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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2020-08370 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 10403 | Other Identifier | Dana-Farber - Harvard Cancer Center LAO | |
| 10403 | Other Identifier | CTEP | |
| UM1CA186709 | U.S. NIH Grant/Contract | View source |
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This phase I trial identifies the best dose, possible benefits and/or side effects of gemcitabine in combination with elimusertib (BAY 1895344) in treating patients with pancreatic, ovarian, and other solid tumors that have spread to other places in the body (advanced). Gemcitabine is a chemotherapy drug that blocks the cell from making DNA and may kill tumor cells. elimusertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and elimusertib in combination may shrink or stabilize cancer.
PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of gemcitabine in combination with elimusertib (BAY 1895344), as assessed by Common Terminology Criteria for Adverse Events (CTCAE) 5.0. (Dose Escalation and Expansion Cohort) II. Determine the maximum tolerated dose (MTD) of gemcitabine in combination with elimusertib (BAY 1895344). (Dose Escalation Cohort)
SECONDARY OBJECTIVES:
I. To observe and record anti-tumor activity. II. Analyze the pharmacokinetic (PK) profile of the gemcitabine and elimusertib (BAY 1895344) combination.
III. Assessing whether immunohistochemical markers of deoxyribonucleic acid (DNA) damage, gamma-H2AX and phosphorylated (p)NBS1, increase in on-treatment biopsies compared to the levels seen in pre-treatment biopsies.
EXPLORATORY OBJECTIVES:
I. Explore biomarkers that predict response to this combination. II. Evaluate mechanisms of acquired resistance to this combination.
OUTLINE: This is a dose-escalation study of gemcitabine followed by a dose expansion study.
Patients receive gemcitabine intravenously (IV) over 30 minutes on days 1 and 8 and elimusertib orally (PO) once daily (QD) or twice daily (BID) on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial and collection of blood samples during screening and on days 1, 2, and 9-10 of cycle 1. Patients in the dose-expansion portion of the trial also undergo biopsies during screening and on day 9 of cycle 1.
After completion of study treatment, patients are followed up for 30 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (gemcitabine, elimusertib) | Experimental | Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and elimusertib QD or PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial and collection of blood samples during screening and on days 1, 2, and 9-10 of cycle 1. Patients in the dose-expansion portion of the trial also undergo biopsies during screening and on day 9 of cycle 1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biopsy Procedure | Procedure | Undergo biopsy (dose expansion cohort only) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients on Treatment With Related Adverse Events | The toxicity of the combination of gemcitabine plus elimusertib will be assessed with Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 criteria. The safety and tolerability were evaluated using the number of treatment-related adverse events. | Adverse events were recorded between the first patient treated (June 2021) and 30 days out from the last patient ending treatment (October 2024) (3 years and 4 months). Adverse events were collected for a median of 88.5 days, ranging 58 - 315 days. |
| Maximum Tolerated Dose (MTD) | A conventional algorithm (3+3 design) will be used to identify the MTD, escalating on zero of three or one of six dose-limiting toxicities (DLTs), and de-escalating if two DLTs are encountered. The MTD will be the highest dose level at which zero of three or one of six subjects experience a DLT. The MTD was not reached due to toxicity experienced during cycle 1. | The MTD was evaluated during the dose-escalation phase, occurring from the first patient on treatment (Jun '21) through the last patient's last dose (Sep '24) (3 years and 3 months). MTD was evaluated for a median of 58.5 days, ranging 28 - 285 days. |
| Overall Response Rate (ORR) | Radiological response will be assessed with Response Evaluation Criteria in Solid Tumors 1.1 criteria and will be portrayed as the percentage of subjects with a complete response (CR) and partial response (PR). | ORR was assessed from the time of the first patient on study (June 2021) through the last patient off study (October 2024). ORR was calculated for a median of 103 days, ranging from 30 - 312 days. |
| Duration of Response | Duration of response was assessed from the time of the first patient on treatment (June 2021) through the last patient off study (October 2024). Duration of response was calculated for a median of 103 days, ranging from 30 - 312 days. | |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine | Individual PK parameters will be estimated for the maximum concentration (Cmax), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively. |
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Inclusion Criteria:
DOSE ESCALATION COHORT:
Patients must have histologically confirmed solid tumor malignancy that is not curable with standard approaches. Gemcitabine must be considered a standard therapy for the participant's malignancy
Patients must have a measurable disease, in at least one lesion, for both the dose escalation and expansion cohorts, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
