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

Tislelizumab Plus Sitravatinib or Anlotinib as Maintenance Therapy in Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) (IASLC-WCLC 2025) - "Conclusions : TIS plus Sitra or Anlo yielded promising efficacy with manageable toxicities as maintenance therapy in ES-SCLC patients after induction TIS + chemo. This enhanced maintenance strategy warrants further exploration in larger-scale trials."

Clinical • Cardiovascular • Fatigue • Hypertension • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Mechanistic Study of Osimertinib Combined With Sitravatinibto Overcome Acquired Osimertinib Resistance in Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "The combined therapy may overcome resistance by simultaneously inhibiting anti-apoptotic mechanisms, inducing pyroptosis, and targeting the TGF-β/SMAD/SNAIL axis to suppress the EMT process. These findings provide novel insights and potential therapeutic strategies for the treatment of NSCLC after the development of resistance to osimertinib."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDH2 • CTNNB1 • NLRP3 • TGFB1 • TRAF1 • VIM

Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas. (PubMed, Commun Biol) - "We demonstrate that the mTKI sitravatinib rapidly induces collateral sensitivity to the FGFR inhibitor infigratinib which can be exploited for adaptive therapy to suppress STS cell growth. This study provides proof-of-principle that collateral sensitivity may be an effective strategy for overcoming resistance to mTKIs and this novel approach should be explored in the design of future trials."

Journal • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

SAPPHIRE: Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=577 | Active, not recruiting | Sponsor: Mirati Therapeutics Inc. | Trial completion date: Jun 2025 ➔ Oct 2025

Checkpoint inhibition • Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Sitravatinib combined with venetoclax exerts effective synergy to eliminate acute myeloid leukemia cells with FLT3-ITD mutations. (PubMed, Transl Oncol) - "The combination of venetoclax and FLT3 inhibitors gilteritinib and quizartinib has shown promising results in reducing leukemia burden and improving survival in pre-clinical studies and clinical trials of AML with FLT3 mutation. Finally, we tested the potential application of sitravatinib plus venetoclax in vivo using patient-derived xenografts, and found that the combined therapy was significantly more effective in inhibiting leukemia cell expansion, reducing infiltration in the spleen, and prolonging survival time compared to a single administration. Our study demonstrates the potential use of sitravatinib plus venetoclax as an alternative therapeutic strategy to treat AML patients with FLT3-ITD mutation."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • FLT3 • MCL1

Tislelizumab and sitravatinib as adjuvant therapy for hepatocellular carcinoma patients at high risk of recurrence following surgical resection: A multi-center, non-randomized, open-label phase 2 study. (ASCO 2025) - P2 | "The IMbrave 050 trial suggested that adjuvant atezolizumab plus bevacizumab might delay recurrence-free survival (RFS) in patients with resected or ablated hepatocellular carcinoma with high-risk of recurrence, highlighting the benefits of checkpoint inhibitor combining anti-angiogenesis agent in preventing or delaying recurrence after curative resection. Tislelizumab plus sitravatinib yielded clinically promising efficacy and had manageable safety profile as adjuvant therapy in HCC patients with high risk of recurrence. Continued follow-up is ongoing to assess the long-term efficacy and safety of this combination strategy."

Clinical • P2 data • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Respiratory Diseases • Solid Tumor

National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=423 | Active, not recruiting | Sponsor: University of Birmingham | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

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

SITISVEAL: Sitravatinib and Tislelizumab in Patients With Metastatic Uveal Melanoma With Liver Metastases. (clinicaltrials.gov) - P2 | N=16 | Completed | Sponsor: Grupo Español Multidisciplinar de Melanoma | Active, not recruiting ➔ Completed

Trial completion • Eye Cancer • Oncology • Solid Tumor • Uveal Melanoma

Sitravatinib targets TYRO3 to augment the anti-tumor immune response of PD-1 blockade in hepatocellular carcinoma. (PubMed, Clin Cancer Res) - "Collectively, we demonstrated a rationale for combining sitravatinib with PD-1 blockade in the treatment for HCC."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • AXL • CD8 • IL33 • MERTK • MET • STAT1 • TYRO3

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

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: BeiGene | N=300 ➔ 430

Enrollment change • 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

SAPPHIRE: Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=577 | Active, not recruiting | Sponsor: Mirati Therapeutics Inc. | Trial completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

SITISVEAL: Sitravatinib and Tislelizumab in Patients With Metastatic Uveal Melanoma With Liver Metastases. (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor: Grupo Español Multidisciplinar de Melanoma | Trial completion date: May 2024 ➔ Aug 2025

Trial completion date • Eye Cancer • Oncology • Solid Tumor • Uveal Melanoma

Mechanistic Investigation of Sitravatinib's Therapeutic Potential in Hepatic Fibrosis: A Comprehensive Analysis of Function and Molecular Pathways (APASL 2025) - "Our comprehensive investigation provides compelling evidence that sitravatinib demonstrates significant efficacy in alleviating liver fibrosis. These findings strongly support its potential as a promising therapeutic intervention for the treatment of hepatic fibrosis, warranting further investigation in clinical settings. Table and Figure:Figure 1.Figure 1."

