Sitravatinib Plus Pembrolizumab in Patients With Advanced Treatment-Naïve PD-L1+ Non-Squamous NSCLC

NCT04925986 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2000030093
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicohort phase 2 study to evaluate the efficacy of pembrolizumab combined with the investigational drug sitravatinib in the frontline treatment of advanced, non-squamous PD-L1 positive NSCLC.

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Diseases; Lung Neoplasms; Metastatic Lung Non-Small Cell Carcinoma; Stage IV Lung Non-Small Cell Cancer AJCC v7; PD-L1 Gene Mutation; Advanced Treatment-Naïve PD-L1; Sitravatinib; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The Objective Response Rate (ORR): The primary endpoint for this study will be ORR as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in the main study population. Presented are counts of participants in the following RECIST categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD)

  up to 267 days

Secondary Outcomes (5)

• Overall Survival (OS)

  until death or date of last contact, up to 2 years

• Progression Free Survival (PFS)

  Until progressive disease, death, or last contact, up to 2 years

• Duration of Response (DOR)

  Until progressive disease, death, or last contact, up to 2 years

• Clinical Benefit Rate (CBR)

  up to 2 years

• Number of Participants That Experienced at Least 1 Adverse Event

  2 years

Study Arms (4)

Group 1A: PD-L1 1-49%, Main Study Population

EXPERIMENTAL

Participants with PD-L1 Tumor Proportion Score (TPS) 1-49% receive Pembrolizumab 200mg intravenous (IV) every 3 weeks (Q3w) and Sitravatinib 100mg PO (by mouth) daily, beginning on cycle 1 day 1 (C1D1).

Drug: Sitravatinib; Drug: Pembrolizumab

Group 1B: PD-L1 1-49%, Pembrolizumab run-in population

EXPERIMENTAL

Participants with PD-L1 Tumor Proportion Score (TPS) 1-49% receive Pembrolizumab 200mg intravenous (IV) for one dose alone, beginning on cycle 1 day 1 (C1D1). On Cycle 2 Day 1 (C2D1), participants receive Pembrolizumab 200mg intravenous (IV) once every 3 weeks (Q3w) and Sitravatinib 100mg PO (by mouth) daily.

Drug: Sitravatinib; Drug: Pembrolizumab

Group 2A: PD-L1 ≥ 50%, Main Study Population

EXPERIMENTAL

Participants with PD-L1 Tumor Proportion Score (TPS) ≥ 50% receive Pembrolizumab 200mg intravenous (IV) every 3 weeks (Q3w) and Sitravatinib 100mg PO (by mouth) daily, beginning on cycle 1 day 1 (C1D1).

Drug: Sitravatinib; Drug: Pembrolizumab

Group 2B: PD-L1 ≥ 50%, Pembrolizumab run-in population

EXPERIMENTAL

Participants with PD-L1 Tumor Proportion Score (TPS) ≥ 50% receive Pembrolizumab 200mg intravenous (IV) for one dose alone, beginning on cycle 1 day 1 (C1D1). On Cycle 2 Day 1 (C2D1), participants receive Pembrolizumab 200mg intravenous (IV) once every 3 weeks (Q3w) and Sitravatinib 100mg PO (by mouth) daily.

Drug: Sitravatinib; Drug: Pembrolizumab

Interventions

Sitravatinib DRUG

Groups 1A and 2A receive Sitravatinib 100mg orally (PO) daily starting on cycle 1 day 1 (C1D1). Groups 1B and 2B) receive Sitravatinib 100mg orally (PO) daily starting on Cycle 2 Day 1 (C2D1).

Also known as: IND 155305

Group 1A: PD-L1 1-49%, Main Study Population; Group 1B: PD-L1 1-49%, Pembrolizumab run-in population; Group 2A: PD-L1 ≥ 50%, Main Study Population; Group 2B: PD-L1 ≥ 50%, Pembrolizumab run-in population

Pembrolizumab DRUG

All groups (1A, 1B, 2A, 2B) receive Pembrolizumab 200mg intravenous every three weeks (IV Q3w) on cycle 1 day 1 (C1D1).