Patients must have received one line of treatment for their incurable cancer before enrolling in this trial. Patients with rare malignancies for which there is no accepted standard chemotherapy regimen can enroll without any prior treatments
Patients must not have received more than two lines of cytotoxic chemotherapy
DOSE EXPANSION COHORT:
Participants must have a histologically confirmed advanced pancreatic adenocarcinoma or ovarian cancer (high grade serous ovarian, primary peritoneal or fallopian tube cancer) that is not curable with standard approaches. Patients with both metastatic pancreatic cancer and unresectable pancreatic cancer are eligible
Ovarian cancer:
Pancreatic cancer:
Patients with pancreatic cancer cannot have received more than one line of cytotoxic chemotherapy in the metastatic setting
Patients must have a biopsiable disease and at least one separate measurable lesion
DOSE ESCALATION AND EXPANSION COHORTS:
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Age >= 18 years
Leukocytes >= 3,000/mcL
Hemoglobin >= 10 g/dL (no red blood cell transfusion is allowed within 3 weeks before starting the trial)
Neutrophil count >= 1,500 K/mcL (participants must not have received colony stimulating factors [e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor or recombinant erythropoietin] within 3 weeks before initiation of protocol therapy)
Platelets >= 100,000 /mcL
Albumin >= 2.8 mg/dL
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN
Creatinine clearance =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with treated brain metastases or primary brain tumors are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for >= 4 weeks after the last date of treatment are permitted, and if they are no longer taking corticosteroids for at least 4 weeks prior to beginning the protocol
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial with permission of the principal investigator of the trial
Patients with known history or current clinically significant symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
The effects of elimusertib (BAY 1895344) on the developing human fetus are unknown. For this reason and because DNA-damage response inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 6 months after completion of elimusertib (BAY 1895344) administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of elimusertib (BAY 1895344) administration
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James M Cleary | Dana-Farber - Harvard Cancer Center LAO | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cancer Institute Developmental Therapeutics Clinic | Bethesda | Maryland | 20892 | United States | ||
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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The study did not progress into the dose expansion cohort and therefore no participants were enrolled into this arm.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Escalation Level 1: 250 MG/M2 GEMCITABINE D1, 8 + 40 MG BAY1895344 (ELIMUSERTIB) BID D1-3,8-10 | Patients in Dose Escalation Level 1 received 250 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 40mg elimusertib PO BID on days 1-3 and 8-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| 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_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 26, 2024 |
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| Biospecimen Collection | Procedure | Undergo collection of blood samples |
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| Diagnostic Imaging Testing | Procedure | Undergo medical imaging scans |
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| Elimusertib | Drug | Given PO |
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| Gemcitabine | Drug | Given IV |
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| Progression Free Survival (PFS) |
| PFS was evaluated from the first patient on study (Jun '21) through the last patient's death or date of progressive disease (Sep '24) (3 years and 3 months). PFS was calculated for a median of 90 days, ranging 25 - 286 days. |
| Overall Survival | Overall survival (OS) was evaluated from the first patient on study (June 2021) through the last patient's death or off study date (October 2024). | OS was calculated for a median of 103 days, ranging from 30 - 312 days. |
| Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant. |
| Gemcitabine Pharmacokinetics | The CDA phenotype will be correlated with gemcitabine half-life, AUC and the dFdU/gemcitabine metabolic ratio. | Days 1 and 8 of cycle 1 dose-escalation (first patient's day 1, June 2021, to last patient's day 8, December 2023) equaling the total collection time of 2 year and 6 months. Samples were collected on two days for each participant. |
| Presence or Absence of Homologous Recombination (HR) Repair Proficiency (Dose Expansion) | Will be defined according to formation of RAD51 foci. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time. | Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort |
| Presence or Absence of ATR Activation (Dose Expansion) | Will be defined by the expression of pATR and pCHK1. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time. | Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort |
| Increase in Deoxyribonucleic Acid (DNA) Damage Level (Dose Expansion) | Changes in immunohistochemical markers of DNA damage, gamma-H2AX and phosphorylated (p)NBS1. | Pre-treatment and on-treatment in the dose expansion cohort |
