Hello Chickpea,
Hereby the article of A.F. on STAT News. He's quite negative about ONCS. 24% ORR isn’t impressive enough in his opinion. He’s skeptical about the regulator pathway ONCS is following. He doesn’t believe it could be approved by the FDA in the current setting.
I agree that a double arm study ( Pembro alone vs Pembro + TAVO ) would be more effective to prove the efficacy of TAVO.
But I don’t agree with his statement about Idera. It’s always difficult to compare studies, especially in combo-setting but I point out : inclusion criteria, duration of response, AE are in favor of TAVO and DCR is better with Idera.
Notice also that TAVO + Pembro need some time to become effective ( typically after 3 or 6 months ) and the numbers are still limited.
The ORR of Idera is 32% or 29,4% ( 10/34 and 2 CR) if you apply RECIST V1.1 vs 24% ( 5/21 and 1 CR ) with TAVO + Pembro.
What do you think?
OncoSec Medical announced updated but mixed results from a clinical trial treating skin cancer patients with a combination of its experimental immunotherapy drug, called Tavo, plus Merck’s checkpoint inhibitor Keytruda.
The good news: The efficacy of the Tavo-Keytruda combination improved with more skin cancer patients treated and longer follow-up, compared to initial results shown last fall. The bad news: Even with an overall response rate now at 24 percent, the refreshed Tavo-Keytruda data still don’t make a convincing case to develop this combination approach any further.
Unbowed, OncoSec is pushing ahead and sees a path toward a marketing submission to the Food and Drug Administration. I’m skeptical, and judging by the downtick in the biotech’s stock price since the data reveal on Feb. 1, so are a lot of investors.
As a reminder: Injecting skin cancer lesions with Tavo is meant to overcome immune resistance that prevents about two-thirds of skin cancer patients from responding to checkpoint inhibitors like Keytruda, when used alone. Skin cancer patients are eligible for enrollment into the OncoSec clinical trial, known as Keynote-695, only if they have confirmed, refractory disease — meaning their tumors were growing despite prior treatment with checkpoint inhibitors.
Last November, OncoSec treated nine patients with Tavo-Keytruda, eliciting two unconfirmed partial responses. The result was hard to interpret, at best, but mostly disappointing.
In the update, 21 skin cancer patients have now been treated with Tavo-Keytruda, with a single complete response and four partial responses. That’s an overall response rate of 24 percent. All of the responses are ongoing, with durations ranging from six to near nine months.
Without a control arm in the study for comparison, making a judgment about the clinical relevance of a 24 percent response rate for Tavo-Keytruda is difficult. As I’ve mentioned before, other biotechs working on similar “add-on” immunotherapies to checkpoint inhibitors in skin cancer have shown response rates in the range of 18 percent to 38 percent.
For example, an immune-boosting drug from Idera Pharmaceuticals added to the CTLA-4 inhibitor ipilimumab (Bristol’s Yervoy) yielded an overall response rate of 32 percent in a mid-stage study.
OncoSec believes an overall response rate of 20 percent or more is clinically meaningful for the type of skin cancer patients it’s targeting with Tavo-Keytruda, mainly because these patients don’t have any approved treatment options. The company plans to to enroll up to 100 patients in the Keynote-695 study into the second half of the year. If the overall response rate stays above 20 percent with a median duration of response of six months or more, OncoSec will file for accelerated approval with the FDA in early 2020.
This plan is risky. The FDA has not specifically told OncoSec that a 20 percent response rate is good enough for approval in this situation. “Approvability will be a review issue,” OncoSec told me, adding that they’d expect the FDA to bring the drug in front of an advisory committee.
The FDA could also refuse to accept an accelerated review filing. It’s noteworthy that Idera, also pursuing its own combination immunotherapy in skin cancer, as I mentioned above, has decided to conduct a randomized Phase 3 study with overall survival as the primary endpoint.
