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

• ClinicalTrials.gov Identifier: NCT04060342
• Recruitment Status: Terminated
• First Posted: August 19, 2019
• Last Update Posted: August 18, 2022
• Sponsor: GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Gossamer Bio Inc. ( GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. )

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
Pancreatic Adenocarcinoma; Esophageal Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Triple Negative Breast Cancer; Castration-resistant Prostate Cancer; Microsatellite Stable Colorectal Cancer; Non-small Cell Lung Cancer; Small-cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Urothelial Carcinoma; Renal Cell Carcinoma; Hepatocellular Carcinoma	Drug: GB1275; Drug: nab-paclitaxel and gemcitabine; Drug: pembrolizumab	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Phase 1 - Dose Escalation of 3 different Regimens and Expansion, Phase 2 - Basket Expansion of 3 Cohorts
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 13, 2019
• Actual Primary Completion Date: April 11, 2022
• Actual Study Completion Date: April 11, 2022

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 Name: 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: GB1275; Oral; Other Name: Investigational; Drug: pembrolizumab; IV infusion; Other Name: Anti-PD-1
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 Name: Investigational; Drug: nab-paclitaxel and gemcitabine; IV infusion; Other Name: 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 Name: Investigational; Drug: nab-paclitaxel and gemcitabine; IV infusion; Other Name: 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: GB1275; Oral; Other Name: Investigational; Drug: pembrolizumab; IV infusion; Other Name: Anti-PD-1
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 Name: Investigational; Drug: pembrolizumab; IV infusion; Other Name: Anti-PD-1

Outcome Measures

Primary Outcome Measures :

1. Phase 1 Dose Escalation - Regimens A, B,and C: Incidence of dose limiting toxicities (DLTs) [ Time Frame: Regimen A and B dose escalation Days 1-21, Regimen C dose escalation Days 8-36 days ]
2. Phase 1 Dose Escalation - Regimens A, B, and C and Phase 1 Expansion - Regimen B: Incidence of adverse events (AEs) [ Time Frame: Regimen A and C from first dose through 30 days post last dose, Regimen B from first dose through 90 days post last dose ]
3. Phase 1 Dose Escalation - Regimens A and B: Cmax of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Maximum observed plasma concentration
4. Phase 1 Dose Escalation - Regimens A and B: Ctrough of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Trough observed plasma concentration
5. Phase 1 Dose Escalation - Regimens A and B: Tmax of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Time of maximum observed plasma concentration
6. Phase 1 Dose Escalation - Regimens A and B: t1/2 of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Terminal phase elimination half-life
7. Phase 1 Dose Escalation - Regimens A and B: AUC of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Area under the plasma concentration-time curve
8. Phase 1 Dose Escalation - Regimens A and B: CL/F of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Oral clearance
9. Phase 2 - Basket Cohorts 1, 2 and 3: Objective Response Rate (ORR) [ Time Frame: 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 :

1. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Cmax of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Maximum observed plasma concentration
2. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Ctrough of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Trough observed plasma concentration
3. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Tmax of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Time of maximum observed plasma concentration
4. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: t1/2 of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Terminal phase elimination half-life
5. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: AUC of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Area under the plasma concentration-time curve
6. Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: CL/F of GB1275 [ Time Frame: From first dose through 30 days post last dose ]
   Oral clearance
7. Phase 1 - Regimen C: Cmax of nab-paclitaxel and gemcitabine [ Time Frame: From first dose through 30 days post last dose ]
   Maximum observed plasma concentration
8. Phase 1 - Regimen C: Tmax of nab-paclitaxel and gemcitabine) [ Time Frame: From first dose through 30 days post last dose ]
   Time of maximum observed plasma concentration
9. Phase 1 - Regimen C: AUC of nab-paclitaxel and gemcitabine [ Time Frame: From first dose through 30 days post last dose ]
   Area under the plasma concentration-time curve
10. Phase 2 - Basket Cohorts 1, 2, and 3: Duration of Response (DOR) [ Time Frame: 24 months ]
    DOR defined as time from date of objective response to first documented date of disease progression or death
11. Phase 2 - Basket Cohorts 1, 2, and 3: Time to Response (TTR) [ Time Frame: 24 months ]
    TTR defined as time from first dose to first date of objective response
12. Phase 2 - Basket Cohorts 1, 2, and 3: Clinical Benefit Rate (CBR) [ Time Frame: 6 months ]
    CBR defined as proportion of subjects with confirmed CR, PR, or stable disease (SD) at six months.
13. Phase 2 - Basket Cohorts 1, 2, and 3: Progression Free Survival (PFS) [ Time Frame: 24 months ]
    PFS defined as time from first dose to first documented date of disease progression or death.
14. Phase 2 - Basket Cohorts 1, 2, and 3: Time to Progression (TTP) [ Time Frame: 24 months ]
    TTP defined as time from first dose to first documented date of disease progression.
15. Phase 2 - Basket Cohorts 1, 2, and 3: Overall Survival (OS) [ Time Frame: 24 months ]
    OS defined as time from first dose to date of death.
16. Phase 2 - Basket Cohorts 1, 2, and 3: Incidence of AEs [ Time Frame: 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. ]
17. Phase 2 - Basket Cohort 1, 2 and 3: PK profile of GB1275 [ Time Frame: Basket Cohorts 1, 2, and 3 from first dose through 30 days post last dose. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.
• 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

Contacts and Locations

Locations

United States, California

UCSF Medical Center at Mission Bay

San Francisco, California, United States, 94158

United States, Colorado

University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, United States, 80045

United States, Missouri

Washington University School of Medicine - Siteman Cancer Center

Saint Louis, Missouri, United States, 63110

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Tennessee

The Sarah Cannon Research Institute/Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Texas

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, United States, 78229

United Kingdom

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

More Information

• Responsible Party: GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
• ClinicalTrials.gov Identifier: NCT04060342
• Other Study ID Numbers: GB1275-1101 (KEYNOTE-A36)
• First Posted: August 19, 2019
• Last Update Posted: August 18, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gossamer Bio Inc. ( GB006, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. ):

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

Additional relevant MeSH terms:

Carcinoma; Lung Neoplasms; Carcinoma, Squamous Cell; Adenocarcinoma; Small Cell Lung Carcinoma; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Squamous Cell; Breast Neoplasms; Breast Diseases; Skin Diseases; Head and Neck Neoplasms; Esophageal Neoplasms; Esophageal Diseases; Paclitaxel