TIL (today I learned) that now is not the time to disappoint investors. Iovance Biotherapeutics trumpeted a 29% response rate and a 10.4-month median duration of response in a pivotal advanced melanoma trial of its tumor-infiltrating lymphocyte (TIL) candidate—and saw its stock plummet almost 50% on an unfavorable comparison to earlier data.
Last summer, Iovance set the bar for its TIL candidate lifileucel by posting data on the second cohort of its phase 2 trial. In the 66-subject cohort, the biotech saw three complete responses and 21 partial responses, giving it an objective response rate of 36%. After a median of 33.1 months of follow-up, the study was yet to hit its median duration of response. The cohort is still yet to reach the median duration of response after 36.6 months.
California-based Iovance shared data from the 87-subject pivotal fourth cohort of the clinical trial late on Thursday. The objective response rate came in at 29%, reflecting the three complete responders and 22 partial responders. After a median follow-up of 23.5 months, the median duration of response was 10.4 months.
Iovance compared the data favorably to standard of care. Participants in the clinical trial had advanced melanoma and had previously tried at least one systemic therapy including a PD-1/L1 antibody and, if appropriate, BRAF or BRAF/MEK inhibitor therapy.
“The expected durability of responses with the available therapy, which is monotherapy chemo, sometimes doublet chemo, is as low as 3.5 months. So 10.4 months is definitely meaningful,” