sitravatinib (MGCD516) / BeOne Medicines, BMS - LARVOL DELTA

A phase II trial of sitravatinib + nivolumab after progression on immune checkpoint inhibitor in patients with metastatic clear cell RCC. (PubMed, Oncologist) - P2 | "In this small phase 2 trial with limited sample size due to early termination, sitravatinib plus nivolumab demonstrated a manageable safety profile and produced modest clinical benefit. The observed responses occurred in patients who did not receive prior treatment with cabozantinib or lenvatinib. (ClinicalTrials.gov Identifier: NCT04904302)."

Checkpoint inhibition • Journal • P2 data • Clear Cell Renal Cell Carcinoma • Oncology • Renal Cell Carcinoma

A phase II trial of sitravatinib plus nivolumab after progression on prior immune checkpoint inhibitor (ICI) in patients with metastatic clear cell renal cell carcinoma (ccRCC). (ASCO 2024) - P2 | " In this investigator-initiated, phase II, multicenter trial (NCT04904302), patients with progressive metastatic ccRCC after 1-2 lines of treatment were enrolled into three cohorts: Cohort A) progression on 1L nivolumab + ipilimumab, Cohort B) progression on 1L pembrolizumab + axitinib or 2L anti-PD-1 therapy after receiving 1L VEGF-targeted monotherapy, Cohort C) progression on 1L or 2L cabozantinib or lenvatinib +/- everolimus either before, after, or in combination with anti-PD-1 ICI... In this small phase 2 trial with limited sample size due to early termination, sitravatinib plus nivolumab demonstrated a manageable safety profile and produced modest clinical benefit. The observed responses occurred in patients who did not receive prior treatment with cabozantinib or lenvatinib."

Checkpoint inhibition • Clinical • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Sarcoma • Solid Tumor

Phase II study of sitravatinib in combination with tislelizumab in patients with advanced biliary tract cancer who have failed to at least 1 prior systemic treatment. (ASCO 2024) - P2 | "Sitravatinib/tiselizumab combination as 2L therapy in patients with advanced BTC demonstrated meaningful efficacy and an acceptable safety profile. Especially, patient selection using HRD biomarker might be a promising strategy in this setting."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Biliary Cancer • Biliary Tract Cancer • Cardiovascular • Dermatology • Gastrointestinal Cancer • Hypertension • Oncology • Solid Tumor • HRD

BGB-900-2001-IIT: A Phase II Study to Explore the Safety, Tolerability, and Preliminary Antitumor Activity of Sitravatinib Plus Tislelizumab or Combination With Nab-paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P2 | N=98 | Active, not recruiting | Sponsor: Fudan University | Trial completion date: Jun 2024 ➔ Jun 2027 | Trial primary completion date: Jun 2024 ➔ Jun 2026

Trial completion date • Trial primary completion date • Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

SAFFRON-301: Tislelizumab Plus Sitravatinib in Advanced/Metastatic NSCLC Progressing on/after Chemotherapy and Anti-PD-(L)1 (IASLC-WCLC 2024) - P3 | "We present efficacy/safety results from an open-label, randomized, phase 3 trial evaluating TIS plus sitra versus docetaxel (doc) in patients with previously treated locally advanced/metastatic NSCLC (NCT04921358). The trial was terminated due to safety risks/unfavorable benefit-risk analysis. Conclusions : In patients with previously treated advanced/metastatic NSCLC, TIS+sitra showed similar efficacy to doc and was associated with a higher incidence of TEAEs."

Metastases • Cardiovascular • Dermatology • Febrile Neutropenia • Hematological Disorders • Hypertension • Infectious Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

Tislelizumab plus sitravatinib and nab-paclitaxel in patients with untreated locally recurrent or metastatic triple negative breast cancer (TNBC): updated efficacy and safety results. (SABCS 2024) - P2 | "The triplet combination of Tisle, Sitra, and nab-P demonstrated clinically meaningful ORR and PFS with acceptable safety profile as first-line treatment for patients with untreated locally recurrent or metastatic TNBC. Notably, patients with CD8+ expression achieved impressive PFS, indicating that CD8 status might be a biomarker for efficacy prediction. Continued follow-up is being conducted to assess long-term survival and safety."

