Date: 2017-01-05
Type of information: Interim results
phase: 2
Announcement: interim results
Company: Mirati Therapeutics (USA - CA)
Product: glesatinib (MGCD265)
Action
mechanism: tyrosine kinase inhibitor. Glesatinib (MGCD265) is a tyrosine kinase inhibitor that potently and selectively targets tumors in patients with driver alterations in MET (mutations and gene amplification) and AXL (rearrangements and gene amplification) that occur in approximately 8% of patients with non-small cell lung cancer (NSCLC). Genetic alterations in these targets have been implicated as drivers of tumor growth and disease progression in NSCLC and other solid tumors.
Disease: non-small cell lung cancer (NSCLC)
Therapeutic area: Cancer - Oncology
Country: Australia, Canada, Hungary, Italy, Republic of Korea Poland, Taiwan, UK, USA
Trial
details: This study is a Phase 2 trial of MGCD265 in patients with locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC) that has activating genetic changes of the MET gene (mutation or amplification [increase number of gene copies]). Testing for tumor gene changes can be performed in tumor tissue or blood samples. Patients must have previously received treatment with chemotherapy. The number of patients to be enrolled will depend on how many enrolled patients experience tumor size reduction. MGCD265 will be administered orally, twice daily. The study is designed to evaluate whether the number of patients experiencing tumor size reduction is substantially higher than would be expected with other available treatments. (NCT02544633)
Latest
news: * On January 5, 2017, Mirati Therapeutics announced data the Phase 1b and Phase 2 trials of glesatinib, a spectrum selective kinase inhibitor for the treatment of non-small cell lung cancer (NSCLC) patients with genetic alterations of MET. The SDD formulation of glesatinib was introduced into the Phase 1b trial and Phase 2 AMETHYST trial in May of 2016. This formulation has thus far demonstrated improved tolerability versus the prior miglyol soft gel formulation. * On December 21, 2015, Mirati Therapeutics announced that the Phase 2 clinical trial of glesatinib (MGCD265) has commenced. The Phase 2 clinical trial will evaluate glesatinib in NSCLC patients with activating genetic alterations of the MET gene, including MET gene amplification and MET mutations. This study will be conducted at up to 140 clinical trial sites. The purpose is to evaluate the safety and efficacy of glesatinib in NSCLC patients with MET gene alterations, which are known oncogenic drivers. Eligible patients must have failed at least one prior treatment with a platinum-based chemotherapy regimen. The trial will enroll patients with MET gene amplification or MET mutations (including exon-14 deletion mutations). The primary endpoint of the study is Objective Response Rate and the secondary endpoint is Progression Free Survival.
Patients from both Phase 1b and Phase 2 trials were assessed as of December 2, 2016 to evaluate the impact of the new SDD formulation (n=41) as compared to the prior soft gel formulation (n=50). Adverse event-related (AE-related) dose reductions occurred in 17% (7/41) of patients treated with the new SDD formulation, versus 46% (23/50) of patients treated with the prior soft gel formulation. In patients who were transitioned to the SDD formulation during their therapy (n=12), AE-related dose reductions took place in 8% (1/12) of patients versus 33% (4/12) of patients treated with the soft gel formulation.
In an initial evaluation of 24 genetically-selected patients treated with the SDD formulation of glesatinib:
11 patients were in the Phase 2 MET Exon 14 deletion mutation cohort, of whom eight were evaluable.
Eight patients were in the Phase 2 MET amplification cohort, all of whom were evaluable.
Five patients were in the Phase 1b trial with MET Exon 14 deletion mutations, who had clinical characteristics and genetic driver alterations identical to the entry criteria in the ongoing Phase 2 trial, all of whom were evaluable.
In MET Exon 14 deletion patients treated with the SDD formulation across both the Phase 1b and Phase 2 trials, glesatinib demonstrated promising activity:
In the Phase 2 trial, one confirmed partial response (PR) and two unconfirmed PRs out of the eight evaluable patients were observed. One unconfirmed PR remains on study awaiting a confirmatory scan. Tumor reduction was observed in six of eight evaluable patients.
In the Phase 1b trial, three confirmed PRs out of five evaluable patients were observed. Tumor reduction was observed in all five patients.
Overall, data in these 13 patients reflect an objective response rate (ORR) of 46% across the Phase 1b and Phase 2 patient populations, including confirmed and unconfirmed responses. Tumor reduction was observed in 11 of 13 patients.
The longest duration on study is more than 55 weeks and the patient remains on study.
In MET amplification patients treated with the SDD formulation, glesatinib also demonstrated clinical benefit:
In the Phase 2 trial, two unconfirmed PRs out of eight evaluable patients were observed. Neither of the unconfirmed responses remains on study. Tumor reduction was observed in six of eight evaluable patients.
The longest duration on study is more than 24 weeks and the patient remains on study.
Mirati Therapeutics expects to provide an additional update on the glesatinib program in the second half of 2017
