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Carcinoma, Non-Small-Cell LungPhase 2NCT04925986

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

A Phase 2 study testing Sitravatinib and Pembrolizumab in people with Carcinoma, Non-Small-Cell Lung and Lung Diseases, run by Sarah Goldberg at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sitravatinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
10 Feb 2022to 30 Oct 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 19Show fewer
  • 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.
  • 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.
  • Completed informed consent process, including signing IRB approved informed consent form.
  • Willing to comply with clinical trial instructions and requirements.
  • Willing to undergo an on-treatment biopsy with an appropriate biopsy site identified prior to treatment initiation

Who cannot join

  • 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)
Show all 29Show fewer
  • 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.
  • History of life threatening venous thromboembolic event (such as hemodynamically significant pulmonary embolism) or any arterial thrombotic event within the previous 6 months. Patients with non-life threatening venous thromboembolic events are not excluded and should be managed with anti-coagulation as per standard institutional practice.
  • Any of the following cardiac abnormalities:
  • Unstable angina pectoris within the past 6 months.
  • Congestive heart failure ≥ NYHA Class 3 within the past 6 months.
  • Prolonged QTc on electrocardiogram >500 milliseconds.
  • Left ventricular ejection fraction (LVEF) < 40%.
  • Uncontrolled hypertension (>150mm Hg or >100mm Hg diastolic) on multiple observations despite standard of care treatment
  • Major surgery within 4 weeks of the date of randomization.
  • History of significant hemoptysis or hemorrhage within 4 weeks of the date of randomization.
  • Known or suspected presence of another malignancy that could be mistaken for the malignancy under study during disease assessments.
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  • Pregnancy. WOCBP must have a negative serum or urine pregnancy test documented within the screening period prior to the date of randomization.
  • Breast-feeding or planning to breast-feed during the study or within 30 days following the last dose of sitravatinib and within 5 months following the last dose of pembrolizumab.
  • Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Yale University

    New Haven, Connecticut, 06520

Other trials in United States

About this study

Official title: Phase 2 Trial of Sitravatinib Plus Pembrolizumab in Patients With Advanced Treatment-Naïve PD-L1+ Non-Squamous Non-Small Cell Lung Cancer

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.

Read the detailed 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. For clinical analysis, there will be two patient cohorts defined by PD-L1 status: Cohort 1 for patients with PD-L1 Tumor Proportion Score (TPS) 1-49% and Cohort 2 for patients with TPS≥50%. The investigators will implement a Simon's two-stage design to evaluate the efficacy of sitravatinib in combination with pembrolizumab for each cohort separately.

There will be two groups within each cohort of this study: the "main study population" (Group A) in which patients will receive pembrolizumab plus sitravatinib beginning on Cycle 1 Day 1 (C1D1), and a "pembrolizumab run-in population" (Group B) in which patients will receive pembrolizumab alone for 1 dose followed by pembrolizumab plus sitravatinib beginning C2D1.

The primary endpoint of the trial is the ORR for patients treated with pembrolizumab plus sitravatinib in the main study population. The purpose of the pembrolizumab run-in population is to obtain tissue and blood samples from these patients to be used as controls for correlative studies and to determine the preliminary efficacy of pembrolizumab alone followed by the combination.

Primary Objective

(1) The primary objective of this study is to evaluate the efficacy of sitravatinib in combination with pembrolizumab in the front-line treatment of patients with advanced non-squamous PD-L1 positive NSCLC by measuring Objective Response Rate (ORR).

Secondary Objectives

  1. To evaluate other measures of efficacy including Overall Survival (OS), Progression Free Survival (PFS), Duration of Response (DOR) and Clinical Benefit Rate (CBR) in the first-line setting for patients with advanced, non-squamous, PD-L1 positive NSCLC treated with the combination of sitravatinib and pembrolizumab.
  2. To evaluate the toxicity profile and tolerability of sitravatinib/pembrolizumab in advanced, treatment naïve, non-squamous, PD-L1 positive NSCLC.

Exploratory Objectives:

  1. To evaluate ORR, OS, PFS, DOR, and CBR in patients with advanced, non-squamous, treatment naïve, PD-L1 positive NSCLC who receive pembrolizumab run-in followed by pembrolizumab/sitravatinib combination therapy.
  2. To evaluate the CNS activity of sitravatinib/pembrolizumab in patients with advanced, treatment naïve, PD-L1 positive NSCLC by measuring Intracranial Objective Response Rate (iORR) and Intracranial Duration of Response(iDOR) in patients with baseline CNS disease, and Intercranial Progression-Free Survival (iPFS) in all patients.
  3. To study correlates of the adaptive and innate immune responses induced by sitravatinib and pembrolizumab treatment in both tumor tissue and peripheral blood.
  4. To explore the association between tumor immune contexture and clinical benefit to sitravatinib and pembrolizumab.
Being tested
Sitravatinib, Pembrolizumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Diseases, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SitravatinibDrug

    Also called IND 155305

    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).

  • PembrolizumabDrug

    Also called Keytruda

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

Study groups in NCT04925986
Study groupRoleWhat they receive
Group 1A: PD-L1 1-49%, Main Study PopulationExperimentalParticipants 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).
Receives: Drug: Sitravatinib; Drug: Pembrolizumab
Group 1B: PD-L1 1-49%, Pembrolizumab run-in populationExperimentalParticipants 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.
Receives: Drug: Sitravatinib; Drug: Pembrolizumab
Group 2A: PD-L1 ≥ 50%, Main Study PopulationExperimentalParticipants 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).
Receives: Drug: Sitravatinib; Drug: Pembrolizumab
Group 2B: PD-L1 ≥ 50%, Pembrolizumab run-in populationExperimentalParticipants 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.
Receives: Drug: Sitravatinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: up to 267 days

Secondary outcomes (5)

  1. Overall Survival (OS)

    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

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

  2. Progression Free Survival (PFS)

    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.

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

  3. Duration of Response (DOR)

    Duration of Response (DOR) for patients in Group A is a secondary endpoints for this study; DOR for Group B is an exploratory endpoint. Defined as time that measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or to death due to any cause in the absence of documented PD.

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

  4. Clinical Benefit Rate (CBR)

    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

    Measured: up to 2 years

  5. Number of Participants That Experienced at Least 1 Adverse Event

    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.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2021
  2. Study start10 Feb 2022
  3. Primary completion22 Jun 2023
  4. Study completion30 Oct 2023

Why it stopped: Sponsor decision based on data from other clinical trials

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04925986
Sponsor's protocol ID
2000030093
Status last verified
Apr 2025
First submitted
8 Jun 2021
Last updated
17 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sitravatinib and Pembrolizumab in people with Carcinoma, Non-Small-Cell Lung and Lung Diseases, run by Sarah Goldberg at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: up to 267 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04925986.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2025.

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