Clinical • IO biomarker • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8

Sitravatinib plus tislelizumab for metastatic uveal melanoma with liver metastasis: The open-label, multicenter, phase II GEM-2101 trial (ESMO 2024) - P2 | "This study aims to assess the efficacy of the combination of sitravatinib (sitra), a pan-TKI inhibitor (targeting RET, the TAM family (TYRO3, AXL and MER-TK), VEGFR2, and KIT), and tislelizumab (tisle), an anti-PD1 antibody designed to minimize the binding to Fcγ receptors, in patients with MUM and LM. This was a single-arm, phase II trial testing sitra and tisle (sitra+tisle) for systemic treatment-naïve patients or after failure to 1st line tebentafusp if HLA-A02:01. Sitra+tisle showed promising activity with a manageable toxicity profile in patients with MUM and LM. The PFS observed is the longest PFS ever reported for systemic treatment in MUM. An update on translational research to understand synergy between both drugs using correlative liver biopsies is underway."

Clinical • Metastases • P2 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • AXL • HLA-A • KDR

MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Non-Squamous Non-Small Cell Lung Cancer Progressing On/After Checkpoint Inhibitor Therapy or Chemotherapy. (PubMed, J Thorac Oncol) - "Sitravatinib with nivolumab had a manageable safety profile. Although ORR was not met, this combination demonstrated antitumor activity and encouraging survival in CPI-experienced patients with non-squamous NSCLC."

Checkpoint inhibition • Journal • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KDR

A phase 1-2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy. (PubMed, Sci Transl Med) - "In addition, correlative studies demonstrated reduction of immune-suppressive myeloid cells in the periphery and tumor microenvironment following sitravatinib treatment. This study provides a rationally designed combinatorial strategy to improve outcomes of anti-PD-1 therapy in advanced ccRCC."

Journal • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Patient-Derived Cell-Based Functional Drug Sensitivity Predicts Response Heterogeneity and Early Progression in EGFR-Mutant NSCLC (IASLC-WCLC 2026) - "In addition, multikinase inhibitors, such as sitravatinib targeting TAM receptors (TYRO3, AXL, MERTK) and VEGFR, showed a trend toward increased sensitivity in the EF group, suggesting potential alternative therapeutic vulnerabilities. Conclusions : PDC-based functional drug sensitivity captures clinically relevant heterogeneity in response to osimertinib and independently predicts early disease progression in EGFR-mutant NSCLC. This approach may enable prospective identification of patients unlikely to benefit from EGFR-TKI monotherapy and support personalized upfront treatment strategies."

Clinical • Heterogeneity • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • AXL • EGFR • MERTK • TP53

A Phase 2 Study of Sitravatinib in Combination with Nivolumab in Patients with Advanced or Metastatic Urothelial Carcinoma. (PubMed, Eur Urol Oncol) - P2 | "Sitravatinib plus nivolumab demonstrated a manageable safety profile but did not result in clinically meaningful ORRs in patients with advanced/metastatic UC in the eight cohorts studied."

Combination therapy • Journal • Metastases • P2 data • Bladder Cancer • Cardiovascular • Congestive Heart Failure • Genito-urinary Cancer • Heart Failure • Oncology • Solid Tumor • Urothelial Cancer • AXL • KDR • MERTK

Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial. (PubMed, Nat Commun) - P1 | "The observed hypothesis-generating changes in gene expression dynamics and cellular states may help inform future strategies to optimize immunotherapy efficacy. Clinical Trials.gov identifier: NCT04518046."

IO biomarker • Journal • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor

SAPPHIRE: Phase III study of sitravatinib plus nivolumab versus docetaxel in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC) (ESMO 2023) - P3 | "Conclusions The primary endpoint of OS was not met in pts with previously treated adv nsq NSCLC. Safety profiles for sitra/nivo and doce were consistent with prior reports for each regimen."

Clinical • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

A single-arm phase 2 trial of Sitravatinib in advanced well-differentiated/dedifferentiated liposarcoma. (PubMed, Clin Cancer Res) - "Sitravatinib provided a progression-free rate at 12 weeks of 41% and meaningful disease control in a subset of patients with advanced, progressive WD/DD LPS."

