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No clear benefit of GB1275 was observed either as monotherapy or in combination with pembrolizumab.
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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This first-in-human (FIH ) study is an open-label, multicenter study that consists of a Phase 1 Dose Escalation/Expansion phase of GB1275 monotherapy or in combination with Anti-PD-1 Antibody or in combination with Standard of Care in Patients with Metastatic Pancreatic Adenocarcinoma followed by a Phase 2 Basket Expansion phase in Patients with Specified Metastatic Solid Tumors
Note: The Phase 2 portion of the study was not initiated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1: Regimen A - GB1275 monotherapy | Experimental | GB1275 Monotherapy dose escalation: Oral administration. Twice per day (BID). |
|
| Phase 1: Regimen B - GB1275 with an Anti-PD-1 | Experimental | GB1275 with pembrolizumab dose escalation and expansion: GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W). |
|
| Phase 1: Regimen C - GB1275 with Standard of Care (SOC) | Experimental | GB1275 with SOC dose escalation: GB1275 oral administration; twice per day (BID), and nab-paclitaxel and gemcitabine per United States Prescribing Information (USPI) |
|
| Phase 2: Cohort 1 - GB1275 with SOC | Experimental | GB1275 with SOC Basket Cohort in patients with newly diagnosed metastatic pancreatic cancer: GB1275 oral administration; twice per day (BID) and nab-paclitaxel and gemcitabine per USPI. |
|
| Phase 2: Cohort 2 - GB1275 with an Anti-PD-1 | Experimental | GB1275 with pembrolizumab Basket Cohort in patients with MSS colorectal cancer: GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GB1275 | Drug | Oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 Dose Escalation - Regimens A, B,and C: Incidence of dose limiting toxicities (DLTs) | Regimen A and B dose escalation Days 1-21, Regimen C dose escalation Days 8-36 days | |
| Phase 1 Dose Escalation - Regimens A, B, and C and Phase 1 Expansion - Regimen B: Incidence of adverse events (AEs) | Regimen A and C from first dose through 30 days post last dose, Regimen B from first dose through 90 days post last dose | |
| Phase 1 Dose Escalation - Regimens A and B: Cmax of GB1275 | Maximum observed plasma concentration | From first dose through 30 days post last dose |
| Phase 1 Dose Escalation - Regimens A and B: Ctrough of GB1275 | Trough observed plasma concentration | From first dose through 30 days post last dose |
| Phase 1 Dose Escalation - Regimens A and B: Tmax of GB1275 | Time of maximum observed plasma concentration | From first dose through 30 days post last dose |
| Phase 1 Dose Escalation - Regimens A and B: t1/2 of GB1275 | Terminal phase elimination half-life | From first dose through 30 days post last dose |
| Phase 1 Dose Escalation - Regimens A and B: AUC of GB1275 | Area under the plasma concentration-time curve | From first dose through 30 days post last dose |
| Phase 1 Dose Escalation - Regimens A and B: CL/F of GB1275 |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Cmax of GB1275 | Maximum observed plasma concentration | From first dose through 30 days post last dose |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Ctrough of GB1275 |
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Inclusion Criteria:
Phase 1
Subjects with the the following:
Regimen A and B:
Regimen C: newly diagnosed stage IV pancreatic cancer
Phase 2
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria will apply
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Medical Center at Mission Bay | San Francisco | California | 94158 | United States | ||
| University of Colorado Hospital, Anschutz Cancer Pavilion (ACP) |
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Phase 1 - Dose Escalation of 3 different Regimens and Expansion, Phase 2 - Basket Expansion of 3 Cohorts
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|
| Phase 2: Cohort 3 - GB1275 with an Anti-PD-1 | Experimental | GB1275 with pembrolizumab Basket Cohort in patients with gastric/GEJ cancer, PD-L1 positive: GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W). |
|
|
| nab-paclitaxel and gemcitabine | Drug | IV infusion |
|
|
| pembrolizumab | Drug | IV infusion |
|
|
Oral clearance |
| From first dose through 30 days post last dose |
