Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM)

NCT03175172 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ADU-CL-13KEYNOTE KN-701
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to evaluate whether CRS-207 with pembrolizumab is safe and effective in adults with MPM who have failed prior anti-cancer therapy.

Conditions

Malignant Pleural Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  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 assessed subject as measured by modified response evaluation criteria in solid tumors (modified RECIST) for MPM (Byrne and Nowak, 2004) 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.

  BOR was assessed from the 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.

Secondary Outcomes (4)

• Disease Control Rate (DCR)

  BOR was assessed from the 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.

• Progression-Free Survival (PFS)

  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 9 weeks.

• Improvement in Pulmonary Function

  Subjects tested by spirometry at Screening and up to 7 days prior to dosing every other cycle starting at Cycle 3 until 4 weeks post final dose, assessed up to 16 weeks.

• Overall Survival (OS)

  OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 25 weeks.

Study Arms (1)

Experimental

EXPERIMENTAL

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; Biological: Pembrolizumab

Interventions

CRS-207 BIOLOGICAL

Administered by IV infusion over approximately 1 hour.

Experimental

Pembrolizumab BIOLOGICAL

Administered by IV infusion over approximately 30 minutes.

Also known as: MK-3475

Experimental

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a predominantly (≥50%) epithelial component
• No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate organ and marrow function
• Adequate lung function; forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) ≥ 45% of predicted value as measured by spirometry; and oxygen saturation ≥ 90% on room air

You may not qualify if:

• Pleurodesis within 14 days prior to first dose of study drug
• 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
• Active secondary malignancy
• Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug, or not recovered from adverse effects due to agents administered more than 4 weeks earlier
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other checkpoint pathways (e.g. CTLA-4)
• Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer vaccine, or adoptive T cell immunotherapy
• 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.

Sponsors & Collaborators

• Aduro Biotech, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

UCSF Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

NIH National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Laura & Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol. 2004 Feb;15(2):257-60. doi: 10.1093/annonc/mdh059.

  PMID: 14760119 BACKGROUND

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Study was terminated early and included a small number of subjects, and insufficient data were available to evaluate the clinical activity of the study treatment. Due to low enrollment, some protocol-specified outcome measures were not evaluated.

Results Point of Contact

• Title: Medical Affairs
• Organization: Aduro Biotech, Inc.

MedicalAffairs@aduro.com

510.809.2452

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 5, 2017
• Study Start: May 31, 2017
• Primary Completion: January 9, 2018
• Study Completion: January 31, 2018
• Last Updated: April 4, 2019
• Results First Posted: February 19, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)