Advanced and/or Metastatic Solid Tumors, Advanced/Metastatic Unresectable Malignant Pleural Mesothelioma, Stage IIIB Not Amenable to Curative Therapy to Stage IV Non-small Cell Lung Cancer
Conditions
Keywords
solid tumors, non-small cell lung cancer, malignant pleural mesothelioma, chemotherapy, programmed cell death protein 1 (PD-1) inhibitor
Brief summary
The purpose of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose of INCMGA00012 in combination with common standard-of-care chemotherapy regimens in participants with advanced solid tumors.
Interventions
DRUGRetifanlimab
INCMGA00012 administered intravenously every 3 weeks.
DRUGGemcitabine
Gemcitabine administered intravenously on Days 1 and 8 of 21-day cycles.
DRUGCisplatin
Cisplatin administered intravenously on Day 1 of 21-day cycles.
DRUGPemetrexed
Pemetrexed administered intravenously on Day 1 of 21-day cycles.
DRUGCarboplatin
Carboplatin AUC5 or AUC6 administered intravenously on Day 1 of 21-day cycles.
DRUGPaclitaxel
Paclitaxel administered intravenously on Day 1 of 21-day cycles.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced and/or metastatic solid tumors including the following: histologically or cytologically confirmed diagnosis of Stage IIIB not amenable to curative treatment or Stage IV non-small cell lung cancer (pemetrexed-platinum treatment groups must have nonsquamous histology type); and histologically or cytologically confirmed diagnosis of advanced/metastatic unresectable malignant pleural mesothelioma. * No prior systemic treatment with the following exceptions: participants with a known sensitizing mutation (eg, BRAF, EGFR, ALK, or ROS1) should have had disease progression on or following an approved targeted tyrosine kinase inhibitor; and participants who received adjuvant or neoadjuvant chemotherapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months before the date of enrollment. * Measurable or nonmeasurable tumor lesions per RECIST v1.1. * Eastern Cooperative Oncology Group performance status 0 to 1.
Exclusion criteria
* Received prior treatment with checkpoint inhibitor agents (such as anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4). * Had major surgery within 3 weeks before the first dose of study treatment. * Received radiation therapy to the lung(s) that is \> 30 Gy within 6 months of the first dose of study treatment. * Received palliative radiotherapy within 7 days before the first dose of study treatment. * Has ≥ Grade 2 residual toxicities from the most recent prior therapy (except alopecia). * Organ function (renal, hepatic), bone marrow reserve, and coagulation panel outside the protocol-defined laboratory values. * Is currently participating and receiving investigational therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks before the first dose of study treatment. * Has active autoimmune disease requiring systemic immunosuppression with corticosteroids (\> 10 mg once daily of prednisone or equivalent) or immunosuppressive drugs within 2 years before the first dose of study treatment. * Is on chronic systemic steroids (\> 10 mg once daily of prednisone or equivalent). * Known active central nervous system metastases and/or carcinomatous meningitis (patients with previously-treated and clinically stable brain metastases are eligible and a washout period of ≥ 4 weeks since radiation therapy is required). * Known additional malignancy that is progressing or requires active treatment. * Evidence of interstitial lung disease or active, noninfectious pneumonitis. * History of organ transplant, including allogeneic stem cell transplantation. * Active infections requiring systemic antibiotics. * Known active hepatitis B or C. * Has a diagnosis of immunodeficiency, including participants known to be HIV positive (positive for HIV 1/2 antibodies). * Significant cardiac event within 6 months before Cycle 1 Day 1. * Has received a live vaccine within 28 days of the planned start of study treatment. * Known hypersensitivity to any component of the study drugs, excipients, or another monoclonal antibody which cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment-emergent adverse events with INCMGA00012 in combination with chemotherapy | Up to approximately 27 months | Adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) | Through study completion, up to approximately 31 months | Defined as the time from an initial objective response (CR or PR) according to RECIST v1.1 until disease progression as determined by investigator assessment or death due to any cause. |
| Disease control rate (DCR) | Through study completion, up to approximately 31 months | Defined as the number of participants with CR or PR as best response or stable disease that was maintained for at least 12 weeks. |
| Cmax of INCMGA00012 when given in combination with chemotherapy agents | Through post-induction Cycle 5 Day 1, up to 15 weeks | Maximum observed plasma or serum concentration. |
| Objective response rate (ORR) | Through study completion, up to approximately 31 months | Defined as the percentage of participants having complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by investigator assessment. |
| Cmin of INCMGA00012 when given in combination with chemotherapy agents | Through post-induction Cycle 5 Day 1, up to 15 weeks | Minimum observed plasma or serum concentration over the dose interval. |
| AUC0-t of INCMGA00012 when given in combination with chemotherapy agents | Through post-induction Cycle 5 Day 1, up to 15 weeks | Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t. |
| Tmax of INCMGA00012 when given in combination with chemotherapy agents | Through post-induction Cycle 5 Day 1, up to 15 weeks | Time to maximum concentration. |
Outcome results
None listed