Spectrum Pharmaceutecals Inc (SPPI)

[antihama]

Will MDAs basket trial be a multi-site trial or will it be one site of a multi-site SPPI trial? Previously, I was wondering if a multi-site trial is necessary for approval.

Hopefully MDA will be leading a multi-site trial which I believe is a necessity (but don’t know for sure) for approval since it stands to reason that MDAs NSCLC trial would have fulfilled the requirement for approval but Spectrum went ahead and started a multi-site trial.

I believe MDAs pozi 50 pt NSCLC EGFR cohort was not pivotal because it wasn't a multi-site trial and hence SPPI needed to run a multi-site trial. FDA comfort level may be a little low because these unmet need trials are not randomized or placebo controlled so I'm assuming they at least want to have it multi-site to get it to be somewhat Adequate and well-controlled (AWC). A 50 patient trial is not a problem either. Xaltori to treat the ROS1 NSCLC mutation with only a 50 pt cohort but it was multi-site (and international) and it got AA. Not only that but it started out as a dose finding study! So I got to assume that since MDAs NSCLC trial had enough patients (i.e. 50 is greater than 33) they initiated SPPIs HSCLC trial to get a multi-site requirement. Just speculating but seems reasonable. Here’s more info on the ROS1 AA trial design

PROFILE 1001 was a single-arm, multicohort, multicenter, international trial [42, 48]. The trial was initially a dose-finding study, with the protocol later being amended to include specific molecularly defined cohorts. In addition to the ROS1 NSCLC cohort that was initiated in November 2009, the trial included an ALK-positive NSCLC cohort (results of which supported the initial accelerated approval crizotinib), an ALK-negative NSCLC cohort, a c-MET-amplified NSCLC cohort, and an enriched other-cancer ALK-, ROS1-, c-MET-positive cohort. A total of 30 patients were initially planned to be enrolled into the ROS1-positive NSCLC cohort, which was later increased to a total of 50 patients to provide a more accurate estimation of efficacy in this patient population. The ROS1-positive cohort consisted of patients with mNSCLC whose tumors were prospectively determined to have ROS1 genetic rearrangements. Patients with mNSCLC were eligible irrespective of receipt of prior lines of therapy. Other key criteria included having an Eastern Cooperative Oncology Group performance status of 0, 1, or 2, measurable disease, adequate organ function, and no prior treatment with an ALK or c-MET inhibitor. Patients received crizotinib 250 mg by mouth twice daily until disease progression or intolerable drug toxicity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978556/#B38