Also known as: Keytruda

Group 1A: PD-L1 1-49%, Main Study Population; Group 1B: PD-L1 1-49%, Pembrolizumab run-in population; Group 2A: PD-L1 ≥ 50%, Main Study Population; Group 2B: PD-L1 ≥ 50%, Pembrolizumab run-in population

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be to be eligible to participate in this study, an individual must meet all of the following criteria:
• Histologically or cytologically confirmed non-squamous NSCLC that is metastatic (Stage IV), recurrent, or unresectable locally advanced (Stage IIIB/IIIC) disease, not amenable to treatment with curative intent.
• No prior systemic therapy for advanced disease. Prior chemotherapy for local or locally advanced disease is allowed if completed \>6 months prior to trial enrollment. Prior immunotherapy is not allowed.
• PD-L1 ≥ 1% using the 22c3 PD-L1 IHC assay or a local assay performed in a CLIA facility
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Life expectancy of at least 3 months.
• Measurable disease as per RECIST v1.1
• Adequate bone marrow and organ function demonstrated by:
• Absolute neutrophil count \>1,500/mm3 (1.5 × 10\^9/L).
• Hemoglobin ≥ 8.0 g/dL not dependent on transfusion support.
• Platelet count ≥ 75 × 10\^9/L (≥ 75,000 per mm3).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN without liver metastases; \< 5.0 x ULN if documented liver metastases
• Serum total bilirubin ≤ ULN, or for patients with potential Gilbert's, direct bilirubin ≤ ULN
• Calculated creatinine clearance ≥ 40 mL/min, using the Cockcroft-Gault formula.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Symptomatic or untreated brain metastases ≥ 2cm in diameter. Patients with brain lesions that are adequately treated with local therapy (i.e. radiation therapy) and neurologically stable without the need for corticosteroids for at least 2 weeks prior to enrollment are allowed. Patients with brain lesions that are asymptomatic, smaller than 2cm, in non-critical regions of the brain and not requiring corticosteroids for at least 2 weeks prior to enrollment may be eligible after review with the Sponsor Investigator.
• Leptomeningeal disease
• Known mutations/alterations in EGFR, ROS1, ALK, or BRAF
• Any prior treatment with checkpoint inhibitor therapy or other immunotherapy agents
• Any prior treatment with therapy having the same mechanism of action as sitravatinib (e.g., tyrosine kinase inhibitor with a similar target profile or bevacizumab/ramucirumab)
• Active or prior documented autoimmune disease within the past 2 years (note: patients with type 1 diabetes, vitiligo, Graves' disease, hypothyroidism due to an autoimmune condition only requiring hormone replacement, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded).
• Active or prior immunocompromising conditions, including use of immunosuppressive medication within 2 weeks of enrollment. This does not include topical, intranasal or inhaled steroids with minimal systemic absorption or systemic corticosteroids at physiologic doses not to exceed 10mg/day of prednisone or equivalent. Use of higher dose corticosteroids for short/defined course (ie prophylaxis in patients with contrast dye allergy) is also allowed if indicated.
• Uncontrolled HIV. Patients with HIV may be eligible if they meet the following criteria:
• CD4+ T cell count\>350 cell/uL
• No history of AIDS-defining opportunistic infection within the past 12 months
• Currently tolerating treatment with ART for at least 4 weeks prior to enrollment, with HIV viral load \<400 copies/mL
• Patients on specific ART drugs with possibility for drug-drug interaction with sitravatinib may be excluded (see appendix 5).
• Active hepatitis C (HCV) infection. Patients with a history of HCV may be eligible if they have completed curative antiviral treatment with undetectable HCV viral load and liver function tests are otherwise within acceptable limits (as described in Section 4.5.2). Patients with chronic Hepatitis B (HBV) infection are not excluded if liver function is within acceptable limits, but should be evaluated for reactivation risk and started on suppressive antiviral therapy prior to enrollment if appropriate.
• History of stroke or transient ischemic attack within the previous 6 months.

Sponsors & Collaborators

• Sarah Goldberg: lead
• Mirati Therapeutics Inc.: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Diseases; Lung Neoplasms

Interventions

sitravatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases

Results Point of Contact

• Title: Sarah Goldberg, MD, MPH: Associate Professor of Internal Medicine (Medical Oncology)
• Organization: Yale School of Medicine

sarah.goldberg@yale.edu

(203) 200-5864

Study Officials

• Sarah Goldberg, MD MPH

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Internal Medicine (Medical Oncology)

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 14, 2021
• Study Start: February 10, 2022
• Primary Completion: June 22, 2023
• Study Completion: October 30, 2023
• Last Updated: April 17, 2025
• Results First Posted: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)