Paclitaxel, Pembrolizumab and Olaparib in Previously Treated Advanced Gastric Adenocarcinoma

Phase 2 Study of Paclitaxel, Pembrolizumab and Olaparib in Previously Treated Advanced Gastric Adenocarcinoma

The purpose of this study is to evaluate the safety and clinical activity of paclitaxel plus olaparib and pembrolizumab in patients with previously treated advanced Gastric Cancer (GC).

Study Overview

• Status: Completed
• Conditions: Advanced Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Paclitaxel; Drug: Olaparib; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Must have advanced gastric or gastroesophageal cancer.
• Must have received only one prior line of systemic therapy for advanced disease and experienced disease progression on this regimen..
• For Cohort 1: Must have the presence of measurable lesion.
• Must agree to have a biopsy.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study - specified laboratory tests.
• Woman of childbearing potential must have a negative pregnancy test.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Require any antineoplastic therapy.
• Require any other form of systemic or localized antineoplastic therapy.
• Has received prior therapy with paclitaxel or PARP inhibitor. Previous paclitaxel may be allowed if no progression on or within 6 months of receiving this drug.
• Hypersensitivity reaction to any paclitaxel, pembrolizumab or related compounds and/or to any of the components.
• Allergy to dexamethasone, diphenhydramine and famotidine.
• Is taking a moderate or strong CYP3A inhibitor.
• Has uncontrolled intercurrent acute or chronic medical illness.
• Has a known additional malignancy that is progressing and has required active treatment within the past 1 year.
• Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Is currently or has participated in another investigational study within 4 weeks prior to receiving study drug.
• Has an active known or suspected autoimmune disease.
• Has a diagnosis of immunodeficiency.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. .
• Requires daily supplemental oxygen.
• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• History of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Infection with HIV or hepatitis B or C at screening.
• Has uncontrolled infection requiring systemic therapy..
• Subjects unable to undergo venipuncture and/or tolerate venous access.
• Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
• Woman who are pregnant or breastfeeding.
• A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to study drug initiation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Measurable Disease	Drug: Paclitaxel; Paclitaxel (80mg/m^2) will be administered IV on days 1 and 8 starting with Cycle 2. Each Cycle is 21 days.; Other Names: Taxol; Drug: Olaparib; Olaparib (100mg or 300mg) will be administered orally on Days 1-21 of each Cycle. Each Cycle is 21 days.; Other Names: Lynparza; Drug: Pembrolizumab; Pembrolizumab (200mg) will be administered IV on day 1 of each Cycle. Each Cycle is 21 days.; Other Names: MK-3475; Keytruda
Experimental: Arm 2: Unmeasurable Disease	Drug: Paclitaxel; Paclitaxel (80mg/m^2) will be administered IV on days 1 and 8 starting with Cycle 2. Each Cycle is 21 days.; Other Names: Taxol; Drug: Olaparib; Olaparib (100mg or 300mg) will be administered orally on Days 1-21 of each Cycle. Each Cycle is 21 days.; Other Names: Lynparza; Drug: Pembrolizumab; Pembrolizumab (200mg) will be administered IV on day 1 of each Cycle. Each Cycle is 21 days.; Other Names: MK-3475; Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival is the time from the start of first dose of study drug to death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	Up to 27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Events (AEs)	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject. Laboratory abnormalities that were asymptomatic and not clinically significant were excluded.	15 months
Number of Participants Experiencing Immune-related Adverse Events (irAEs)	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject. Laboratory abnormalities that were asymptomatic and not clinically significant were excluded.	15 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Katherine Bever, MD, Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2020
• Primary Completion (Actual): November 17, 2025
• Study Completion (Actual): November 17, 2025

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: December 20, 2019
• First Posted (Actual): December 24, 2019

Study Record Updates

• Last Update Posted (Actual): September 1, 2026
• Last Update Submitted That Met QC Criteria: August 10, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Gastric Cancer; Anti-PD-1; Pembrolizumab; Olaparib; Paclitaxel; PARP inhibitors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Paclitaxel; pembrolizumab; olaparib
• Other Study ID Numbers: J19135; IRB00209006 (Other Identifier: Johns Hopkins Medical Institution)

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