Sitravatinib in patients with solid tumors selected by molecular alterations - results from a Phase Ib study

Sep 21, 2026

Aim: Clinical activity and safety of sitravatinib in advanced cancer were evaluated in basket cohorts defined by specific molecular alterations in a Phase Ib study. Patients with advanced solid tumors harboring MET, AXL, RET, NTRK, DDR2, KDR, PDGFRA, KIT, or CBL amplification, mutation, or rearrangement received sitravatinib once daily. Primary endpoint was confirmed objective response rate (ORR). In 113 enrolled patients, 68.9% showed reduced tumor volume; stable disease was the most common best response. ORR was highest in RET-rearranged non-small cell lung cancer (21.1%). Median progression-free survival and overall survival were 5.7 and 24.2 months, respectively. Diarrhea, fatigue, and hypertension were frequent; most events were mild to moderate.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Abstract

Aim

Materials & methods

Results

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FUTURE ONCOLOGY 2024, VOL. 20, NO. 39, 3213–3227 [https://doi.org/10.1080/14796694.2024.2418285](https://doi.org/10.1080/14796694.2024.2418285) RAPID COMMUNICATION Sitravatinib in patients with solid tumors selected by molecular alterations: results from a Phase Ib study Lyudmila Bazhenova* , a, Dong-Wan Kimb, Byoung Chul Choc, Sanjay Goel‡,d, Rebecca Heiste, Theresa L Wernerf, Keith D Eatong, Judy S Wangh, Shubham Panti, Douglas R Adkinsj, Collin M Blakelyk, Xiaohong Yan§,l, Saskia Neuteboom\# , l, James G Christensen\# , l, Richard Chaol and Todd Bauerm a University of California San Diego Moores Cancer Center, CA 92093, USA; b Seoul National University College of Medicine & Seoul National University Hospital, Seoul, Republic of Korea; cYonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; d Monteﬁore Medical Center, Bronx, NY 10467, USA; e Massachusetts General Hospital, Boston, MA 02114, USA; f Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; g University of Washington & Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; h Florida Cancer Specialists & Research Institute, Sarasota, FL 34232, USA; iUniversity of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; jWashington University School of Medicine in St Louis, MO 63110, USA; k University of California San Francisco, CA 94158, USA; l Mirati Therapeutics Inc., San Diego, CA 92121, USA; mSarah Cannon Research Institute, Tennessee Oncology, Nashville, TN 37203, USA ABSTRACT Aim: We report clinical activity and safety of sitravatinib in patients with advanced cancer from basket cohorts with specific molecular alterations, in a Phase Ib study. Materials & methods: Patients with advanced solid tumors harboring amplification, mutation, or rearrangement ofMET, AXL, RET, NTRK, DDR2, KDR, PDGFRA, KITor CBL received sitravatinib once daily. Primary end point was confirmed objective response rate (ORR) . Results: In total, 113 patients were enrolled following a median of 3 (range 1–18) prior systemic regimens. Altered RET (n = 31), CBL (n = 31) and MET (n = 17) were most frequent cohorts. Overall, 68.9% had reduced tumor volume and most (61.5%) had a best objective response of stable disease. ORR was highest in patients with RET-rearranged non-small cell lung cancer (21.1%) but did not differ significantly from the null hypothesis (ORR ≤ 15%; p = 0.316) . Median progression-free survival and overall survival (5.7 and 24.2 months, respectively) were also longest in theRET-rearranged non-small cell lung cancer cohort. Diarrhea (61.1%), fatigue (50.4%) and hypertension (46.9%) were the most frequent treatment-emergent adverse events. Most treatment-emergent adverse events were mildto-moderate in severity. The study closed before the planned number of patients were enrolled in all cohorts. Conclusion: Sitravatinib had a manageable safety profile with modest signals of clinical activity inpatients with molecularly selected solid tumors. Clinical trial registration: [www.clinicaltrials.gov](www.clinicaltrials.gov) identifier is NCT02219711 PLAIN LANGUAGE SUMMARY We report findings from a clinical study of sitravatinib which included patients with cancer that could not be removed by surgery or had spread to other parts of the body. The tumors of these patients contained specific molecular changes in one of the following genes: MET, AXL, RET, NTRK, DDR2, KDR, PDGFRA, KITor CBL. All patients received treatment with sitravatinib once a day. Change in tumor size over time was assessed to see how effective treatment with sitravatinib was. In total, 113 patients joined the study. Most patients had already received a median of three different types of medicines for their cancer (and up to 18 different types of anticancer medicines) . Most patients had tumors that contained alterations in RET, CBL or MET genes. During the study, the percentage of patients who had a decrease in the tumor size

FAQs

What was the purpose of the Phase Ib study of sitravatinib?

The study assessed clinical activity and safety of sitravatinib in patients with advanced cancer, using basket cohorts defined by specific molecular alterations.

Which patients were eligible and how was sitravatinib administered?

Patients had advanced solid tumors with amplification, mutation, or rearrangement in specified genes (including MET, AXL, RET, NTRK, DDR2, KDR, PDGFRA, KIT, or CBL) and received sitravatinib once daily.

What were the main efficacy and safety findings?

Overall, 68.9% had reduced tumor volume and most patients had stable disease. ORR was highest for RET-rearranged non-small cell lung cancer (21.1%). Diarrhea, fatigue, and hypertension were the most frequent adverse events, mostly mild to moderate.

Sep 21, 2026

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