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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2016-01594 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| Winship3321-16 | Other Identifier | Emory University/Winship Cancer Institute | |
| P30CA138292 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| Exelixis | INDUSTRY |
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) |
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This phase Ib trial studies the side effects and best dose of Hsp90 inhibitor XL888 when given together with pembrolizumab in treating patients with advanced gastrointestinal cancer that has spread to other places in the body. XL888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving XL888 with pembrolizumab may work better in treating patients with gastrointestinal cancer.
PRIMARY OBJECTIVE:
I. Determine the recommended phase II dose for the combination of XL888 and pembrolizumab.
SECONDARY OBJECTIVES:
I. Define the toxicity profile of the combination of XL888 and pembrolizumab.
II. Evaluate the activity of the combination of XL888 and pembrolizumab in previously treated patients with gastrointestinal tumors.
TERTIARY OBJECTIVE:
I. Evaluate the effect of the combination on the immune profile in the serum and in tumor biopsies.
OUTLINE: This is a dose-escalation study of Hsp90 inhibitor XL888.
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and XL888 orally (PO) on day 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and periodically thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation | Experimental | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| Dose Expansion Pancreatic Cancer (Arm A) | Experimental | In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
|
| Dose Expansion Colorectal Cancer (Arm B) | Experimental | In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XL888 | Drug | Given PO |
|
| Measure | Description | Time Frame |
|---|---|---|
| Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Summary statistics will be presented. Toxicities will be presented as worst toxicity per patient. | Cycle length 21 days. Outcome determined on day 22 (after completion of cycle 1) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | RECIST version 1.1 will be used in this study for assessment of tumor response. While either CT or MRI may be utilized, as per RECIST 1.1, CT is the preferred imaging technique in this study. | Up to 2 years after cycle 1, day 1. Cycle length is 21 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15 | Change in cytokine and chemokine concentrations from Cycle 1 Day 1 (baseline) to Cycle 1 Day 15, calculated as the within-subject difference (Day 15 minus Day 1). Immune mediators assessed included Eotaxin, Fractalkine, G-CSF, GM-CSF, IL-1RA, IL-4, IL-6, IL-9, IL-13, IL-15, IP-10, MCP-1, MCP-3, M-CSF, and MDC. Positive values indicate an increase from baseline, and negative values indicate a decrease from baseline. |
Inclusion Criteria:
Patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, gastroesophageal junction [GEJ], cholangiocarcinoma, hepatocellular, pancreas, colorectal, small intestinal tumors) who have failed at least one prior therapy (dose escalation phase)
Patients with pancreatic adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen; eight patients must have tumors that are accessible for biopsy and sign the informed consent for paired biopsy study (dose escalation phase, arm A)
Patients with colorectal adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and fluoropyrimidine; eight patients must have tumors that are accessible for biopsy and sign the informed consent for paired biopsy study (dose escalation phase, arm B)
Be willing and able to provide written informed consent/assent for the trial
Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Absolute neutrophil count (ANC) ≥ 1,500 cells/µL
Platelets ≥ 100,000 cells/µL
Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) ≥ 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
Serum total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x ULN OR ≤ 5 x ULN for subjects with liver metastases
Albumin ≥ 2.5 mg/dL
International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
Exclusion Criteria:
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Has a known history of active tuberculosis (TB) (Bacillus tuberculosis)
Hypersensitivity to pembrolizumab or history of severe allergic or hypersensitivity reactions to excipients (e.g., polyethylene glycol [PEG] 300 and polysorbate 80)
Clinically significant cardiovascular disease or peripheral vascular (e.g. myocardial infarction, unstable angina within 6 months of study entry), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia requiring medications, baseline corrected QT (QTc) > 450 msec or previous history of QT prolongation while taking other medications
Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent
Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Has known history of, or any evidence of active, non-infectious pneumonitis
Has an active infection requiring systemic therapy
Has known substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1, or anti-PD-L2 agent
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has known active hepatitis B (e.g., hepatitis surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
Has received a live vaccine within 30 days of planned start of study therapy
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| Name | Affiliation | Role |
|---|---|---|
| Maria Diab, MD | Emory University/Winship Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University Hospital Midtown | Atlanta | Georgia | 30308 | United States | ||
| Emory University/Winship Cancer Institute |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Expansion Pancreatic Cancer (Arm A) | In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| 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 | Jun 13, 2023 |
