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

NCT04060342 | Terminated Phase 1 FDA Drug

• 1 other identifier: GB1275-1101 (KEYNOTE-A36)
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 8

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

Conditions

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

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

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (17)

• Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Cmax of GB1275

  From first dose through 30 days post last dose

• Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Ctrough of GB1275

  From first dose through 30 days post last dose

• Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: Tmax of GB1275

  From first dose through 30 days post last dose

• Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: t1/2 of GB1275

  From first dose through 30 days post last dose

• Phase 1 - Regimen C and Phase 1 Expansion - Regimen B: AUC of GB1275

  From first dose through 30 days post last dose

Study Arms (6)

Phase 1: Regimen A - GB1275 monotherapy

EXPERIMENTAL

GB1275 Monotherapy dose escalation: Oral administration. Twice per day (BID).

Drug: GB1275

Phase 1: Regimen B - GB1275 with an Anti-PD-1

EXPERIMENTAL

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; Drug: pembrolizumab

Phase 1: Regimen C - GB1275 with Standard of Care (SOC)

EXPERIMENTAL

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; Drug: nab-paclitaxel and gemcitabine

Phase 2: Cohort 1 - GB1275 with SOC

EXPERIMENTAL

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; Drug: nab-paclitaxel and gemcitabine

Phase 2: Cohort 2 - GB1275 with an Anti-PD-1

EXPERIMENTAL

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; Drug: pembrolizumab

Phase 2: Cohort 3 - GB1275 with an Anti-PD-1

EXPERIMENTAL

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; Drug: pembrolizumab

Interventions

GB1275 DRUG

Oral

Also known as: Investigational

Phase 1: Regimen A - GB1275 monotherapy; Phase 1: Regimen B - GB1275 with an Anti-PD-1; Phase 1: Regimen C - GB1275 with Standard of Care (SOC); Phase 2: Cohort 1 - GB1275 with SOC; Phase 2: Cohort 2 - GB1275 with an Anti-PD-1; Phase 2: Cohort 3 - GB1275 with an Anti-PD-1

nab-paclitaxel and gemcitabine DRUG

IV infusion

Also known as: Abraxane and Gemzar

Phase 1: Regimen C - GB1275 with Standard of Care (SOC); Phase 2: Cohort 1 - GB1275 with SOC

pembrolizumab DRUG

IV infusion

Also known as: Anti-PD-1

Phase 1: Regimen B - GB1275 with an Anti-PD-1; Phase 2: Cohort 2 - GB1275 with an Anti-PD-1; Phase 2: Cohort 3 - GB1275 with an Anti-PD-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (8)

UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, 80045, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Sarah Cannon Research Institute/Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

The Royals Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Transitional Cell; Carcinoma, Renal Cell; Carcinoma, Hepatocellular; Stomach Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Gemcitabine; Albumin-Bound Paclitaxel; pembrolizumab; spartalizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Liver Neoplasms; Liver Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 - Dose Escalation of 3 different Regimens and Expansion, Phase 2 - Basket Expansion of 3 Cohorts

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: August 19, 2019
• Study Start: August 13, 2019
• Primary Completion: April 11, 2022
• Study Completion: April 11, 2022
• Last Updated: August 18, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); GB (1)