Age ≥18 years on the day of signing the informed consent (exception: ≥19 years in the Republic of Korea).
Confirmed diagnosis of gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma.
One or more tumors measurable on radiographic imaging as defined by Response Evaluation Criteria in Solid Tumor (RECIST) 1.1.
Tumor tissue for mandatory pre-treatment evaluation (fresh biopsy [preferred] or archived specimen).
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 within 7 days of first dose of study drug
Acceptable liver, renal, hematologic, and coagulation function
Females of childbearing potential and male partners of female patients must agree to use adequate contraception during the study and for 6 months after their last dose of study drug.
Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for at least 6 months after the last dose of study drugs.
Exclusion:
Part A & C Only:
Diagnosis of HER2-positive G/GEJ adenocarcinoma.
Unable to swallow capsules or disease significantly affected gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction (for those receiving CAPOX in Part C).
Prior therapy with an anti-programmed cell death protein 1 (PD-1) or anti-PD-L1 antibody.
Part B Only:
Major surgery or chemotherapy within 21 days of first dose of study drug.
General:
Squamous cell or undifferentiated or other histological type of gastric cancer.
Prior therapy with an anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or co-inhibitory checkpoint pathways in any treatment setting (including adjuvant/neoadjuvant) or prior therapy with an anti-DKK1 agent.
Patients with active autoimmune diseases or history of autoimmune diseases that may relapse.
Any condition that required treatment with steroids or any other immune suppressive drugs within 14 days prior to first dose of study drug.
Active leptomeningeal disease or uncontrolled brain metastases.
Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study.
Uncontrolled diabetes or >Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥Grade 3 hypoalbuminemia within 14 days before first dose of study drug.
Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage within 7 days prior to first dose of study drug.
Clinically significant anorexia within 7 days prior to first dose of study drug.
History of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung disease, or uncontrolled systemic diseases.
Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy.
Prior allogeneic stem cell transplantation or organ transplantation.
History of severe hypersensitivity reactions to other monoclonal antibodies or any components of study treatment.
Known dihydropyrimidine dehydrogenase deficiency.
New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.
Known to be human immunodeficiency virus (HIV) positive.
Serious nonmalignant disease
History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that are symptomatic and clinically significant.
Known osteoblastic bony metastasis.
History of gastrointestinal perforation and/or fistulae within 6 months prior to first dose of study drug.
Major surgery 28 days prior to study entry.
Serious psychiatric or medical conditions that could interfere with treatment.
Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for Adverse Events (AEs) not considered a likely safety risk (e.g., alopecia, neuropathy, and specific laboratory abnormalities).
Administration of a live vaccine within 28 days before first dose of study drug.
Active substance abuse.
Pregnant or nursing.
Concurrent participation in another therapeutic clinical study.
Prior radiation therapy within 14 days prior to study entry.
