Castration-resistant Prostate Cancer, Esophageal Adenocarcinoma, Esophageal Squamous Cell Carcinoma, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Head and Neck Squamous Cell Carcinoma, Hepatocellular Carcinoma, Microsatellite Stable Colorectal Cancer, Non-small Cell Lung Cancer, Pancreatic Adenocarcinoma, Renal Cell Carcinoma, Small-cell Lung Cancer, Triple Negative Breast Cancer, Urothelial Carcinoma
Conditions
Keywords
GEJ adenocarcinoma, TNBC, MSS mCRC, PD-L1 + gastric cancer, PD-L1 positive gastric cancer, NSCLC, SCLC, newly diagnosed stage IV pancreatic adenocarcinoma, HCC, RCC, HNSCC, Transitional Cell Carcinoma
Brief summary
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
Detailed description
Note: The Phase 2 portion of the study was not initiated.
Interventions
Sponsors
Merck Sharp & Dohme LLC
GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1 - Dose Escalation of 3 different Regimens and Expansion, Phase 2 - Basket Expansion of 3 Cohorts
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Women of childbearing potential must use an acceptable method of contraception Phase 1 Subjects with the the following: * Regimen A and B: * pancreatic adenocarcinoma, * esophageal adenocarcinoma, or esophageal squamous cell carcinoma, or * gastric/gastroesophageal junction adenocarcinoma, or * TNBC, or * prostate cancer, or * colorectal adenocarcinoma, or subjects with tumor types that have progressed after receiving initial treatment benefit rom the last single agent checkpoint inhibitor that is approved for the indication or in combination with standard of care therapy, for example, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, renal cell carcinoma, and hepatocellular carcinoma, etc. * Regimen C: newly diagnosed stage IV pancreatic cancer Phase 2 * Cohort 1: pancreatic cancer. * Cohort 2: colorectal cancer * Cohort 3: gastric/GEJ adenocarcinoma
Exclusion criteria
* History of another malignancy within 2 years prior to first study drug(s) administration, unless the malignancy was treated with curative intent and the likelihood of relapse is \<5% in 2 years * Pregnant or nursing * Known history of testing positive for human immunodeficiency virus (HIV) * Gastrointestinal (GI) tract disease causing the inability to take oral medication. * Positive test for Hepatitis B virus surface antigen (HBsAg) or a and/or positive Hep C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Dose Escalation - Regimens A and B: Tmax of GB1275 | From first dose through 30 days post last dose | Time of maximum observed plasma concentration |
| 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 | From first dose through 30 days post last dose | Maximum observed plasma concentration |
| Phase 1 Dose Escalation - Regimens A and B: Ctrough of GB1275 | From first dose through 30 days post last dose | Trough observed plasma concentration |
| Phase 1 Dose Escalation - Regimens A and B: t1/2 of GB1275 | From first dose through 30 days post last dose | Terminal phase elimination half-life |
| Phase 1 Dose Escalation - Regimens A and B: AUC of GB1275 | From first dose through 30 days post last dose | Area under the plasma concentration-time curve |
| Phase 1 Dose Escalation - Regimens A and B: CL/F of GB1275 | From first dose through 30 days post last dose | Oral clearance |
| Phase 2 - Basket Cohorts 1, 2 and 3: Objective Response Rate (ORR) | 24 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 - Basket Cohorts 1, 2, and 3: Duration of Response (DOR) | 24 months | DOR defined as time from date of objective response to first documented date of disease progression or death |
| Phase 2 - Basket Cohorts 1, 2, and 3: Time to Response (TTR) | 24 months | TTR defined as time from first dose to first date of objective response |
| Phase 2 - Basket Cohorts 1, 2, and 3: Clinical Benefit Rate (CBR) | 6 months | CBR defined as proportion of subjects with confirmed CR, PR, or stable disease (SD) at six months. |
| Phase 2 - Basket Cohorts 1, 2, and 3: Progression Free Survival (PFS) | 24 months | PFS defined as time from first dose to first documented date of disease progression or death. |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Cmax of GB1275 | From first dose through 30 days post last dose | Maximum observed plasma concentration |
| Phase 2 - Basket Cohorts 1, 2, and 3: Overall Survival (OS) | 24 months | OS defined as time from first dose to date of death. |
| 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. | — |
| Phase 2 - Basket Cohorts 1, 2, and 3: Time to Progression (TTP) | 24 months | TTP defined as time from first dose to first documented date of disease progression. |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Ctrough of GB1275 | From first dose through 30 days post last dose | Trough observed plasma concentration |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Tmax of GB1275 | From first dose through 30 days post last dose | Time of maximum observed plasma concentration |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: t1/2 of GB1275 | From first dose through 30 days post last dose | Terminal phase elimination half-life |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: AUC of GB1275 | From first dose through 30 days post last dose | Area under the plasma concentration-time curve |
| Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: CL/F of GB1275 | From first dose through 30 days post last dose | Oral clearance |
| Phase 1 - Regimen C: Cmax of nab-paclitaxel and gemcitabine | From first dose through 30 days post last dose | Maximum observed plasma concentration |
| Phase 1 - Regimen C: Tmax of nab-paclitaxel and gemcitabine) | From first dose through 30 days post last dose | Time of maximum observed plasma concentration |
| Phase 1 - Regimen C: AUC of nab-paclitaxel and gemcitabine | From first dose through 30 days post last dose | Area under the plasma concentration-time curve |
Countries
United Kingdom, United States
Outcome results
None listed