This study will compare the efficacy of the investigational agent sitravatinib in combination with nivolumab versus docetaxel in patients with advanced non-squamous NSCLC who have previously experienced disease progression on or after platinum-based chemotherapy and checkpoint inhibitor therapy.
Recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| Nivolumab | Opdivo | Nivolumab and Sitravatinib |
| Sitravatinib | MGCD516 | Nivolumab and Sitravatinib |
| Docetaxel | Taxotere | Docetaxel |
Sitravatinib (MGCD516) is an orally-available, small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, TAM (Tyro3, AXL, MERTK) family, VEGFR family, PDGFR family, KIT, FLT3, TRK family, RET, DDR2, and selected EPH family members. Nivolumab is a human IgG monoclonal antibody that binds to the PD-1 receptor and selectively blocks the interaction with its ligands PD-L1 and PD-L2, thereby releasing PD-1 pathway mediated inhibition of the immune response, including anti-tumor immune response. RTKs have been implicated in mediating an immunosuppressive tumor microenvironment, which has emerged as a potential resistance mechanism to checkpoint inhibitor therapy. Inhibition of these RTKs by sitravatinib may augment anti-tumor immune response and improve outcomes by overcoming resistance to checkpoint inhibitor therapy.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Nivolumab and Sitravatinib | Experimental | Nivolumab will be administered by intravenous infusion over 30 minutes at 240 mg every 2 weeks or at 480 mg every 4 weeks. Sitravatinib capsules will be administered orally, once daily. |
|
| Docetaxel | Active Comparator | Docetaxel will be administered by intravenous infusion at 75 mg/m2 over 1 hour every 3 weeks. |
|
Inclusion Criteria:
- Diagnosis of Non-Squamous Non-Small Cell Lung Cancer
- Receipt of at least one but not more than two prior treatment regimens in the advanced
setting
- Prior treatment with PD-1/PD-L1 checkpoint inhibitor therapy and platinum-based
chemotherapy in combination or in sequence (i.e., platinum-based chemotheraphy
followed by checkpoint inhibitor therapy)
- Most recent treatment regimen must have included a checkpoint inhibitor therapy with
radiographic disease progression on or after treatment
- Candidate to receive docetaxel as second or third line therapy
Exclusion Criteria:
- Uncontrolled brain metastases
- Tumors that have tested positive for EGFR, ROS1, ALK mutations, or ALK fusions
- Unacceptable toxicity with prior checkpoint inhibitor therapy
- Receipt of systemic anti-cancer therapy post checkpoint inhibitor therapy, other than
maintenance chemotherapy
- Impaired heart function
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Overall Survival (OS) |
| Time Frame: | 36 Months |
| Safety Issue: | |
| Description: | OS is defined as time from date of randomization to date of death due to any cause |
| Measure: | Adverse Events (AEs) |
| Time Frame: | 36 Months |
| Safety Issue: | |
| Description: | Frequency of patients experiencing treatment-emergent AEs |
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | 36 Months |
| Safety Issue: | |
| Description: | ORR defined as complete response (CR) or partial response (PR) per RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy |
| Measure: | Progression-Free Survival (PFS) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | PFS is defined as the time from randomization to the date of the first documentation of objective disease progression or death due to any cause |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Mirati Therapeutics Inc. |
August 30, 2021