| Conversion of Cancer With Stable Replication Forks to One With Unstable Replication Forks (Dose Expansion) | DNA fiber assays will be used to assess whether gemcitabine/elimusertib treatment converts a cancer with stable replication forks to one with unstable replication forks. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time. | Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort |
| Presence or Absence of Replication Stress (Dose Expansion) | Will be defined at the gene expression and protein levels for phosphorylated (p)KAP1, pRPA32, cyclin E and MYC. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time. | Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort. |
| Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine | Individual PK parameters will be estimated for the area under the concentration-time curve (AUC), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively. | Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant. |
| Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine | Individual PK parameters will be estimated for the half-life (t1/2), apparent clearance (Cl/F) and apparent volume of distribution (V/F), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively. | Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant. |
| National Institutes of Health Clinical Center |
| Bethesda |
| Maryland |
| 20892 |
| United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| FG001 | Dose Escalation Level B1: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level B1 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| FG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| FG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| FG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| FG005 | Dose Expansion Cohort | Participants were not enrolled into the dose expansion cohort due to the study not progressing into the next phase. The recommended phase 2 dose was not found. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Escalation Level 1: 250 MG/M2 GEMCITABINE D1, 8 + 40 MG BAY1895344 (ELIMUSERTIB) BID D1-3,8-10 | Patients in Dose Escalation Level 1 received 250 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 40mg elimusertib PO BID on days 1-3 and 8-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| BG001 | Dose Escalation Level B1: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level B1 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| BG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| BG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| BG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| 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 | ||||||||||||||||||||||||||||||||
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| Primary | Number of Patients on Treatment With Related Adverse Events | The toxicity of the combination of gemcitabine plus elimusertib will be assessed with Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 criteria. The safety and tolerability were evaluated using the number of treatment-related adverse events. | Posted | Count of Participants | Participants | Adverse events were recorded between the first patient treated (June 2021) and 30 days out from the last patient ending treatment (October 2024) (3 years and 4 months). Adverse events were collected for a median of 88.5 days, ranging 58 - 315 days. |
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| Primary | Maximum Tolerated Dose (MTD) | A conventional algorithm (3+3 design) will be used to identify the MTD, escalating on zero of three or one of six dose-limiting toxicities (DLTs), and de-escalating if two DLTs are encountered. The MTD will be the highest dose level at which zero of three or one of six subjects experience a DLT. The MTD was not reached due to toxicity experienced during cycle 1. | Posted | Number | mg | The MTD was evaluated during the dose-escalation phase, occurring from the first patient on treatment (Jun '21) through the last patient's last dose (Sep '24) (3 years and 3 months). MTD was evaluated for a median of 58.5 days, ranging 28 - 285 days. |
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| Primary | Overall Response Rate (ORR) | Radiological response will be assessed with Response Evaluation Criteria in Solid Tumors 1.1 criteria and will be portrayed as the percentage of subjects with a complete response (CR) and partial response (PR). | Posted | Number | percent of participants | ORR was assessed from the time of the first patient on study (June 2021) through the last patient off study (October 2024). ORR was calculated for a median of 103 days, ranging from 30 - 312 days. |
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| Primary | Duration of Response | Only one participant showed a response to study treatment. This participant was in Dose Level 1. All participants were assessed for duration of response. | Posted | Mean | Full Range | months | Duration of response was assessed from the time of the first patient on treatment (June 2021) through the last patient off study (October 2024). Duration of response was calculated for a median of 103 days, ranging from 30 - 312 days. |
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| Primary | Progression Free Survival (PFS) | PFS could not be calculated for each individual cohort due to insufficient number of participants with events. Therefore, PFS has been reported for the entire study population. | Posted | Median | 95% Confidence Interval | months | PFS was evaluated from the first patient on study (Jun '21) through the last patient's death or date of progressive disease (Sep '24) (3 years and 3 months). PFS was calculated for a median of 90 days, ranging 25 - 286 days. |