| Phase 2 - Basket Cohorts 1, 2 and 3: Objective Response Rate (ORR) | ORR defined as the proportion of subjects with best overall confirmed response (BOCR) of either a complete response (CR) or partial response (PR) as assessed by the Investigator based on RECIST v1.1 | 24 months |
Trough observed plasma concentration
| From first dose through 30 days post last dose |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Tmax of GB1275 | Time of maximum observed plasma concentration | From first dose through 30 days post last dose |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: t1/2 of GB1275 | Terminal phase elimination half-life | From first dose through 30 days post last dose |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: AUC of GB1275 | Area under the plasma concentration-time curve | From first dose through 30 days post last dose |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: CL/F of GB1275 | Oral clearance | From first dose through 30 days post last dose |
| Phase 1 - Regimen C: Cmax of nab-paclitaxel and gemcitabine | Maximum observed plasma concentration | From first dose through 30 days post last dose |
| Phase 1 - Regimen C: Tmax of nab-paclitaxel and gemcitabine) | Time of maximum observed plasma concentration | From first dose through 30 days post last dose |
| Phase 1 - Regimen C: AUC of nab-paclitaxel and gemcitabine | Area under the plasma concentration-time curve | From first dose through 30 days post last dose |
| Phase 2 - Basket Cohorts 1, 2, and 3: Duration of Response (DOR) | DOR defined as time from date of objective response to first documented date of disease progression or death | 24 months |
| Phase 2 - Basket Cohorts 1, 2, and 3: Time to Response (TTR) | TTR defined as time from first dose to first date of objective response | 24 months |
| Phase 2 - Basket Cohorts 1, 2, and 3: Clinical Benefit Rate (CBR) | CBR defined as proportion of subjects with confirmed CR, PR, or stable disease (SD) at six months. | 6 months |
| Phase 2 - Basket Cohorts 1, 2, and 3: Progression Free Survival (PFS) | PFS defined as time from first dose to first documented date of disease progression or death. | 24 months |
| Phase 2 - Basket Cohorts 1, 2, and 3: Time to Progression (TTP) | TTP defined as time from first dose to first documented date of disease progression. | 24 months |
| Phase 2 - Basket Cohorts 1, 2, and 3: Overall Survival (OS) | OS defined as time from first dose to date of death. | 24 months |
| Phase 2 - Basket Cohorts 1, 2, and 3: Incidence of AEs | Basket Cohorts 1 from first dose through 30 days post last dose, Basket Cohorts 2 and 3 from first dose through 90 days post last dose. |
| Phase 2 - Basket Cohort 1, 2 and 3: PK profile of GB1275 | Basket Cohorts 1, 2, and 3 from first dose through 30 days post last dose. |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Washington University School of Medicine - Siteman Cancer Center | St Louis | Missouri | 63110 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| The Sarah Cannon Research Institute/Tennessee Oncology | Nashville | Tennessee | 37203 | United States |
| South Texas Accelerated Research Therapeutics, LLC | San Antonio | Texas | 78229 | United States |
| The Royals Marsden NHS Foundation Trust | Sutton | Surrey | SM2 5PT | United Kingdom |
| ID | Term |
|---|---|
| C562730 | Adenocarcinoma Of Esophagus |
| D000077277 | Esophageal Squamous Cell Carcinoma |
| D064726 | Triple Negative Breast Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D055752 | Small Cell Lung Carcinoma |
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D002295 | Carcinoma, Transitional Cell |
| D002292 | Carcinoma, Renal Cell |
| D006528 | Carcinoma, Hepatocellular |
| D013274 | Stomach Neoplasms |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018307 | Neoplasms, Squamous Cell |
| D004938 | Esophageal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D001943 | Breast Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000230 | Adenocarcinoma |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D008113 | Liver Neoplasms |
| D008107 | Liver Diseases |
| D013272 | Stomach Diseases |
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| ID | Term |
|---|---|
| C520255 | 130-nm albumin-bound paclitaxel |
| D000093542 | Gemcitabine |
| D000068196 | Albumin-Bound Paclitaxel |
| C582435 | pembrolizumab |
| C000711728 | spartalizumab |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017239 | Paclitaxel |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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