Fibrosis • Hepatitis C • Hepatology • Immunology • Inflammation • Liver Cirrhosis • COL1A1 • TGFB1 • ZEB2

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

Sitravatinib + Nivolumab + Ipilimumab for #ccRCC: 45.5% response rate 86.4% disease control 1-yr OS: 80.8% @pavlosmsaouel Excellent translational insights via scRNA-seq reveal resistance (T-cell exhaustion, M2-like myeloid cell). DOI:10.1038/s41467-024-55642-8

Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial (Nature, Nat Commun) - P1/1b | N=22 | NCT04518046 | Sponsor: Mirati Therapeutics Inc. | "Overall, the triplet combination achieved ORR 45.5%, DCR 86.4%, median PFS 14.5 months, and 1-year survival 80.8%. Median OS and DOR were not reached. Sitravatinib exposure increased dose-dependently. Single-cell RNA-seq of longitudinally collected tumor biopsies from 12 patients identified a tumor cell-specific epithelial-mesenchymal transition-like program associated with treatment resistance and poor outcomes. Treatment resistance was characterized by a transition from cytotoxic to exhausted T cell state and enrichment for M2-like myeloid cells."

P1 data • Clear Cell Renal Cell Carcinoma

Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial (Nature, Nat Commun) - P1/1b | N=22 | NCT04518046 | Sponsor: Mirati Therapeutics Inc. | "Overall, the triplet combination achieved ORR 45.5%, DCR 86.4%, median PFS 14.5 months, and 1-year survival 80.8%. Median OS and DOR were not reached. Sitravatinib exposure increased dose-dependently. Single-cell RNA-seq of longitudinally collected tumor biopsies from 12 patients identified a tumor cell-specific epithelial-mesenchymal transition-like program associated with treatment resistance and poor outcomes. Treatment resistance was characterized by a transition from cytotoxic to exhausted T cell state and enrichment for M2-like myeloid cells."

P1 data • Clear Cell Renal Cell Carcinoma

SNAPI: Sitravatinib and Nivolumab for the Treatment of Metastatic or Advanced Clear Cell Renal Cell Cancer (clinicaltrials.gov) - P2 | N=88 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jan 2025 ➔ Jan 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2027

Metastases • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • 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

Detailed characterization of combination treatment with MET inhibitor plus EGFR inhibitor in EGFR-mutant and MET-amplified non-small cell lung cancer. (PubMed, Transl Lung Cancer Res) - "One MET D1246H-mutant case and one EGFR C797S-mutant case responded to sitravatinib and amivantamab, respectively. Pneumonitis was the main adverse effects leading to treatment discontinuation. Early discontinuation of METi negatively affected the survival outcomes."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • 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

Sitravatinib in patients with solid tumors selected by molecular alterations: results from a Phase Ib study. (PubMed, Future Oncol) - P1 | "Most treatment-emergent adverse events were mild-to-moderate in severity. The study closed before the planned number of patients were enrolled in all cohorts. Sitravatinib had a manageable safety profile with modest signals of clinical activity in patients with molecularly selected solid tumors.Clinical trial registration: www.clinicaltrials.gov identifier is NCT02219711."

Journal • P1 data • Cardiovascular • Fatigue • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • DDR2 • KDR • NTRK • PDGFRA

Sitravatinib Plus Nivo-Ipi Appears Safe, Active in ccRCC (Cancer Therapy Advisor) - P1/1b | N=22 | NCT04518046 | Sponsor: Mirati Therapeutics Inc. | "Among the 7 patients who received sitravatinib at 35 mg daily plus nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks, 1 patient experienced a dose-limiting toxicity of grade 3 myositis/myasthenia gravis....Overall, the objective response rate (ORR) was 45.5%, and the disease control rate was 86.4%. The median progression-free survival was 14.5 months, and 72.7% of patients were still alive at a median follow-up of 15.7 months."

Clear Cell Renal Cell Carcinoma