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| Name | Affiliation | Role |
|---|---|---|
| Cynthia Sirard, MD | Chief Medical Officer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic Cancer Center | Phoenix | Arizona | 85054 | United States | ||
| University of Arizona |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42371751 | Derived | Rha SY, Ryu MH, Kim JG, Xu S, Xu Y, Lee KW. Comparative efficacy of tislelizumab + FOLFOX or CAPOX for gastric/gastroesophageal junction adenocarcinoma: an exploratory matching-adjusted indirect comparison. Curr Med Res Opin. 2026 Jun 29:1-11. doi: 10.1080/03007995.2026.2686048. Online ahead of print. | |
| 40341124 | Derived |
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This was a Phase 2 open-label, multicenter study conducted concurrently in 3 parts: Non-randomized Parts A and B, and a randomized Part C.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A First Line Treatment | Part A patients will receive IV DKN-01 (300 mg) on Days 1 and 15, IV tislelizumab (200 mg) on Day 1, IV oxaliplatin (130 mg/m2) on Day 1, and oral capecitabine (1000 mg/m2 twice daily [BID]) on Days 1-15 of each 21-day cycle. Part A is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 300mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 29, 2023 | Jul 28, 2025 |
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| Part C Control First Line Treatment | Active Comparator | Part C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. |
|
| Part C Experimental First Line Treatment | Experimental | Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. |
|
| DKN-01 600mg | Drug | Administered by IV infusion |
|
|
| DKN-01 400mg | Drug | Administered by IV infusion |
|
|
| Tislelizumab 200mg | Drug | Administered by IV infusion |
|
|
| Tislelizumab 400mg | Drug | Administered by IV infusion |
|
|
| Oxaliplatin | Drug | Administered by IV infusion |
|
|
| Capecitabine 1000mg/ m2 twice daily (BID) | Drug | Administered orally |
|
|
| Leucovorin Calcium | Drug | Administered by IV infusion |
|
|
| Fluorouracil | Drug | Administered by IV infusion |
|
|
| approximately 28 months |
| Part B: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | approximately 28 months |
| Part A: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier. | approximately 28 months |
| Part A: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | DoCR is defined as the time from initial complete response (CR) until radiographically documented progressive disease or death due to any cause, whichever is first. | approximately 28 months |
| Part A: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. | approximately 28 months |
| Part A: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. | approximately 28 months |
| Part A: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | DoCB is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks. | approximately 28 months |
| Part A: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | Durable clinical benefit (DCB) is defined as the proportion of patients presenting a Duration of clinical benefit (DoCB) for ≥180 days from initiation of DKN-01. Patients who have a best overall response of PD or those with clinical benefit lasting <180 days are not included. | approximately 28 months |
| Part A: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1. | approximately 28 months |
| Part B: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier. | approximately 28 months |
| Part B: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | Duration of complete response (DoCR) is defined as the time from initial CR until radiographically documented progressive disease or death due to any cause, whichever is first. No patients had a complete response (CR); therefore, the DoCR was not applicable. | approximately 28 months |
| Part B: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. | approximately 28 months |
| Part B: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. | approximately 28 months |
| Part B: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | Duration of clinical benefit (DoCB) is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks. | approximately 28 months |
| Part B: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | DCB rate is defined as the proportion of patients presenting a DoCB (Duration of clinical benefit) for ≥ 180 days from initiation of DKN-01, Patients who have a best overall response of PD or those with clinical benefit lasting <180 days will not be included. | approximately 28 months |
| Part B: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1. | approximately 28 months |
| Part C: To Estimate the Objective Response Rate (ORR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX | approximately 30 months |
| Part C: To Estimate the Duration of Response (DoR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | The duration of response (DoR) is defined only for responders (patients with a BOR of CR or PR) at the time from initial response (CR or PR) until radiographically documented progressive disease or death due to any cause, whichever is earlier. For ORR patient without PD or death, DoR is censored at the most recent tumor assessment before the data cutoff or study withdrawal, whichever occurs first. | approximately 30 months |
| Part C: To Estimate the Overall Survival (OS) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | Overall survival (OS) OS is defined as the time from the date of randomization to death due to any cause. For a patient who is not known to have died by the end of study follow-up, observation of OS is censored at the date the patient was last known to be alive (i.e., date of last contact). Patients lacking data beyond the day of randomization is censored at the date of randomization (i.e., OS duration of 1 day). | approximately 30 months |
| Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first. | approximately 30 months |
| Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Risk difference (RD)(%) or ORR: Positive RD implies the exposure is associated with a higher probability of the outcome occurring. Negative RD indicates the exposure is associated with a lower probability of the outcome occurring. | approximately 30 months |