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| NIH |
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|
| Pembrolizumab | Biological | Given IV |
|
|
| Overall Survival | Once a subject experiences confirmed disease progression or starts a new anti-cancer therapy, the subject moves into the survival follow-up phase and should be contacted by telephone every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of the study, whichever occurs first. | Up to 1 year after cycle 1, day 1. Each cycle is 21 days. |
| Progression Free Survival | Summary statistics will be presented. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Up to 6 months after cycle 1, day 1. Each cycle is 21 days |
| Response Duration as Assessed by RECIST 1.1 | Summary statistics will be presented. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Up to 2 years after cycle 1, day 1. Each cycle is 21 days. |
| Up to 2 years after cycle 1, day 1. Each cycle is 21 days. |
| Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15 | Change in peripheral blood immune cell subset percentages from Cycle 1 Day 1 (baseline) to Cycle 1 Day 15, calculated as the within-subject difference (Day 15 minus Day 1). Immune cell subsets were assessed using the Maxpar Direct Immune Profiling Assay (MDIPA) and included lymphocyte, T-cell, B-cell, natural killer (NK) cell, monocyte, and dendritic cell populations, including naïve, central memory, effector memory, terminal effector, regulatory T-cell, helper T-cell polarization, γδ T-cell, and MAIT/NKT-like subsets. Positive values indicate an increase from baseline, and negative values indicate a decrease from baseline. | Up to 2 years after cycle 1, day 1. Each cycle is 21 days. |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| Emory Saint Joseph's Hospital | Atlanta | Georgia | 30342 | United States |
| FG001 | Dose Expansion Colorectal Cancer (Arm B) | In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. XL888: Given PO Pembrolizumab: Given IV |
| FG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| FG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| FG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Expansion Pancreatic Cancer (Arm A) | In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| BG001 | Dose Expansion Colorectal Cancer (Arm B) | In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. XL888: Given PO Pembrolizumab: Given IV |
| BG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| BG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| BG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| 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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| Age, Continuous | Median | Inter-Quartile Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | 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 | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Summary statistics will be presented. Toxicities will be presented as worst toxicity per patient. | Posted | Count of Participants | Participants | Cycle length 21 days. Outcome determined on day 22 (after completion of cycle 1) |
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| Secondary | Overall Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | RECIST version 1.1 will be used in this study for assessment of tumor response. While either CT or MRI may be utilized, as per RECIST 1.1, CT is the preferred imaging technique in this study. | Posted | Number | Percentage of participants | Up to 2 years after cycle 1, day 1. Cycle length is 21 days. |
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival | Once a subject experiences confirmed disease progression or starts a new anti-cancer therapy, the subject moves into the survival follow-up phase and should be contacted by telephone every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of the study, whichever occurs first. | Posted | Median | 95% Confidence Interval | Months | Up to 1 year after cycle 1, day 1. Each cycle is 21 days. |
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| Secondary | Progression Free Survival | Summary statistics will be presented. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Posted | Median | 95% Confidence Interval | Months | Up to 6 months after cycle 1, day 1. Each cycle is 21 days |
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| Secondary | Response Duration as Assessed by RECIST 1.1 | Summary statistics will be presented. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Posted | Median | 95% Confidence Interval | Months | Up to 2 years after cycle 1, day 1. Each cycle is 21 days. |
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| Other Pre-specified | Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15 | Change in cytokine and chemokine concentrations from Cycle 1 Day 1 (baseline) to Cycle 1 Day 15, calculated as the within-subject difference (Day 15 minus Day 1). Immune mediators assessed included Eotaxin, Fractalkine, G-CSF, GM-CSF, IL-1RA, IL-4, IL-6, IL-9, IL-13, IL-15, IP-10, MCP-1, MCP-3, M-CSF, and MDC. Positive values indicate an increase from baseline, and negative values indicate a decrease from baseline. | Blood samples failed quality control during testing therefore the specimen for the missing patients were not testable. | Posted | Mean | Standard Deviation | pg/mL | Up to 2 years after cycle 1, day 1. Each cycle is 21 days. |
