Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

OS is defined as time from date of randomization to date of death due to any cause. Patients who did not die on study are censored at the date of the last on-study follow-up that the patient was known to be alive (including follow-up data). Results obtained via Kaplan-Meier estimation, Brookmeyer and Crowley (1982) method.

Time frame: From randomization date to date of death due to any cause (Up to approximately 44 months)

Population: Intent-to-Treat population: all randomized participants.

1-Year Survival will be defined as the percentage of participants surviving at 1 year after the first dose. Results obtained via Kaplan-Meier estimation, Greenwood's formula (1980).

Time frame: At 12 months from first dose

Population: Intent-to-Treat Population: All randomized participants

The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index (HUI) is assessed using the Crosswalk algorithm for France based on the individual responses to the 5 EQ-5D-5L domains ranging from -0.530 to 1.000. The smallest change considered clinically meaningful, is defined as a score difference of 0.08 points.

Time frame: Clinic visit closest to the disease evaluation on weeks 9, 17, 25, 33, 41, 49.

Population: Intent-to-Treat population (all randomized participants) with available scores for each assessment.

The Visual Analogue Score (VAS) is a component of the EQ-5D-5L and assesses the patient's self-rated health using a vertical visual analogue scale where numbered 0 (the worst health you can image) to 100 (the best health you can imageine). The smallest change considered clinically meaningful, is defined as a score difference of 7 points.

Time frame: Clinic visit closest to the disease evaluation on weeks 9, 17, 25, 33, 41, 49.

Population: Intent-to-Treat population (all randomized participants) with available scores for each assessment.

The LCSS is a lung cancer specific measure of quality of life and includes 9 questions, including patient-reported ratings of six symptoms (appetite loss, fatigue, cough, dyspnea, hemoptysis, pain) and three summary items (symptom distress, activity level, overall quality of life) using 100-mm visual analogue scales ranging from 0 (lowest rating) to 100 (highest rating). The average total score = is a sum of items 1 to 9 divided by the total number of items (sum of items 1 to 9) / 9).

Time frame: Clinic visit closest to the disease evaluation on weeks 9, 17, 25, 33, 41, 49.

Population: Intent-to-Treat population (all randomized participants) with available scores for each assessment.

CBR is defined as the percentage of patients documented to have a confirmed CR, confirmed PR, or SD, according to RECIST 1.1 as the best response. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.

Time frame: From randomization until disease progression or start of new anti-cancer therapy (Up to approximately 44 months)

Population: The Modified Intent-to-Treat Population: all patients who are randomized into this study and have measurable disease (per RECIST 1.1) at baseline.

DOR is defined as the time from date of the first documentation of confirmed objective response (CR or PR) to the first documentation of disease progression (PD) or to death due to any cause in the absence of documented PD. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progressive Disease (PD) is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions. Results obtained via Kaplan-Meier estimation, Brookmeyer and Crowley (1982) method.

Time frame: From randomization to the first documentation of disease progression (PD) or to death due to any cause in the absence of documented PD (Up to approximately 44 months)

Population: Modified Intent-to-Treat Population (all patients who are randomized into this study and have measurable disease (per RECIST 1.1) at baseline) with a confirmed objective response (CR or PR) per central radiographic assessment.

The severity of chemistry results were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0); Chemistry parameters were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death. Number of participants with maximum post baseline grades is presented. Grade 0 is defined as absence of an AE or within normal limits. Baseline is defined as the last pre-dose assessment.

Time frame: From first dose up to 28 days post last dose (Up to an average of 7.5 months and maximum of 36 months)

Population: Safety Population (all patients who received any dose of study medication) with at least 1 post-baseline result

The severity of hematology results were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0); Hematology parameters were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death. Number of participants with maximum post baseline grades is presented. Grade 0 is defined as absence of an AE or within normal limits. Baseline is defined as the last pre-dose assessment.

Time frame: From first dose up to 28 days post last dose (Up to an average of 7.5 months and maximum of 36 months)

Population: Safety Population (all patients who received any dose of study medication) with at least 1 post-baseline result

An adverse event (AE) is any reaction, side effect or other undesirable medical event that occurs during participation in a clinical trial, regardless of treatment group or suspected causal relationship to study treatment. A treatment emergent AE (TEAE) is an AE that occurs after the first dose of any study treatment or any preexisting condition that increases in severity after the first dose of study treatment.

Time frame: From first dose up to 28 days post last dose, and up to 100 days post last dose of nivolumab for immune-related AEs (Up to maximum of 38 months)

Population: Safety Population: all patients who received any dose of study medication (i.e., sitravatinib, nivolumab or docetaxel)

An adverse event (AE) is any reaction, side effect or other undesirable medical event that occurs during participation in a clinical trial, regardless of treatment group or suspected causal relationship to study treatment. Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. A treatment emergent AE (TEAE) is an AE that occurs after the first dose of any study treatment or any preexisting condition that increases in severity after the first dose of study treatment. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Death).

Time frame: From first dose up to 28 days post last dose, and up to 100 days post last dose of nivolumab for immune-related AEs (Up to maximum of 38 months)

Population: Safety Population: all patients who received any dose of study medication (i.e., sitravatinib, nivolumab or docetaxel)

ORR is defined as percentage of participants with confirmed 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. Patients who cannot be assessed for response are counted as non-responders. CR is defined as complete disappearance of all target lesions with the exception of nodal disease; PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions.

Time frame: From randomization until disease progression or start of new anti-cancer therapy (Up to approximately 44 months)

Population: The Modified Intent-to-Treat Population: all patients who are randomized into this study and have measurable disease (per RECIST 1.1) at baseline per central radiographic assessment.

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. Progressive Disease (PD) is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions. Censoring was assigned on the date of the last tumor assessment if no assessment of tumor progression is identified and the patient does not die while on study. Patients with no evaluation of disease after first study treatment will have PFS censored on the date of randomization. Patients who start new anti-cancer therapy prior to documented PD will be censored at the date of the last tumor assessment prior to the start of the new therapy. Results obtained using Kaplan-Meier estimation, Brookmeyer and Crowley (1982) method.

Time frame: From randomization to the date of the first documentation of objective disease progression or death due to any cause (Up to approximately 44 months)

Population: Intent-to-Treat population: all randomized participants.

Time frame: 0.5 hours post dose on cycle 1 (day 1) and 5 hours post dose on cycle 1 (day 1 and 15), and pre-dose on cycle 1 (day 15), and cycle 2, 3, and 5 (day 1)

Population: Pharmacokinetic Evaluable Population - all patients who received treatment with sitravatinib and had sufficient concentration-time data to permit calculation for sitravatinib at each time point