| Part C: Number of Patients With Toxicity ≥Grade 3 Treatment-related Adverse Events (TRAE) Associated With Each of the Treatment Arms. | To characterize the frequency of toxicity ≥Grade 3 treatment-related adverse events (TRAE) associated with each treatment arm: Control (tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6) and Experimental (DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6)) | approximately 30 months |
| Tucson |
| Arizona |
| 85724 |
| United States |
| City of Hope | Duarte | California | 91010 | United States |
| The Angeles Clinic Research Institute - A Cedars-Sinai Affiliate | Los Angeles | California | 90025 | United States |
| University of Southern California | Los Angeles | California | 90033 | United States |
| UCLA | Los Angeles | California | 90095 | United States |
| Hoag Memorial Hospital Presbyterian | Newport Beach | California | 92663 | United States |
| Chao Family Comprehensive Cancer Center, University of California, Irvine | Orange | California | 92868 | United States |
| University of California San Francisco | San Francisco | California | 94158 | United States |
| Mayo Clinic Florida | Jacksonville | Florida | 32224 | United States |
| AdventHealth Cancer Institute | Orlando | Florida | 32804 | United States |
| Northwestern University Robert H. Lurie Comprehensive Cancer Center | Chicago | Illinois | 60611 | United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| Pontchartrain Cancer Center | Covington | Louisiana | 70433 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Columbia University Irving Medical Center | New York | New York | 10032 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Wisconsin Carbone Cancer Center | Madison | Wisconsin | 53792 | United States |
| Charité Universitätsmedizin Berlin | Berlin | 13353 | Germany |
| Institut Fur Klinisch Onkologische Forschung Am Krankenhaus Nordwest | Frankfurt | 60488 | Germany |
| Hämatologisch-Onkologische Praxis Eppendorf (HOPE) | Hamburg | 20249 | Germany |
| Universitatsklinikum Heidelberg | Heidelberg | 69120 | Germany |
| Slk-Kliniken | Heilbronn | 74078 | Germany |
| Studienzentrum Onkologie Ravensburg | Ravensburg | 88212 | Germany |
| Caritas Klinikum Saarbrücken St. Theresia | Saarbrücken | 66113 | Germany |
| CHA Bundang Medical Center | Seongnam-si | Gyeonggi-do | 13520 | South Korea |
| Korea University Ansan Hospital | Ansan-si | 15355 | South Korea |
| Hallym University Sacred Heart Hospital | Anyang | 14068 | South Korea |
| Dong-A University Hospital | Busan | 49201 | South Korea |
| National Cancer Center | Goyang | 10408 | South Korea |
| Gachon University Gil Medical Center | Incheon | 21565 | South Korea |
| Inha University Hospital | Incheon | 22332 | South Korea |
| Seoul National University Bundang Hospital | Seongnam | 13620 | South Korea |
| Korea University Anam Hospital | Seoul | 02841 | South Korea |
| Hanyang University Hospital | Seoul | 04763 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Boramae Hospital SNU | Seoul | 07061 | South Korea |
| Korea University Guro Hospital | Seoul | 08308 | South Korea |
| Seoul National University Hospital | Seoul | 3080 | South Korea |
| Severance Hospital, Yonsei University Health System | Seoul | 3722 | South Korea |
| Samsung Medical Center | Seoul | 6351 | South Korea |
| The Catholic University of Korea St. Mary's Hospital | Seoul | 6591 | South Korea |
| The Catholic University of Korea St. Vincent's Hospital | Suwon | 16247 | South Korea |
| Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036. |
| 39432867 | Derived | Klempner SJ, Sonbol MB, Wainberg ZA, Uronis HE, Chiu VK, Scott AJ, Iqbal S, Tejani MA, Chung V, Stilian MC, Thoma M, Zhang Y, Kagey MH, Baum J, Sirard CA, Altura RA, Ajani JA. DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish. J Clin Oncol. 2025 Jan 20;43(3):339-349. doi: 10.1200/JCO.24.00410. Epub 2024 Oct 21. |
| FG001 | Part B1 Second Line Treatment | Part B patients will receive IV DKN-01 (300 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have Dickkopf-1 (DKK1)-high (H-score ≥ 35) gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±human epidermal growth factor receptor 2 (HER2) therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy. DKN-01 300mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion |
| FG002 | Part B2 Second Line Treatment | Part B patients will receive IV DKN-01 (600 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±HER2 therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion |
| FG003 | Part C Control First Line Treatment | Part C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion |
| FG004 | Part C Experimental First Line Treatment | Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion |
| COMPLETED |
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| NOT COMPLETED |
|
|
Parts A & B planned for 72 subjects enrolled: 25 subjects enrolled in Part A, 53 subjects enrolled in Part B. The Safety population consisted of 25 subjects in Part A, 52 subjects in Part B; the modified Intent-to-Treat population consisted of 22 subjects in Part A, 52 patients in Part B. Part C planned for 160 subjects enrolled: 170 subjects were randomized, with 84 treated subjects in the experimental group, 85 treated subjects in the control group.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A First Line Treatment | Part A patients will receive IV DKN-01 (300 mg) on Days 1 and 15, IV tislelizumab (200 mg) on Day 1, IV oxaliplatin (130 mg/m2) on Day 1, and oral capecitabine (1000 mg/m2 twice daily [BID]) on Days 1-15 of each 21-day cycle. Part A is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 300mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion |
| BG001 | Part B1 Second Line Treatment | Part B patients will receive IV DKN-01 (300 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±HER2 therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy. DKN-01 300mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion |
| BG002 | Part B2 Second Line Treatment | Part B patients will receive IV DKN-01 (600 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±HER2 therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion |
| BG003 | Part C Control First Line Treatment | Part C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion |
| BG004 | Part C Experimental First Line Treatment | Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| |||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||
| Region of Enrollment | 25 patients from the USA were enrolled in Part A, and 53 patients from the USA and The Republic of South Korea were enrolled in Part B. The Safety population consisted of 25 patients in Part A and 52 patients in Part B, and the modified Intent-to-Treat (mITT) population consisted of 22 patients in Part A and 52 patients in Part B. In Part C, 170 patients were randomized from the USA, The Republic of South Korea, and Germany. The Safety population consisted of 169 patients and the Intent-to-Treat (ITT) population consisted of 170 patients. | Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea. | Count of Participants | Participants |
| |||||||||
| Body Surface Area (BSA) | Some subject data in Part C not available for analysis of BSA | Mean | Standard Deviation | m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients | Number of subjects with adverse drug reactions and toxicities as assessed by CTCAE v5.0 CAPOX (capecitabine + oxaliplatin) in patients with inoperable, locally advanced or metastatic G/GEJ adenocarcinoma. | In Parts A and B, 25 patients were enrolled in Part A and 53 patients were enrolled in Part B. The Safety population consisted of 25 patients in Part A and 52 patients in Part B, and the modified Intent-to-Treat (mITT) population consisted of 22 patients in Part A and 52 patients in Part B. | Posted | Count of Participants | Participants | approximately 28 months |
|
|
| ||||||||||||||||||||||||||||||||
| Primary | Part C: Progression Free Survival (PFS) in G/GEJ DKK1 High and Overall Patients Treated With DKN-01 in Combination With Tislelizumab and Chemotherapy vs Tislelizumab and Chemotherapy as a First-line Therapy | PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first. | Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX; Control group: Tislelizumab + CAPOX/FOLFOX | Posted | Median | 95% Confidence Interval | Months | approximately 30 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part A: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab + CAPOX as a First-line Therapy | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) through radiological assessment of tumor response, based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Investigators were urged to have the same radiographic imaging modality used throughout the study for each subject (at baseline and at subsequent assessments) in order to provide uniformity of radiographic assessments. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. | Posted | Number | 95% Confidence Interval | percentage of patients | approximately 28 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part B: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. | Posted | Number | 95% Confidence Interval | percentage of patients | approximately 28 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part A: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. Patients who do not experience PD or death at the time of the analysis were censored. | Posted | Median | 95% Confidence Interval | months | approximately 28 months |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Part A: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | DoCR is defined as the time from initial complete response (CR) until radiographically documented progressive disease or death due to any cause, whichever is first. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. | Posted | Median | 95% Confidence Interval | months | approximately 28 months |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Part A: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. | Posted | Median | 95% Confidence Interval | Months | approximately 28 months |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Part A: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. | The mITT population is defined as all patients who received more than one dose of DKN-01. | Posted | Median | 95% Confidence Interval | months | approximately 28 months |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Part A: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | DoCB is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. Patients who do not experience PD or death at the time of the analysis were censored. | Posted | Median | 95% Confidence Interval | months | approximately 28 months |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Part A: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | Durable clinical benefit (DCB) is defined as the proportion of patients presenting a Duration of clinical benefit (DoCB) for ≥180 days from initiation of DKN-01. Patients who have a best overall response of PD or those with clinical benefit lasting <180 days are not included. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. | Posted | Number | 95% Confidence Interval | percentage of patients | approximately 28 months |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Part A: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. | Posted | Number | 95% Confidence Interval | percentage of patients | approximately 28 months |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Part B: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. Patients who do not experience progressive disease (PD) or death at the time of the analysis were censored. The median DoR was not reached in the 300 mg dose group. | Posted | Median | 95% Confidence Interval | months | approximately 28 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part B: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | Duration of complete response (DoCR) is defined as the time from initial CR until radiographically documented progressive disease or death due to any cause, whichever is first. No patients had a complete response (CR); therefore, the DoCR was not applicable. | Not Posted | approximately 28 months | Participants | |||||||||||||||||||||||||||||||||||||
