Sitravatinib in patients with solid tumors selected by molecular alterations: results from a Phase Ib study
<b>Aim:</b> 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.<b>Materials & methods:</b> Patients with advanced solid tumors harboring amplification, mutation, or rearrangement of <i>MET</i>, <i>AXL</i>, <i>RET</i>, <i>NTRK</i>, <i>DDR2</i>, <i>KDR</i>, <i>PDGFRA</i>, <i>KIT</i> or <i>CBL</i> received sitravatinib once daily. Primary end point was confirmed objective response rate (ORR).<b>Results:</b> In total, 113 patients were enrolled following a median of 3 (range 1-18) prior systemic regimens. Altered <i>RET</i> (n = 31), <i>CBL</i> (n = 31) and <i>MET</i> (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 <i>RET</i>-rearranged non-small cell lung cancer (21.1%) but did not differ significantly from the null hypothesis (ORR ≤15%; <i>p</i> = 0.316). Median progression-free survival and overall survival (5.7 and 24.2 months, respectively) were also longest in the <i>RET</i>-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 mild-to-moderate in severity. The study closed before the planned number of patients were enrolled in all cohorts.<b>Conclusion:</b> 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.
Authors
- Judy S Wang
- Saskia Neuteboom
- Collin M. Blakely (ORCID: https://orcid.org/0000-0001-8134-3651)
- Sanjay Goel (ORCID: https://orcid.org/0000-0002-2798-7568)
- Lyudmila Bazhenova (ORCID: https://orcid.org/0000-0001-8764-4359)
- Todd Michael Bauer (ORCID: https://orcid.org/0000-0002-3078-5043)
- Theresa L. Werner (ORCID: https://orcid.org/0000-0003-3868-7795)
- Keith D. Eaton (ORCID: https://orcid.org/0000-0001-5025-2001)
- Douglas R. Adkins (ORCID: https://orcid.org/0000-0003-3207-8227)
- Rebecca S. Heist (ORCID: https://orcid.org/0000-0002-7397-2009)
- Byoung Chul Cho (ORCID: https://orcid.org/0000-0002-5562-270X)
- James G. Christensen (ORCID: https://orcid.org/0000-0003-1835-0335)
- Shubham Pant (ORCID: https://orcid.org/0000-0001-9281-480X)
- Richard C. Chao (ORCID: https://orcid.org/0000-0002-6325-9592)
- Dong‐Wan Kim (ORCID: https://orcid.org/0000-0001-5124-7132)
- Xiaohong Yan
Institutions
- Montefiore Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of California, San Francisco (US)
- Yonsei University (KR)
- University of Washington (US)
- Washington University in St. Louis (US)
- University of Utah (US)
- Huntsman Cancer Institute (US)
- Seoul National University Hospital (KR)
- University of California San Diego (US)
- Massachusetts General Hospital (US)
- Fred Hutch Cancer Center (US)
- Sarah Cannon (US)
- Mirati Therapeutics (United States) (US)
- Florida Cancer Specialists & Research Institute (US)
- Tennessee Oncology (US)
Publication Details
- Journal
- Future Oncology
- Published
- 2024-11-08
- DOI
- https://doi.org/10.1080/14796694.2024.2418285
- Citations
- 1
- Primary Topic
- Chronic Myeloid Leukemia Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.45
Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- Gilead Sciences
- Regeneron Pharmaceuticals
- Agios Pharmaceuticals
- Mersana Therapeutics
- Mirati Therapeutics
- BeiGene
- Yuhan
- Daiichi-Sankyo
- European Society for Medical Oncology
- LG Chem
- Daiichi Sankyo Europe