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

Malignant Pleural Mesothelioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03175172
• Other study ID #: ADU-CL-13
• Secondary ID: KEYNOTE KN-701
• Status: Terminated
• Phase: Phase 2
• Start date: May 31, 2017
• Est. completion date: January 31, 2018

Study information

• Verified date: March 2019
• Source: Aduro Biotech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: January 31, 2018
• Est. primary completion date: January 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a predominantly (=50%) epithelial component

2. No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

4. Adequate organ and marrow function

5. 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

Exclusion Criteria

1. Pleurodesis within 14 days prior to first dose of study drug

2. 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

3. Active secondary malignancy

4. 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

5. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug

6. History of (non-infectious) pneumonitis that required steroids or current pneumonitis

7. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other checkpoint pathways (e.g. CTLA-4)

8. Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer vaccine, or adoptive T cell immunotherapy

9. 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.

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma
• Mesothelioma

Intervention

Biological:
• CRS-207
Administered by IV infusion over approximately 1 hour.
• Pembrolizumab
Administered by IV infusion over approximately 30 minutes.

Locations

Country	Name	City	State
United States	NIH National Cancer Institute	Bethesda	Maryland
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Aduro Biotech, Inc.	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease Control Rate (DCR)	The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per modified RECIST for MPM.	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	Progression-Free Survival (PFS)	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.	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.
Secondary	Improvement in Pulmonary Function	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	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.
Secondary	Overall Survival (OS)	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.	OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 25 weeks.