| Secondary | Part B: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. | The mITT population is defined as all patients who received more than one dose of DKN-01. | Posted | Median | 95% Confidence Interval | months | approximately 28 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part B: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. | The mITT population is defined as all patients who received more than one dose of DKN-01. | Posted | Median | 95% Confidence Interval | months | approximately 28 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part B: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | Duration of clinical benefit (DoCB) is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. Patients who do not experience PD or death at the time of the analysis were censored. | Posted | Median | 95% Confidence Interval | months | approximately 28 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part B: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | DCB rate is defined as the proportion of patients presenting a DoCB (Duration of clinical benefit) for ≥ 180 days from initiation of DKN-01, Patients who have a best overall response of PD or those with clinical benefit lasting <180 days will not be included. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. | Posted | Number | 95% Confidence Interval | percentage of patients | approximately 28 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part B: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1. | The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. | Posted | Number | 95% Confidence Interval | percentage of patients | approximately 28 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part C: To Estimate the Objective Response Rate (ORR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX | Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX | Posted | Number | 95% Confidence Interval | percentage of patients | approximately 30 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part C: To Estimate the Duration of Response (DoR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | The duration of response (DoR) is defined only for responders (patients with a BOR of CR or PR) at the time from initial response (CR or PR) until radiographically documented progressive disease or death due to any cause, whichever is earlier. For ORR patient without PD or death, DoR is censored at the most recent tumor assessment before the data cutoff or study withdrawal, whichever occurs first. | Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX | Posted | Median | 95% Confidence Interval | months | approximately 30 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part C: To Estimate the Overall Survival (OS) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | Overall survival (OS) OS is defined as the time from the date of randomization to death due to any cause. For a patient who is not known to have died by the end of study follow-up, observation of OS is censored at the date the patient was last known to be alive (i.e., date of last contact). Patients lacking data beyond the day of randomization is censored at the date of randomization (i.e., OS duration of 1 day). | Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX | Posted | Median | 95% Confidence Interval | months | approximately 30 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first. | Intent-to-Treat (ITT): All patients randomized to treatment. Patients will be included in the treatment group assigned at randomization regardless of the actual treatment received. Experimental: DKK1+tislelizumab+(CAPOX/mFOLFOX6), Control: tislelizumab+(CAPOX/mFOLFOX6). | Posted | Median | 95% Confidence Interval | Months | approximately 30 months |
| |||||||||||||||||||||||||||||||||
| Secondary | Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Risk difference (RD)(%) or ORR: Positive RD implies the exposure is associated with a higher probability of the outcome occurring. Negative RD indicates the exposure is associated with a lower probability of the outcome occurring. | Intent-to-Treat (ITT): All patients randomized to treatment. Patients will be included in the treatment group assigned at randomization regardless of the actual treatment received. Experimental: DKK1+tislelizumab+(CAPOX/mFOLFOX6), Control: tislelizumab+(CAPOX/mFOLFOX6). | Posted | Number | 95% Confidence Interval | percentage | approximately 30 months |
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| Secondary | Part C: Number of Patients With Toxicity ≥Grade 3 Treatment-related Adverse Events (TRAE) Associated With Each of the Treatment Arms. | To characterize the frequency of toxicity ≥Grade 3 treatment-related adverse events (TRAE) associated with each treatment arm: Control (tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6) and Experimental (DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6)) | 170 patients were randomized and 169 patients were treated with study medication: 84 in the Experimental group and 85 in the Control group. | Posted | Number | number of patients | approximately 30 months |
|
Up to 30 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A First Line Treatment | Part A patients will receive IV DKN-01 (300 mg) on Days 1 and 15, IV tislelizumab (200 mg) on Day 1, IV oxaliplatin (130 mg/m2) on Day 1, and oral capecitabine (1000 mg/m2 twice daily [BID]) on Days 1-15 of each 21-day cycle. Part A is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 300mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion | 18 | 25 | 11 | 25 | 25 | 25 |
| EG001 | Part B1 Second Line Treatment | Part B patients will receive IV DKN-01 (300 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±HER2 therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy. DKN-01 300mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion | 14 | 24 | 13 | 24 | 23 | 24 |
| EG002 | Part B2 Second Line Treatment | Part B patients will receive IV DKN-01 (600 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±HER2 therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion | 16 | 28 | 13 | 28 | 24 | 28 |
| EG003 | Part C Control First Line Treatment | Part C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion | 48 | 85 | 33 | 85 | 82 | 85 |
| EG004 | Part C Experimental First Line Treatment | Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion | 38 | 85 | 37 | 85 | 83 | 85 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cardiogenic shock | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Eosinophilic myocarditis | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Ophthalmoplegia | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal incarcerated hernia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Entercolitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gastric perforation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Immune-mediated enterocolitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Intestinal ischaemia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Obstruction gastric | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Subileus | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Biliary obstruction | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Norovirus infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood calcium decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Hemoglobin decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Liver function test increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Type 1 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Immune-mediated hepatitis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Biliary tract infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Spontaneous bacterial peritonitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Retching | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Eructation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Anal haemorrhage | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oesophageal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oral dysaesthesia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Malignant gastrointestinal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Obstruction gastric | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cheilitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Irritable bowel syndrome | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Duodenal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Enterocolitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Lip pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Mucous stools | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oesophageal food impaction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Tongue discolouration | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oral discharge | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Troponin T increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Electrocardiogram ST segment abnormal | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Human chorionic gonadotropin increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Blood creatine increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Troponin I increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Urine output decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Food aversion | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Type 1 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypophagia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Taste disorder | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vocal cord paresis | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Temperature intolerance | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Medical device pain | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Discomfort | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Infusion site pain | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Medical device site erosion | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Early satiety | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cyst | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Feeling cold | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hernia | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Infusion site extravasation | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Infusion site rash | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Onychomadesis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Lichenoid keratosis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Nail bed inflammation | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Penile ulceration | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Skin erosion | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Skin hypopigmentation | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Skin odour abnormal | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dyspnoea paroxysmal nocturnal | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Laryngospasm | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Throat tightness | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Sacral pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Trismus | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Spondylolisthesis | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Onychomycosis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Viraemia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Body tinea | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Gingivitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Parotitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Penile infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Respiratory syncytial virus infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Vaginal infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Pneumonia aspiration | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Iron deficiency | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Foreign body in eye | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Tendon injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Vascular access site pain | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Eyelid injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Vascular access complication | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Skin injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dermatochalasis | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Photopsia | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Retinal haemorrhage | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Retinopathy | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Retinal exudates | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Corneal erosion | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Detachment of retinal pigment epithelium | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diabetic retinopathy | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dry age-related macular degeneration | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Eye pruritus | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyalosis asteroid | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Keratitis | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Macular degeneration | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Ocular hyperaemia | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pterygium | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Retinal degeneration | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Retinal drusen | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Subretinal fluid | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Uveitis | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Xerophthalmia | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Superficial vein thrombosis | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Aortic thrombosis | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Adjustment disorder with anxiety | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Restlessness | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Calculus urinary | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Glycosuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Micturition urgency | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Renal pain | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urinary tract pain | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urine odour abnormal | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Arteriosclerosis coronary artery | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Left ventricular failure | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Sinus arrhythmia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Tricuspid valve incompetence | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Sinus node dysfunction | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Deafness | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoacusis | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pruritus genital | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.1 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.1 | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.1 | Systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.1 | Systematic Assessment |
|
The study was terminated prematurely due to lack of efficacy. Therefore, only limited efficacy analyses were performed on the primary and limited secondary efficacy endpoints. Parts A+B were initiated and completed. Part C was initiated upon completion of Parts A+B. Due to termination of the program during Part C, combined analysis for Parts A+B and C was not performed.
At least 45 days prior to submission for Publication, Institution submits proposed Publication to Sponsor. Review Period for abstracts/poster presentations is 30 days. Sponsor may notify Institution in writing that patent applications will be filed and publication may be deferred up to 60 days. If Publication has Sponsor Confidential Information (CI) & Sponsor requests Institution to delete CI, Institution agrees to delete CI if it does not preclude the accurate interpretation of Study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Douglas Onsi / President and CEO | Leap Therapeutics, Inc. | 617-218-1116 | donsi@leaptx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: SAP Part A+B | Oct 3, 2022 | Jul 28, 2025 | SAP_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: SAP Part C | Feb 6, 2025 | Jul 28, 2025 | SAP_002.pdf |
Not provided
| ID | Term |
|---|---|
| D013274 | Stomach Neoplasms |
| D009369 | Neoplasms |
| D000230 | Adenocarcinoma |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
| ID | Term |
|---|---|
| C000707970 | tislelizumab |
| D000077150 | Oxaliplatin |
| D000069287 | Capecitabine |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
Not provided
Not provided
|
|
|
|
|
|
| United States |
|
|
| Germany |
|
|
|
| OG001 | Part C Experimental First Line Treatment | Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
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|
|
|
|
|
|
|
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|
|
|
|
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|
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|
Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
DKN-01 600mg: Administered by IV infusion
DKN-01 400mg: Administered by IV infusion
Tislelizumab 200mg: Administered by IV infusion
Tislelizumab 400mg: Administered by IV infusion
Oxaliplatin: Administered by IV infusion
Capecitabine 1000mg/ m2 BID: Administered orally
Leucovorin Calcium: Administered by IV infusion
Fluorouracil: Administered by IV infusion
|
|
|
Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion |
|
|
Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months. DKN-01 600mg: Administered by IV infusion DKN-01 400mg: Administered by IV infusion Tislelizumab 200mg: Administered by IV infusion Tislelizumab 400mg: Administered by IV infusion Oxaliplatin: Administered by IV infusion Capecitabine 1000mg/ m2 BID: Administered orally Leucovorin Calcium: Administered by IV infusion Fluorouracil: Administered by IV infusion |
|
|
| OG001 | PFS DKK1-high Patients, Part C Control | Part C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
|
| OG002 | PFS All Patients, Part C Experimental | Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
|
| OG003 | PFS All Patients, Part C Control | Part C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
|
|
|
|
| OG001 | ORR DKK1-high Patient, Part C Control | Part C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
|
| OG002 | ORR All Patients, Part C Experimental | Part C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
|
| OG003 | ORR All Patients, Part C Control | Part C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
|
|
|
|
|
|