A Randomized Phase 3 Study of Sitravatinib in Combination with Nivolumab Versus Docetaxel in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer with Disease Progression On or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy (SAPPHIRE)
- Conditions
- Non-Squamous Non-Small Cell Lung Cancer10038666
- Registration Number
- NL-OMON54407
- Lead Sponsor
- Mirati Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 75
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study. 1. Histologically or cytologically confirmed non-squamous NSCLC with metastatic (Stage IV) or unresectable, locally advanced (Stage IIIB/IIIC) disease, not amenable to treatment with curative intent including concurrent chemoradiotherapy. 2. Receipt of at least one but not more than two prior treatment regimens in the advanced disease setting to include: * Treatment with a CIT (i.e., anti-PD-1/PD-L1) and a platinum-based chemotherapy, which may have been in combination or in sequence (i.e., platinum-based chemotherapy followed by CIT) o Prior treatment may have included maintenance therapy with a chemotherapy agent (e.g., pemetrexed) and/or a CIT * Most recent treatment regimen must have included a CIT with radiographic disease progression on or after treatment, for example: o 1 prior treatment regimen: platinum-based chemotherapy in combination with CIT radiographic disease progression, or o 2 prior treatment regimens: platinum-based chemotherapy -> disease progression * CIT -> radiographic disease progression* NOTE: Platinum-based adjuvant, neoadjuvant, or definitive chemoradiation therapy given for locally advanced disease followed by recurrent or metastatic disease within 6 months of completing chemotherapy may be considered treatment in the advanced disease setting. 3. Duration of at least 4 months (120 days) from first dose of most recent CIT to date of radiographic disease progression. 4. Availability of source documents for historical disease evaluations to allow Investigator certification of disease progression on or after most recent CIT. 5. Most recent prior therapy (e.g., chemotherapy, CIT, or radiation therapy) discontinued at minimum of 2 weeks before the date of randomization; palliative radiation therapy to skeletal metastases and stereotactic radiation for brain metastases allowed if discontinued at least 7 days before the date of randomization. 6. Candidacy to receive treatment with docetaxel as the next line of therapy if randomized to the comparator arm. 7. Recovery from adverse effects of prior therapy to baseline or Grade 1 (excluding alopecia). 8. >= 18 years of age. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 10. Life expectancy of at least 3 months. 11. Adequate bone marrow and organ function demonstrated by: a. Absolute neutrophil count **1,500/mm3 (**1.5 × 109/L). b. Hemoglobin >= 9.0 g/dL not dependent on transfusion support. c. Platelet count >= 100 × 109/L (>= 100,000 per mm3). d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 1.5 × ULN with alkaline phosphatase <= 2.5 × ULN. e. Serum bilirubin <= 1.0 x ULN. f. Calculated creatinine clearance >= 40 mL/min, using the Cockcroft-Gault formula. 12. Women of child-bearing potential (WOCBP) or men whose partner is a WOCBP agrees to use contraception while participating in this study, and for a period of 6 months following termination of study treatment. 13. Completed informed consent process, including signing IRB/EC-approved informed consent form. 14. Willing to comply with clinical trial instructions and requirements.
Patients presenting with any of the following will not be included in the study: 1. Discontinuation of prior treatment with CIT more than 90 days prior to the date of randomization. 2. Receipt of systemic cancer therapy since discontinuation of CIT, with the exception of maintenance chemotherapy. 3. Active brain metastases. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable (except for residual signs or symptoms related to the central nervous system (CNS) treatment) for at least 2 weeks prior to randomization without the use of anticonvulsants and without the use of corticosteroids (or are on a stable or decreasing dose of <=10 mg daily prednisone or equivalent). 4. Carcinomatous meningitis. 5. Known history of tumors that test positive for EGFR, ROS1, ALK mutations, or ALK fusions. 6. Prior therapies: a. Immunotherapies not previously specified, including anti-OX40 and anti-CD137; prior anti-CTLA-4 is permitted. b. Cancer therapy having the same mechanism of action as sitravatinib (e.g., tyrosine kinase inhibitor with a similar target profile or bevacizumab). 7. Known toxicity on prior checkpoint inhibitor treatment: a. >= Grade 3 immune-related AE related to checkpoint inhibitor. b. Grade 2 immune-related AE associated with checkpoint inhibitor unless the AE resolved or was well controlled by withholding the checkpoint inhibitor and/or treatment with steroids, with the exception of prior colitis, myocarditis, and pneumonitis, which are exclusionary. c. CNS or ocular AE of any grade related to checkpoint inhibitor. NOTE: Patients with a prior endocrine AE are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic. 8. Active or prior documented autoimmune disease: a. Inflammatory bowel disease (e.g., Crohn*s disease, ulcerative colitis). b. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. c. Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with Type 1 diabetes, vitiligo, Graves* disease, residual hypothyroidism due to an autoimmune condition only requiring hormone replacement, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. 9. Active or prior immunocompromising conditions: a. Current or prior use of immunosuppressive medication within 28 days before the date of randomization, with the exceptions of topical, ocular, intranasal and inhaled corticosteroids (with minimal systemic absorption) or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. A brief course (<= 3 days) of systemic corticosteroids >10 mg/day of prednisone (or equivalent corticosteroid) for prophylaxis (e.g., contrast dye allergy) or for treatment of non-immune conditions (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is permitted within the 28 days. b. Known acute or chronic human immunodeficiency virus (HIV); i. Sites in Germany and Switzerland only: HIV infection at screening (positive HIV test). c. History of primary immunodeficiency. d. History of allogeneic transplant. 10. History of severe hypersensitivity reaction to any monoclonal antibody or polysorbate 80. 11. Criterion #11 removed, but numbering maintained 12. Use of live vaccines against infectious disease (e.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall Survival (OS)</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Safety characterized by type, incidence, severity, timing, seriousness and<br /><br>relationship to study treatment of adverse events, laboratory abnormalities,<br /><br>and number of patients discontinuing study treatment due to an adverse event.<br /><br><br /><br>• Secondary efficacy endpoints:<br /><br>* - Objective Response Rate (ORR) as defined by Response Evaluation Criteria in<br /><br>Solid Tumors version 1.1 (RECIST 1.1).<br /><br>* - Duration of Response (DOR);<br /><br>* - Clinical Benefit Rate (CBR);<br /><br>* - Progression-Free Survival (PFS); and<br /><br>* - 1-Year Survival Rate.<br /><br>• Blood plasma concentrations of MGCD516.<br /><br>• Patient reported outcome (PROs):<br /><br>* - Lung Cancer Symptom Scale (LCSS); and<br /><br>* - European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L).</p><br>