Journal • Metastases • P2 data • Cardiovascular • Hypertension • Liposarcoma • Mucositis • Oncology • Otorhinolaryngology • Sarcoma • Solid Tumor

Phase 1 Study of Sitravatinib Combined with Nivolumab and Ipilimumab in Patients with Advanced Clear Cell Renal Cell Carcinoma: Clinical Outcomes and Translational Correlatives (IKCS 2024) - P1 | "The observed changes in gene expression and cellular states highlight potential biomarkers for resistance and may guide future strategies to enhance ICT effectiveness in ccRCC. ClinicalTrials.gov Identifier: NCT04518046"

Clinical • Clinical data • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • CNS Disorders • Genito-urinary Cancer • Immunology • Myasthenia Gravis • Myositis • Oncology • Solid Tumor

Single-cell transcriptomic insights into tumor and immune dynamics driving resistance to sitravatinib, nivolumab, and ipilimumab in advanced clear cell renal cell carcinoma (AACR 2025) - "The identification of a tumor-specificC8 signature provides a potential biomarker for predicting poor responses and tailoring therapeutic strategies. Further validation in larger cohorts is needed to optimize patient selection and therapeutic outcomes."

IO biomarker • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Comparative efficacy of immune checkpoint inhibitor–anti-VEGF inhibitor combinations in non–small cell lung carcinoma: A network meta-analysis of randomized trials. (ASCO 2026) - "Furthermore, nivolumab combined with sitravatinib demonstrated significantly superior OS and PFS compared with ramucirumab and chemotherapy...For ORR, pembrolizumab plus lenvatinib ranked highest, followed by atezolizumab plus bevacizumab. Nivolumab-based ICI and anti-VEGF combinations, particularly with bevacizumab and sitravatinib, demonstrate the most favorable survival outcomes in NSCLC. Evidence for ORR remains limited, and further randomized comparisons are required to better define the relative efficacy of these combinations."

Checkpoint inhibition • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-1

BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov) - P3 | N=404 | Completed | Sponsor: BeOne Medicines | Active, not recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor

National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=423 | Completed | Sponsor: University of Birmingham | Active, not recruiting ➔ Completed

IO biomarker • Trial completion • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • NKX2-1 • TP63

Selective Mcl-1 inhibition with KS18 overcomes apoptotic resistance and enhances FLT3-targeted therapy in acute myeloid leukemia (AACR 2026) - "Here, we evaluate KS18, a highly selective small-molecule Mcl-1 inhibitor developed in our laboratory, as a single agent and in rational drug combinations in AML models (MOLM-13, MV4-11, THP-1) including a venetoclax-resistant line (MV4-11 VR)...Combination treatment with either the FLT3 inhibitor quizartinib or the multi-kinase inhibitor sitravatinib yielded strong synergistic cytotoxicity through concurrent Mcl-1 suppression and inhibition of upstream survival pathways including FLT3/STAT5, AKT, and ERK...Together, these findings identify KS18 as a promising next-generation therapeutic candidate with both single-agent efficacy and strong combination potential for overcoming drug resistance and relapse in AML. Ongoing studies are generating FLT3 inhibitor-resistant models and evaluating KS18 in vivo across diverse FLT3 mutation backgrounds to accelerate its translational development for relapsed and refractory AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • FLT3 • STAT5

Lipid-based nanoparticle combination immunotherapy with sitravatinib for the systemic treatment of high-risk neuroblastoma (AACR 2024) - "Here, we have proposed and tested an immunotherapy with great promise for treating neuroblastoma. However, the impact of nanoparticle-based immunotherapy reaches far beyond neuroblastoma: it has the potential to be a platform for the development of immunotherapies specific to other highly metastatic cancer types."

Neuroblastoma • Oncology • Solid Tumor • DDR2 • IFNB1 • STING

BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov) - P3 | N=404 | Active, not recruiting | Sponsor: BeOne Medicines | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov) - P3 | N=430 | Enrolling by invitation | Sponsor: BeOne Medicines | Trial completion date: Dec 2026 ➔ Jul 2026 | Trial primary completion date: Dec 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

SNAPI: Sitravatinib and Nivolumab for the Treatment of Metastatic or Advanced Clear Cell Renal Cell Cancer (clinicaltrials.gov) - P2 | N=15 | Terminated | Sponsor: M.D. Anderson Cancer Center | N=88 ➔ 15 | Trial completion date: Jan 2027 ➔ Mar 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2027 ➔ Mar 2026; <75% participation

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

SAFFRON-301: a randomised phase III study of sitravatinib in combination with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer. (PubMed, BMJ Oncol) - P3 | "Patients were randomised 1:1 to receive sitravatinib 100 mg orally once daily plus tislelizumab 200 mg intravenously once every 3 weeks or docetaxel 75 mg/m2 intravenously every 3 weeks. Due to immature survival data, efficacy results should be interpreted with caution. NCT04921358."

IO biomarker • Journal • P3 data • Cardiovascular • Dermatology • Hematological Disorders • Hypertension • Infectious Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor