Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Administered by IV infusion over approximately 1 hour.

CRS-207

Administered by IV infusion over approximately 30 minutes.

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.

The population for this study will consist of approximately 35 adults with histologically-confirmed MPM (epithelial or biphasic) whose disease has progressed after 1-2 prior anti-cancer therapies.

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

A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 With Pembrolizumab in Adults With Previously-Treated Malignant Pleural Mesothelioma

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.

The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per modified RECIST for MPM.

Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) (per modified RECIST for MPM) or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CI). 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 tumor assessment or data cut-off date, whichever is earlier.

Percentage of subjects with improvement in forced vital capacity (FVC), defined as an increase from baseline of either ≥400 mL or ≥20% assessed using spirometry

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.

Merck Sharp & Dohme LLC

Aduro Biotech, Inc.

AEs reported for the SAF. Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.

CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by IV infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 CFU) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).

Experimental

Age, Categorical

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Not Reported

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Baseline analysis provided for all subjects who were administered at least 1 dose of protocol-specified drug (the Safety Analysis Set \[SAF\]).

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.

Medical Affairs

Analysis based on subjects who received ≥1 dose of study treatment and had ≥1 evaluable post-baseline modified RECIST for MPM tumor response assessment or were discontinued due to toxicity (the Evaluable Analysis Set \[EAS\]). 1 subject did not have post-baseline tumor response assessments and could not be evaluated for this outcome measure.

Overall Response Rate (ORR)

Disease Control Rate (DCR)

Analysis of PFS was performed on subjects in the SAF.

Progression-Free Survival (PFS)

Analysis of FVC was performed on all subjects in the SAF. No subjects showed improvement in FVC.

Improvement in Pulmonary Function

Analysis of OS was performed on subjects in the SAF.

Overall Survival (OS)

CRS-207 and pembrolizumab were administered in 3-week cycles. For Cycle 1, pembrolizumab (200 mg) was administered by intravenous (IV) infusion over 30 minutes on Day 1 and CRS-207 (starting dose 1 × 10e9 colony forming units \[CFU\]) was administered by IV infusion over 1 hour on Day 2. If tolerated, pembrolizumab and CRS-207 were administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab continued to be administered on Day 1 at each treatment cycle (every 3 weeks); and CRS-207 was administered once every 6 weeks (every other cycle).

Spots Global Cancer Trial Database for Evaluation of CRS-207 With Pembrolizumab in Previously Treated Malignant Pleural Mesothelioma (MPM)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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