Date: 2017-01-05
Type of information: Interim results
phase: 1b
Announcement: interim results
Company: Mirati Therapeutics (USA - CA)
Product: sitravatinib (MGCD516)
Action
mechanism: kinase inhibitor/tyrosine kinase inhibitor. MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families.
Disease: advanced solid tumors
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles. During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled. (NCT02219711)
Latest
news: * On January 5, 2017, Mirati Therapeutics announced data from the Phase 1b trial of sitravatinib, a receptor tyrosine kinase inhibitor for the treatment of genetically-selected NSCLC and other solid tumors. * On December 17, 2015, Mirati Therapeutics announced that the first patient with non-small cell lung cancer (NSCLC) has been dosed in a Phase 1b clinical trial of MGCD516. The trial will evaluate select patients exhibiting genetic alterations in the tyrosine kinase signaling pathways, RET, DDR and Trk, which are known oncogenic drivers. The study will also explore other mechanisms that may play a role in regulating tumor growth, including selecting for patients with CBL mutations and chromosome 4 amplicon alterations.
Sitravatinib is being evaluated in a Phase 1b expansion trial designed to evaluate its safety and efficacy in multiple pre-specified cohorts of cancer patients with genetic mutations involving sitravatinib targets, including a cohort of NSCLC patients with RET fusion mutations. As of a data cut-off of December 9, 2016, a total of six NSCLC patients with RET fusion mutations had been enrolled, four of whom were evaluable:
Of the four evaluable patients, one patient with a KIF5-B RET fusion demonstrated a confirmed PR and one patient with a DSP RET fusion has achieved an unconfirmed PR on initial scan, representing a 50% ORR, including confirmed and unconfirmed responses. Both patients remain on study. A third patient with RET fusion demonstrated tumor reduction of 29%, representing stable disease. Tumor reduction was observed in in all four patients. The longest duration on study is more than 46 weeks and the patient remains on study.
The Phase 1b trial is also enrolling NSCLC patients with CBL mutations, CHR4q12 amplification, and AXL alterations. As of the data cut-off date, no patients with these genetic mutations were evaluable.
The Company expects to provide an additional update on the sitravatinib program in Q3 2017.
The purpose of the Phase 1b open-label trial is to evaluate the safety and efficacy of 150 mg once-daily (QD) MGCD516, administered orally, in patients with the genetic driver alterations of interest, including RET fusions, DDR mutations, Trk fusions and Trk mutations, CBL mutations and CHR4q12 gene amplification. The trial will enroll patients with NSCLC as well as patients with advanced solid tumors that carry the genetic alterations of interest.
