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

Phase 1

Terminated

• Conditions: Pancreatic Adenocarcinoma; Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Triple Negative Breast Cancer; Castration-resistant Prostate Cancer; Microsatellite Stable Colorectal Cancer; Non-small Cell Lung Cancer; Esophageal Squamous Cell Carcinoma; Gastric Adenocarcinoma; Small-cell Lung Cancer
• Interventions: Drug: GB1275; Drug: nab-paclitaxel and gemcitabine; Drug: pembrolizumab

• Registration Number: NCT04060342
• Lead Sponsor: GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

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.

Study Timeline

• Study First Submitted: 2019-08-09
• Study Start: 2019-08-13
• Study First Submitted QC: 2019-08-14
• Study First Posted: 2019-08-19
• Primary Completion: 2022-04-11
• Study Completion: 2022-04-11
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-17
• Last Update Posted: 2022-08-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 61

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

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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/exclusion criteria will apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1: Regimen A - GB1275 monotherapy	GB1275	GB1275 Monotherapy dose escalation: Oral administration. Twice per day (BID).
Phase 1: Regimen B - GB1275 with an Anti-PD-1	GB1275	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)	GB1275	GB1275 with SOC dose escalation: GB1275 oral administration; twice per day (BID), and nab-paclitaxel and gemcitabine per United States Prescribing Information (USPI)
Phase 1: Regimen C - GB1275 with Standard of Care (SOC)	nab-paclitaxel and gemcitabine	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	GB1275	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	GB1275	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).
Phase 2: Cohort 3 - GB1275 with an Anti-PD-1	GB1275	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).
Phase 2: Cohort 1 - GB1275 with SOC	nab-paclitaxel and gemcitabine	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 1: Regimen B - GB1275 with an Anti-PD-1	pembrolizumab	GB1275 with pembrolizumab dose escalation and expansion: GB1275 oral administration; twice per day (BID), and pembrolizumab IV administration once every 3 weeks (Q3W).
Phase 2: Cohort 2 - GB1275 with an Anti-PD-1	pembrolizumab	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).
Phase 2: Cohort 3 - GB1275 with an Anti-PD-1	pembrolizumab	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).

Primary Outcome Measures

Name	Time	Method
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: 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: 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: 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

Name	Time	Method
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 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 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.

Trial Locations

Locations (8)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

South Texas Accelerated Research Therapeutics, LLC; 🇺🇸 San Antonio, Texas, United States

The Royals Marsden NHS Foundation Trust; 🇬🇧 Sutton, Surrey, United Kingdom

UCSF Medical Center at Mission Bay; 🇺🇸 San Francisco, California, United States

Washington University School of Medicine - Siteman Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

University of Colorado Hospital, Anschutz Cancer Pavilion (ACP); 🇺🇸 Aurora, Colorado, United States

The Sarah Cannon Research Institute/Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States