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

A Phase 1/2, First-in-Human, Open-label, Dose Escalation Study of GB1275 Monotherapy and in Combination With an Anti-PD-1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma, Followed by Basket Expansion of GB1275 With Standard of Care or in Combination With an Anti-PD-1 Antibody in Patients With Specified Metastatic Solid Tumors

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

Study Overview

• Status: Terminated
• Conditions: Renal Cell Carcinoma; Hepatocellular Carcinoma; Pancreatic Adenocarcinoma; Gastric Adenocarcinoma; Triple Negative Breast Cancer; Non-small Cell Lung Cancer; Small-cell Lung Cancer; Castration-resistant Prostate Cancer; Head and Neck Squamous Cell Carcinoma; Esophageal Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Urothelial Carcinoma; Gastroesophageal Junction Adenocarcinoma; Microsatellite Stable Colorectal Cancer
• Intervention / Treatment: Drug: pembrolizumab; Drug: GB1275; Drug: nab-paclitaxel and gemcitabine

Detailed Description

Note: The Phase 2 portion of the study was not initiated.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • The Royals Marsden NHS Foundation Trust
• United States
  • California
    • San Francisco, California, United States, 94158
      • UCSF Medical Center at Mission Bay
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Siteman Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute/Tennessee Oncology
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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/exclusion criteria will apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / 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: Investigational
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: pembrolizumab; IV infusion; Other Names: Anti-PD-1; Drug: GB1275; Oral; Other Names: Investigational
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: Investigational; Drug: nab-paclitaxel and gemcitabine; IV infusion; Other Names: Abraxane and Gemzar
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: Investigational; Drug: nab-paclitaxel and gemcitabine; IV infusion; Other Names: Abraxane and Gemzar
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: pembrolizumab; IV infusion; Other Names: Anti-PD-1; Drug: GB1275; Oral; Other Names: Investigational
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: pembrolizumab; IV infusion; Other Names: Anti-PD-1; Drug: GB1275; Oral; Other Names: Investigational

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Secondary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2019
• Primary Completion (Actual): April 11, 2022
• Study Completion (Actual): April 11, 2022

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 14, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: NSCLC; HCC; TNBC; HNSCC; SCLC; Transitional Cell Carcinoma; RCC; GEJ adenocarcinoma; MSS mCRC; PD-L1 + gastric cancer; PD-L1 positive gastric cancer; newly diagnosed stage IV pancreatic adenocarcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Breast Neoplasms; Lung Neoplasms; Carcinoma; Adenocarcinoma; Small Cell Lung Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Gemcitabine; Paclitaxel; Pembrolizumab
• Other Study ID Numbers: GB1275-1101 (KEYNOTE-A36)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No