GB1275 Monotherapy and in Combination With an Anti-PD1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma
Study Details
Study Description
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
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
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Phase 1 |
Detailed Description
Note: The Phase 2 portion of the study was not initiated.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Phase 1: Regimen A - GB1275 monotherapy GB1275 Monotherapy dose escalation: Oral administration. Twice per day (BID). |
Drug: GB1275
Oral
Other Names:
|
Experimental: Phase 1: Regimen B - GB1275 with an Anti-PD-1 GB1275 with pembrolizumab dose escalation and expansion: GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W). |
Drug: GB1275
Oral
Other Names:
Drug: pembrolizumab
IV infusion
Other Names:
|
Experimental: Phase 1: Regimen C - GB1275 with Standard of Care (SOC) GB1275 with SOC dose escalation: GB1275 oral administration; twice per day (BID), and nab-paclitaxel and gemcitabine per United States Prescribing Information (USPI) |
Drug: GB1275
Oral
Other Names:
Drug: nab-paclitaxel and gemcitabine
IV infusion
Other Names:
|
Experimental: Phase 2: Cohort 1 - GB1275 with SOC 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. |
Drug: GB1275
Oral
Other Names:
Drug: nab-paclitaxel and gemcitabine
IV infusion
Other Names:
|
Experimental: Phase 2: Cohort 2 - GB1275 with an Anti-PD-1 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). |
Drug: GB1275
Oral
Other Names:
Drug: pembrolizumab
IV infusion
Other Names:
|
Experimental: Phase 2: Cohort 3 - GB1275 with an Anti-PD-1 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). |
Drug: GB1275
Oral
Other Names:
Drug: pembrolizumab
IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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: Tmax of GB1275 [From first dose through 30 days post last dose]
Time of maximum 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 Outcome Measures
- 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 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
- 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 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 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.]
Eligibility Criteria
Criteria
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.
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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
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Pregnant or nursing
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Known history of testing positive for human immunodeficiency virus (HIV)
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Gastrointestinal (GI) tract disease causing the inability to take oral medication.
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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/exclusion criteria will apply
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UCSF Medical Center at Mission Bay | San Francisco | California | United States | 94158 |
2 | University of Colorado Hospital, Anschutz Cancer Pavilion (ACP) | Aurora | Colorado | United States | 80045 |
3 | Washington University School of Medicine - Siteman Cancer Center | Saint Louis | Missouri | United States | 63110 |
4 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
5 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
6 | The Sarah Cannon Research Institute/Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
7 | South Texas Accelerated Research Therapeutics, LLC | San Antonio | Texas | United States | 78229 |
8 | The Royals Marsden NHS Foundation Trust | Sutton | Surrey | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
- Merck Sharp & Dohme LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GB1275-1101 (KEYNOTE-A36)