OncoSec Medical’s six-year pursuit of potentially pivotal data on its Keytruda combination has delivered a last-minute twist. After touting an 18.8% investigator-assessed response rate, the biotech has revealed that the final result per blinded independent central review (BICR) fell well short of the bar for success.
The phase 2b clinical trial tested OncoSec’s interleukin 12 (IL-12) encoding plasmid in combination with Merck & Co.’s Keytruda in patients with unresectable or metastatic melanoma who had progressed after treatment with an anti-PD-1 checkpoint inhibitor. OncoSec needed to link the combination to at least a 17% overall response rate (ORR) to hail the single-arm study as a success.
In November, the biotech offered evidence that it was on track to meet that objective, reporting that the investigator assessment put the ORR at 18.8%. If BICR, the form of assessment for the primary endpoint, replicated the finding, OncoSec could claim the study as a success.
Instead, the ORR in the blinded review clocked in at 10.2%. The gap between the two results stemmed from different interpretations of the number of partial responses. Blinded assessors actually reported more complete responses, four versus three, but that difference was more than offset by them finding 10 fewer partial responses.
Sponsors use BICRs to independently verify their endpoints and control for bias. In BICRs, radiologists and oncologists who are blinded to investigator assessments review images of treated and non-treated lesions. Unfortunately for OncoSec, the blinded review delivered a very different result from investigator assessment.
Not that OncoSec is letting the failure on the primary endpoint dent its enthusiasm for the program. Instead, the biotech pointed to the median overall survival (OS) of 22.7 months and data from an investigator-sponsored trial in neoadjuvant melanoma to make the case for further development.
OncoSec plans to meet with the FDA next month with a view to starting a randomized phase 2 clinical trial in the second half of the year. While single-arm studies were in fashion when OncoSec started its last trial in 2017, the FDA now wants sponsors to run randomized trials to win even accelerated approval, reflecting a raft of issues including worries that data such as the 22.7-month median OS can be “uninterpretable.”
Funding could be a barrier to OncoSec’s desire to take the IL-12 candidate into another study. The biotech ended January with $3.7 million, a sum it forecast would keep it going into the second quarter. A stock offering could extend the cash runway, but, with its share price falling over 50% to $1.27 in the wake of the phase 2 data, OncoSec is raising from a position of weakness. The biotech’s market cap is $3.8 million.