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| Primary | Overall Survival | Overall survival (OS) was evaluated from the first patient on study (June 2021) through the last patient's death or off study date (October 2024). | Posted | Mean | Full Range | days | OS was calculated for a median of 103 days, ranging from 30 - 312 days. |
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| Secondary | Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine | Individual PK parameters will be estimated for the maximum concentration (Cmax), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively. | No samples were collected in Dose Escalation Level B4 and Dose Escalation Level 1ESC cohorts. Therefore, no data has been entered for these cohorts. | Posted | Mean | Standard Deviation | µg/L | Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant. |
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| Secondary | Gemcitabine Pharmacokinetics | The CDA phenotype will be correlated with gemcitabine half-life, AUC and the dFdU/gemcitabine metabolic ratio. | The trial ended early due to toxicity. No gem PK analyses were run, as none of the samples were analyzed for this assessment prior to study termination and all samples have been destroyed. | Posted | Days 1 and 8 of cycle 1 dose-escalation (first patient's day 1, June 2021, to last patient's day 8, December 2023) equaling the total collection time of 2 year and 6 months. Samples were collected on two days for each participant. |
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| Secondary | Presence or Absence of Homologous Recombination (HR) Repair Proficiency (Dose Expansion) | Will be defined according to formation of RAD51 foci. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time. | The trial ended early due to toxicity. The Dose Expansion Cohort was not initiated and no participants could be assessed for this Outcome Measure. | Posted | Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort |
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| Secondary | Presence or Absence of ATR Activation (Dose Expansion) | Will be defined by the expression of pATR and pCHK1. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time. | The trial ended early due to toxicity. The Dose Expansion Cohort was not initiated and no participants could be assessed for this Outcome Measure. | Posted | Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort |
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| Secondary | Increase in Deoxyribonucleic Acid (DNA) Damage Level (Dose Expansion) | Changes in immunohistochemical markers of DNA damage, gamma-H2AX and phosphorylated (p)NBS1. | The trial ended early due to toxicity. The Dose Expansion Cohort was not initiated and no participants could be assessed for this Outcome Measure. | Posted | Pre-treatment and on-treatment in the dose expansion cohort |
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| Secondary | Conversion of Cancer With Stable Replication Forks to One With Unstable Replication Forks (Dose Expansion) | DNA fiber assays will be used to assess whether gemcitabine/elimusertib treatment converts a cancer with stable replication forks to one with unstable replication forks. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time. | The trial ended early due to toxicity. The Dose Expansion Cohort was not initiated and no participants could be assessed for this Outcome Measure. | Posted | Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort |
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| Secondary | Presence or Absence of Replication Stress (Dose Expansion) | Will be defined at the gene expression and protein levels for phosphorylated (p)KAP1, pRPA32, cyclin E and MYC. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time. | The trial ended early due to toxicity. The Dose Expansion Cohort was not initiated and no participants could be assessed for this Outcome Measure. | Posted | Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort. |
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| Secondary | Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine | Individual PK parameters will be estimated for the area under the concentration-time curve (AUC), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively. | No samples were collected in Dose Escalation Level B4 and Dose Escalation Level 1ESC cohorts. Therefore, no data has been entered for these cohorts. | Posted | Mean | Standard Deviation | mg/L•h | Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant. |
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| Secondary | Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine | Individual PK parameters will be estimated for the half-life (t1/2), apparent clearance (Cl/F) and apparent volume of distribution (V/F), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively. | The trial ended early due to toxicity. Samples were not analyzed for these assessments prior to early study termination at which point all samples destroyed and no data collected. | Posted | Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant. |
|
Adverse events were reviewed and reported after the initial dose of study treatment, during treatment, and within 30 days of the last dose of treatment. Adverse events were recorded between the first patient treated (June 2021) and 30 days out from the last patient ending treatment (October 2024), equaling a collection time of 3 years and 4 months. Adverse events were collected for a median of 88.5 days, ranging 58 - 315 days.
