Primary Outcome Measures
- Objective Response Rate [ Time Frame: Through study completion, an average of 18 months ]
Defined as the proportion of subjects with complete response (CR) or partial response (PR); Modified RECIST (Response Evaluation Criteria in Solid Tumors) for MPM (Byrne and Nowak, 2004) will be used to assess tumor response and progression.
Secondary Outcome Measures
- Disease Control Rate [ Time Frame: Through study completion, an average of 18 months ]
Defined as the percentage of subjects with CR, PR, or stable disease (SD) - rogression Free Survival [ Time Frame: Through study completion, an average of 18 months ]
Defined as time from first dose of study drug until disease progression or death - Improvement in pulmonary function (FVC) [ Time Frame: Through study completion, an average of 18 months ].Proportion of subjects with improvement in pulmonary function (FVC), defined as an increase from baseline of either ≥400 mL or ≥20% assessed using spirometry.
- Overall Survival (OS) [ Time Frame: Through study completion, an average of 18 months ]
As measured from date of first dose of study drug until death
Detailed 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.
Eligibility
- Inclusion Criteria
- 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.
- Measurable disease as defined by modified RECIST for MPM (Byrne and Nowak, 2004)
- 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
- Exclusion Criteria
- Pleurodesis within 14 days prior to first dose of study drug
- Receiving 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.
