- An interim analysis that sank hopes for Argos Therapeutics Inc.'s rocapuldencel-T earlier this year is now offering additional data which the company says shows the immuno-oncology drug is working as intended.
- The Phase 3 ADAPT trial evaluated a combination of rocapuldencel-T and Pfizer Inc.'s Sutent (sunitinib) versus Sutent monotherapy. Of the 146 patients whose immune responses were assessed by the time of the trial's interim analysis in February, investigators found antigen-specific memory T-cell counts rose only among those who took rocapuldencel-T.
- That result would seem to support Argos' hypothesis that rocapuldencel-T could help trigger an immune response against tumors in patients with renal cell carcinoma. Even so, Argos will need to show more proof to convince investors and regulators the drug actually has a therapeutic benefit.
Though the new data paint a somewhat rosier picture of rocapuldencel-T, Argos still has a great deal of work ahead to regain investor confidence in its drug — and its overall business. Following February's interim analysis wherein an independent data monitoring committee recommended discontinuing ADAPT for futility, the company's stock plummeted more than 63% to $1.60 apiece.
Shares now trade below a quarter per share, signaling low confidence from the market in Argos' ability to rebound.
Despite the committee's recommendation, Argos chose to forge ahead with ADAPT, in part because it "considered the data too immature to observe the delayed effects typically associated with immunotherapy," according to a Nov. 11 statement. During an April meeting with the Food and Drug Administration, the agency ultimately supported Argos' move and agreed to review both a protocol amendment that would extend the trial as well as a revised statistical analysis plan.
Surely weighing on Argos' decision too were the investments already put into ADAPT. Not only did the trial enroll nearly 500 patients with metastatic renal cell carcinoma (mRCC), but it is also the most advanced of Argos' rocapuldencel-T studies. The biotech is testing the drug in other cancers too, including non-small cell lung cancer, but those studies are in Phase 2.
Fortunately for Argos, the new findings from the February interim analysis lend some support for its decision to continue ADAPT.
In the updated analysis, Argos found the average number of antigen-specific memory T-cells roughly doubled from what it was prior to treatment for patients who received at least seven doses of Argos' drug. Investigators also observed a significant correlation between survival and the change in the number of antigen-specific memory T-cells from baseline.
"This was very good to see that we can stratify the survival based on the magnitude of the memory T-cell response, and this is consistent with our observations from the Phase 2 trial and fully in line with our expectations for the mechanism of action," Charles Nicolette, Argos' chief scientific officer, said during a Nov. 13 investor call.
Aside from Rocapuldencel-T therapy's potential to boost antigen-specific memory T-cells, investigators noted that among patients in ADAPT's experimental arm, an association existed between survival and higher than median percentage of regulatory T-cells at baseline.
Interestingly, patients in the control arm demonstrated the opposite when it came to percentage of regulatory T-cells at baseline — higher percentages were associated with poorer survival. Argos said it will need additional time and clinical data in order to understand the scope of those associations.
"When we did the interim analysis that led to the recommendation of not continuing the study, the data were very immature and the data we're looking at here is from that same data cut from February of 2017. So, I think it's too early to tell whether or not the baseline regulatory T-cell levels would be a useful screening tool for inclusion criteria in another protocol," Nicolette said.
Argos expects data from the next planned interim analysis sometime during the first half of 2018 — although the company is still waiting for sign-off from the FDA on a revised protocol for the study that it has yet to submit.