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 Overview

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

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

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

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

GB1275-1101 (KEYNOTE-A36)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-08-09	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-08-17
First Submitted that Met QC Criteria 2019-08-14	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-08-18
First Posted (ACTUAL) 2019-08-19	Results First Posted N/A	Last Verified 2022-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

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
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 DRUG: pembrolizumab IV infusion
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 DRUG: nab-paclitaxel and gemcitabine IV infusion
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 DRUG: nab-paclitaxel and gemcitabine IV infusion
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 DRUG: pembrolizumab IV infusion
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

Primary Outcome Measures	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	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.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Cohort 1: pancreatic cancer.
Cohort 2: colorectal cancer
Cohort 3: gastric/GEJ adenocarcinoma

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Merck Sharp & Dohme LLC

Investigators

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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Resources

Patients

Caregivers

Clinical Trial Record