Safety and Efficacy of CRS-207 With Pembrolizumab in Gastric, Gastroesophageal Junction or Esophageal Cancers

• ClinicalTrials.gov Identifier: NCT03122548
• Recruitment Status: Terminated
• First Posted: April 21, 2017
• Results First Posted: February 20, 2019
• Last Update Posted: April 4, 2019
• Sponsor: Aduro Biotech, Inc.
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Aduro Biotech, Inc.

Study Description

Brief Summary:

The purpose of this study is to determine whether CRS-207 in combination with pembrolizumab is safe and effective in adults with recurrent or metastatic gastric, gastroesophageal junction, or esophageal cancer who have received one or two prior chemotherapy regimens for advanced disease.

Condition or disease	Intervention/treatment	Phase
Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Esophageal Adenocarcinoma	Biological: CRS-207; Biological: Pembrolizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label Evaluation of CRS-207 and Pembrolizumab in Adults With Recurrent or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinomas
• Actual Study Start Date: August 14, 2017
• Actual Primary Completion Date: December 27, 2017
• Actual Study Completion Date: January 31, 2018

Arms and Interventions

Arm

Intervention/treatment

Experimental: CRS-207 + Pembrolizumab; CRS-207 and pembrolizumab will be administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) will be administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony-forming units [CFU]) will be administered by IV infusion over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will continue to be administered on Day 1 at each treatment cycle (every 3 weeks); CRS-207 will be administered once every 6 weeks (every other cycle). Treatment will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit.

Biological: CRS-207; Administered by IV infusion over 1 hour.; Biological: Pembrolizumab; Administered by IV infusion over 30 minutes.; Other Name: MK-3475

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. ]
   ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each evaluable subject as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure. .

Secondary Outcome Measures :

1. Disease Control Rate (DCR) [ Time Frame: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. ]
   The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per RECIST v1.1.
2. Progression-Free Survival (PFS) [ Time Frame: Subjects followed for disease progression from first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. ]
   Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) according to RECIST v1.1 or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects who do not experience PD and are alive on or before the data cut-off date will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
3. Duration of Response (DOR) [ Time Frame: DOR assessed from the date of a post-baseline tumor assessment of CR or PR per RECIST v1.1 until the date of documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. ]
   Number of weeks from the first date a study subject achieved an objective disease response of CR or PR according to RECIST v1.1 to the date a study subject exhibited PD or death due to any cause, estimated using KM methods with 95% CIs. Subjects who do not experience PD or death at the time of analysis will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
4. Overall Survival (OS) [ Time Frame: OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 15 weeks. ]
   Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive, or the data cut-off date, whichever is earlier.

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:

1. Diagnosis with confirmed histology of one or more of the following:

   • Histologically-confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma (Siewert type II/III classification), or
   • Histologically-confirmed inoperable superior, medial, or distal third esophageal adenocarcinoma (Siewert type I classification may be included, provided there is no mixed histology)
2. Confirmed recurrent or metastatic disease
3. Received and experienced disease progression on, or following one or two prior chemotherapy regimens for advanced disease.
4. HER-2/neu negative or, if HER-2/neu positive, disease must have previously progressed on treatment with trastuzumab; prior treatment must have included a platinum and a fluoropyrimidine.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Can provide tissue for PD-L1 and mesothelin biomarker analysis
7. Adequate organ and marrow function at screening

Exclusion Criteria:

1. Diagnosis of squamous or undifferentiated gastric cancer
2. Individuals with inaccessible tumors or for whom biopsy is contraindicated
3. Participated in any other study in which receipt of an investigational new drug or investigational device occurred within 28 days of first dose of study drug
4. Receiving tumor necrosis factor (TNF) pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
5. Clinical evidence of ascites by physical exam
6. Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug or has not recovered from adverse effects due to agents administered more than 4 weeks earlier
7. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug, or has not recovered from adverse effects due to a previously-administered agent
8. Subjects who have implanted medical devices that pose high risks for colonization and cannot be easily removed (e.g. artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), metal plate(s)) if infection occurs. Other common devices such as venous access devices (e.g. Port-a-Cath or Mediport) may be permitted as well as arterial and venous stents and dental and breast implants that were placed more than 3 months prior to first dose of study drug.

Contacts and Locations

Locations

United States, California

UCLA Medical Center

Los Angeles, California, United States, 90095

United States, Colorado

University of Colorado

Aurora, Colorado, United States, 80045

United States, Illinois

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, Texas

Mary Crowley Cancer Research

Dallas, Texas, United States, 75230

United States, Washington

Virginia Mason Medical Center

Seattle, Washington, United States, 98101

Sponsors and Collaborators

Aduro Biotech, Inc.

Merck Sharp & Dohme Corp.

  Study Documents (Full-Text)

Documents provided by Aduro Biotech, Inc.:

Study Protocol  [PDF] August 22, 2017

Statistical Analysis Plan  [PDF] March 13, 2018

More Information

• Responsible Party: Aduro Biotech, Inc.
• ClinicalTrials.gov Identifier: NCT03122548
• Other Study ID Numbers: ADU-CL-14; KEYNOTE KN-463 ( Other Identifier: Merck Sharp & Dohme Corp. )
• First Posted: April 21, 2017
• Results First Posted: February 20, 2019
• Last Update Posted: April 4, 2019
• Last Verified: March 2019

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 Aduro Biotech, Inc.:

stomach cancer; gastric cancer; esophageal cancer; digestive system diseases; gastrointestinal diseases; stomach diseases

Additional relevant MeSH terms:

Adenocarcinoma; Esophageal Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents