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

Area of Science:

• Oncology
• Molecular Biology
• Clinical Pharmacology

Background:

• Advanced solid tumors often harbor specific molecular alterations driving oncogenesis.
• Targeted therapies offer potential treatment avenues for patients with these genetic profiles.
• Sitravatinib is an investigational tyrosine kinase inhibitor targeting multiple receptor tyrosine kinases.

Purpose of the Study:

• To evaluate the clinical activity and safety of sitravatinib in patients with advanced solid tumors.
• To assess response rates in specific molecularly defined patient cohorts.
• To identify potential patient populations that may benefit from sitravatinib treatment.

Main Methods:

• Phase Ib basket study design.
• Enrollment of 113 patients with advanced solid tumors and specific molecular alterations (MET, AXL, RET, NTRK, DDR2, KDR, PDGFRA, KIT, CBL).
• Sitravatinib administered orally once daily; primary endpoint was objective response rate (ORR).

Main Results:

• Most frequent alterations: RET (n=31), CBL (n=31), MET (n=17).
• Overall, 68.9% experienced tumor volume reduction; 61.5% had best objective response of stable disease.
• Highest ORR (21.1%) observed in RET-rearranged non-small cell lung cancer (NSCLC), though not statistically significant compared to null hypothesis.
• Median progression-free survival (5.7 months) and overall survival (24.2 months) were longest in the RET-rearranged NSCLC cohort.
• Most frequent treatment-emergent adverse events included diarrhea (61.1%), fatigue (50.4%), and hypertension (46.9%), generally mild-to-moderate.

Conclusions:

• Sitravatinib demonstrates a manageable safety profile in patients with molecularly selected advanced solid tumors.
• Modest clinical activity was observed, with particular interest in the RET-rearranged NSCLC cohort.
• Further investigation may be warranted for sitravatinib in specific molecularly defined cancer populations.