| |||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15 | Change in peripheral blood immune cell subset percentages from Cycle 1 Day 1 (baseline) to Cycle 1 Day 15, calculated as the within-subject difference (Day 15 minus Day 1). Immune cell subsets were assessed using the Maxpar Direct Immune Profiling Assay (MDIPA) and included lymphocyte, T-cell, B-cell, natural killer (NK) cell, monocyte, and dendritic cell populations, including naïve, central memory, effector memory, terminal effector, regulatory T-cell, helper T-cell polarization, γδ T-cell, and MAIT/NKT-like subsets. Positive values indicate an increase from baseline, and negative values indicate a decrease from baseline. | Blood samples failed quality control during testing therefore the specimen for the missing patients were not testable. | Posted | Mean | Standard Deviation | Percentage points | Up to 2 years after cycle 1, day 1. Each cycle is 21 days. |
|
Up to 1 year after cycle 1, day 1
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Expansion Pancreatic Cancer (Arm A) | In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV | 1 | 17 | 5 | 17 | 0 | 17 |
| EG001 | Dose Expansion Pancreatic Cancer (Arm B) | In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. XL888: Given PO Pembrolizumab: Given IV | 1 | 16 | 7 | 16 | 1 | 16 |
| EG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV | 0 | 3 | 0 | 3 | 0 | 3 |
| EG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV | 0 | 3 | 0 | 3 | 0 | 3 |
| EG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV | 0 | 8 | 2 | 8 | 1 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| General disorders and administration site conditions - Other, specify | General disorders | Non-systematic Assessment |
| ||
| Stroke | Nervous system disorders | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Non-systematic Assessment |
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| Periorbital edema | Eye disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Fever | General disorders | Non-systematic Assessment |
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| Chills | General disorders | Non-systematic Assessment |
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| Pelvic infection | Infections and infestations | Non-systematic Assessment |
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| Hypertension | Vascular disorders | Non-systematic Assessment |
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| Blood and lymphatic system disorders - Other, specify | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Tooth infection | Infections and infestations | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Paresthesia | Nervous system disorders | Non-systematic Assessment |
| ||
| Retinopathy | Eye disorders | Non-systematic Assessment |
| ||
| Autoimmune disorder | Immune system disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Non-systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Non-systematic Assessment |
|
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Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Olatunji Alese | Emory University | 4047781900 | olatunji.alese@emory.edu |
| Aug 4, 2025 |
| Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 20, 2021 | Apr 28, 2023 | ICF_000.pdf |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C559121 | XL 888 |
| C582435 | pembrolizumab |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Blood and lymphatic system disorders |
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| Cardiac disorders |
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| Ear and labyrinth disorders |
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| Endocrine disorders |
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| Eye disorders |
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| Gastrointestinal disorders |
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| General disorders and administration site conditions |
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| Hepatobiliary disorders |
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| Immune system disorders |
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| Infections and infestations |
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| Injury, poisoning and procedural complications |
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| Investigations |
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| Metabolism and nutrition disorders |
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| Musculoskeletal and connective tissue disorders |
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| Nervous system disorders |
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| Psychiatric disorders |
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| Renal and urinary disorders |
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| Respiratory, thoracic and mediastinal disorders |
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| Skin and subcutaneous tissue disorders |
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| Social circumstances |
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| Vascular disorders |
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| OG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
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| OG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
|
|
| OG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
|
|
| OG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
|
|
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
| OG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
|
|
| OG001 | Dose Expansion Colorectal Cancer (Arm B) | In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy. XL888: Given PO Pembrolizumab: Given IV |
| OG002 | Dose Escalation 45 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG003 | Dose Escalation 60 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
| OG004 | Dose Escalation 90 mg PO Twice Weekly | In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. XL888: Given PO Pembrolizumab: Given IV |
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