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NCT04925986

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

Terminated Phase 2 Results posted Last updated 17 April 2025
What this trial tests

Phase 2 trial testing Sitravatinib in Carcinoma, Non-Small-Cell Lung in 9 participants. Terminated before completion.

Timeline
10 February 2022
Primary endpoint
22 June 2023
30 October 2023

Quick facts

Lead sponsorSarah Goldberg
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment9
Start date10 February 2022
Primary completion22 June 2023
Estimated completion30 October 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Sarah Goldberg

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung or Lung Diseases. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Primary · up to 267 days

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)

GroupValue95% CI
Sitravatinib: Group 1A0
Sitravatinib: Group 2A0
Sitravatinib: Group 1B0
Sitravatinib: Group 2B0
Sitravatinib: Group 1A0
Sitravatinib: Group 2A0
Sitravatinib: Group 1B1
Sitravatinib: Group 2B1
Sitravatinib: Group 1A1
Sitravatinib: Group 2A2
Sitravatinib: Group 1B0
Sitravatinib: Group 2B2
Sitravatinib: Group 1A0
Sitravatinib: Group 2A0
Sitravatinib: Group 1B1
Sitravatinib: Group 2B0
Overall Survival (OS) Secondary · until death or date of last contact, up to 2 years

Overall Survival (OS) in the main study populations (ie groups 1A and 2A) is a secondary endpoint for this study. OS in groups 1B and 2B is an exploratory endpoint. Defined as the time from date of treatment start to death due to any cause

GroupValue95% CI
Sitravatinib: Group 1A246NA – NA
Sitravatinib: Group 2A21024 – NA
Progression Free Survival (PFS) Secondary · Until progressive disease, death, or last contact, up to 2 years

Progression Free Survival (PFS) in the main study populations (ie groups 1A and 2A) is a secondary endpoint for this study. PFS in groups 1B and 2B is an exploratory endpoint. Defined as time from first dose to first progressive disease (PD) or death due to any cause in the absence of documented PD.

GroupValue95% CI
Sitravatinib: Group 1A246NA – NA
Sitravatinib: Group 2A21024 – NA
Clinical Benefit Rate (CBR) Secondary · up to 2 years

Clinical Benefit Rate (CBR) in Group A is a secondary endpoints for this study, while CBR in Group B is an exploratory endpoint. Defined as percent of patients documented to have a confirmed Complete Response (CR), confirmed Partial Response (PR), or Stable Disease (SD) documented on at least 1 on-study assessment and including at least 5 weeks on study

GroupValue95% CI
Sitravatinib: Group 1A100
Sitravatinib: Group 2A66.7
Number of Participants That Experienced at Least 1 Adverse Event Secondary · 2 years

Evaluation of the safety and toxicity profile of the combination of sitravatinib and pembrolizumab in the first-line treatment of patients with non-squamous metastatic NSCLC is a secondary objective in this study. Secondary endpoint is adverse events as per CTCAE v.5. The Safety population is defined as all patients who received any dose of study treatment (i.e., sitravatinib and/or pembrolizumab) and will be used for all safety analyses. Number of participants that experienced at least 1 adverse event.

GroupValue95% CI
Sitravatinib: Group 1A1
Sitravatinib: Group 2A3
Sitravatinib: Group 1B2
Sitravatinib: Group 2B3

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 450 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sitravatinib: Group 1A
Serious: 1/1 (100%)
Deaths: 1/1
Sitravatinib: Group 2A
Serious: 2/3 (67%)
Deaths: 2/3
Sitravatinib: Group 1B
Serious: 2/2 (100%)
Deaths: 2/2
Sitravatinib: Group 2B
Serious: 1/3 (33%)
Deaths: 0/3

Serious adverse events (8 terms)

ReactionSystemSitravatinib: Group 1ASitravatinib: Group 2ASitravatinib: Group 1BSitravatinib: Group 2B
Lung infectionInfections and infestations
Myocardial infarctionCardiac disorders
MyocarditisCardiac disorders
Subarachnoid bleedingNervous system disorders
SeizureNervous system disorders
Thromboembolic eventVascular disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
CholecystitisHepatobiliary disorders
Other adverse events (96 terms — click to expand)

ReactionSystemSitravatinib: Group 1ASitravatinib: Group 2ASitravatinib: Group 1BSitravatinib: Group 2B
DiarrheaGastrointestinal disorders
HypothyroidismEndocrine disorders
Mucositis, oralGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Lung infectionInfections and infestations
Urinary tract infectionInfections and infestations
Alkaline phosphatase increasedInvestigations
ALT increasedInvestigations
AST increasedInvestigations
Weight lossInvestigations
HypocalcemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
HematuriaRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HoarsenessRespiratory, thoracic and mediastinal disorders
Palmar-Plantar ErythrodysesthesiaSkin and subcutaneous tissue disorders
Skin UlcerationSkin and subcutaneous tissue disorders
HypertensionVascular disorders
AnemiaBlood and lymphatic system disorders
Myocardial infarctionCardiac disorders
MyocarditisCardiac disorders
Sinus tachycardiaCardiac disorders
TachycardiaCardiac disorders
Ear painEar and labyrinth disorders
TinnitusEar and labyrinth disorders
Double visionEye disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
DysphagiaGastrointestinal disorders
VomitingGastrointestinal disorders
Chest painGeneral disorders
ChillsGeneral disorders
Edema of limbsGeneral disorders
Facial painGeneral disorders
Gait disturbanceGeneral disorders

Most-reported serious reactions: Lung infection, Myocardial infarction, Myocarditis, Subarachnoid bleeding, Seizure, Thromboembolic event, Pneumonitis, Cholecystitis.

Data from ClinicalTrials.gov NCT04925986 adverse events section.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. AXL in cancer: a modulator of drug resistance and therapeutic target.
    Tang Y, Zang H, Wen Q, Fan S. · · 2023 · cited 75× · PMID 37328828 · DOI 10.1186/s13046-023-02726-w
  2. Dissecting the Role of AXL in Cancer Immune Escape and Resistance to Immune Checkpoint Inhibition.
    Engelsen AST, Lotsberg ML, Abou Khouzam R, Thiery JP, et al · · 2022 · cited 74× · PMID 35572601 · DOI 10.3389/fimmu.2022.869676
  3. Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy.
    Gu Y, Zhang Z, Ten Dijke P. · · 2023 · cited 47× · PMID 36823234 · DOI 10.1038/s41423-023-00980-8
  4. AXL Inhibitors: Status of Clinical Development.
    Bhalla S, Gerber DE. · · 2023 · cited 46× · PMID 36920638 · DOI 10.1007/s11912-023-01392-7
  5. The Development of AXL Inhibitors in Lung Cancer: Recent Progress and Challenges.
    Sang YB, Kim JH, Kim CG, Hong MH, et al · · 2022 · cited 45× · PMID 35311091 · DOI 10.3389/fonc.2022.811247
  6. AXL signaling in cancer: from molecular insights to targeted therapies.
    Yadav M, Sharma A, Patne K, Tabasum S, et al · · 2025 · cited 42× · PMID 39924521 · DOI 10.1038/s41392-024-02121-7
  7. Two-Front War on Cancer-Targeting TAM Receptors in Solid Tumour Therapy.
    Mikolajczyk A, Mitula F, Popiel D, Kaminska B, et al · · 2022 · cited 13× · PMID 35626092 · DOI 10.3390/cancers14102488

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