Trial Success Criteria

*****Reposted as the other thread has turned to a discussion about management*****

Trying to determine the level of benefit that PAT-SM6 must contribute to this trial to be considered a success and for Onyx to seek an agreement.

From the announcement it appears we need a partial response in at least 33% of patients to continue on to the next stage of the trial. Let's assume this is the baseline to be considered a success.

We then need to estimate what Kyprolis and dexamethasone would be expected to achieve without combination with PAT-SM6 for patients who are "refactory and/or intolerant to bortezomib" (PAB Trial Annoucment). I am not sure whether bortezomib is the first treatment given and therefore the trial would be the second treatment or if there are prerequisite treatments before bortezomib is given. The closest I can find is:

"On July 20, 2012, the Food and Drug Administration (FDA) granted accelerated approval to carfilzomib injection (Kyprolis™, made by Onyx Pharmaceuticals), for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of the completion of the last therapy.
The approval was based on the results of a single-arm, multicenter clinical trial enrolling 266 patients with relapsed multiple myeloma who had received at least two prior therapies, including bortezomib and an immunomodulatory agent (thalidomide or lenalidomide). Carfilzomib was administered intravenously over 2 to 10 minutes on 2 consecutive days weekly for 3 weeks, followed by a 12-day rest period (28 day treatment cycle). Treatment was continued until disease progression, unacceptable toxicity, or completion of a maximum of 12 cycles. Patients received 20 mg/m2 at each dose in cycle 1, and 27 mg/m2 in subsequent cycles.
...
"The primary efficacy endpoint was overall response rate (ORR), determined by Independent Review Committee assessment using International Myeloma Working Group criteria. The ORR was 22.9 percent (95 percent CI: 18.0, 28.5), consisting of 1 complete response, 13 very good partial responses, and 47 partial responses. The median response duration was 7.8 months (95 percent CI: 5.6, 9.2)."

(http://www.cancer.gov/cancertopics/druginfo/fda-carfilzomib) - please put forward any better example trials with response rates quoted, this was the best I could find.

The ORR was nearly 23% so from that you would assume that out of nine patients that 2 would have a partial response or better with Kyrpolis alone.

The only trial results available for PAT-SM6 were treating patients with an average of five prior treatments. The OPR for that trial was 0%. We also have the single example of a patient treated in combination with a successful response.

I am a little worried about the small number of patients in the initial trial but I suppose it could skew the results in either direction.