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 | Dose Escalation Level 1: 250 MG/M2 GEMCITABINE D1, 8 + 40 MG BAY1895344 (ELIMUSERTIB) BID D1-3,8-10 | Patients in Dose Escalation Level 1 received 250 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 40mg elimusertib PO BID on days 1-3 and 8-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. | 1 | 3 | 3 | 3 | 3 | 3 |
| EG001 | Dose Escalation Level B1: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level B1 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. | 0 | 2 | 2 | 2 | 2 | 2 |
| EG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. | 1 | 3 | 1 | 3 | 3 | 3 |
| EG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. | 1 | 3 | 2 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Dysuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Gallbladder obstruction | Hepatobiliary disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Peritoneal infection | Investigations | Systematic Assessment |
| ||
| Platelet count decreased | Investigations | Systematic Assessment |
| ||
| Small intestinal obstruction | Gastrointestinal disorders | Systematic Assessment |
| ||
| Thromboembolic event | Vascular disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| White blood cell decreased | Investigations | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
| ||
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
| ||
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Bloating | Gastrointestinal disorders | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Blood lactate dehydrogenase increased | Investigations | Systematic Assessment |
| ||
| Blurred vision | Eye disorders | Systematic Assessment |
| ||
| body aches | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Bone pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Cellulitis-left ankle | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Creatinine increased | Investigations | Systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Dental caries | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Dry eye | Eye disorders | Systematic Assessment |
| ||
| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Dysgeusia | Nervous system disorders | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Edema limbs | General disorders | Systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
| ||
| Flu like symptoms | General disorders | Systematic Assessment |
| ||
| Flushing | Vascular disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Hot flashes | Vascular disorders | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperhidrosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperphosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Insomnia | Psychiatric disorders | Systematic Assessment |
| ||
| Lymphocyte count decreased | Investigations | Systematic Assessment |
| ||
| Mucositis oral | Investigations | Systematic Assessment |
| ||
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Non-cardiac chest pain | General disorders | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Pelvic pain | Reproductive system and breast disorders | Systematic Assessment |
| ||
| Platelet count decreased | Investigations | Systematic Assessment |
| ||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| premature atrial contraction/bigeminy) | Cardiac disorders | Systematic Assessment |
| ||
| Proteinuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Rash acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sinus bradycardia | Cardiac disorders | Systematic Assessment |
| ||
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Skin hypopigmentation | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Soft tissue infection | Infections and infestations | Systematic Assessment |
| ||
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Toothache | Gastrointestinal disorders | Systematic Assessment |
| ||
| Urinary frequency | Renal and urinary disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Weight loss | Investigations | Systematic Assessment |
| ||
| White blood cell decreased | Investigations | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| James Cleary, MD | Dana Farber Cancer Institute | 6176326073 | james_cleary@dfci.harvard.edu |
| Mar 27, 2026 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 26, 2024 | Mar 27, 2026 | ICF_001.pdf |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| D005185 | Fallopian Tube Neoplasms |
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D005184 | Fallopian Tube Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D010049 | Ovarian Diseases |
| D006058 | Gonadal Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D001706 | Biopsy |
| D013048 | Specimen Handling |
| D014965 | X-Rays |
| C000711582 | BAY 1895344 |
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D060733 | Electromagnetic Radiation |
| D055590 | Electromagnetic Phenomena |
| D060328 | Magnetic Phenomena |
| D055585 | Physical Phenomena |
| D011827 | Radiation |
| D011839 | Radiation, Ionizing |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
|
|
| OG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
|
|
| OG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
|
|
| OG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG005 | Total Study Population | Participants have been grouped from all cohorts into this one cumulative cohort, as PFS could not be calculated per cohort. |
|
|
| OG002 |
| Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 |
Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
|
|
Patients in Dose Escalation Level B1 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
|
|
| OG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
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Patients in Dose Escalation Level B1 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
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Patients in Dose Escalation Level B1 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG002 | Dose Escalation Level B4: 100MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B4 received 100 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG003 | Dose Escalation Level B6: 175MG/M2 GEMCITABINE D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) QD D2-3, 9-10 | Patients in Dose Escalation Level B6 received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO QD on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
| OG004 | Dose Escalation Level 1ESC: 175MG/M2 GEM D1, 8 + 20MG BAY 1895344 (ELIMUSERTIB) BID D2-3, 9-10 | Patients in Dose Escalation Level 1ESC received 175 mg/m2 gemcitabine IV over 30 minutes on days 1 and 8 and 20mg elimusertib PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial. PK samples were collected Days 1, 2, and 8 of Cycle 1. Streck cfDNA tube collections were done at Pre-Study visit. |
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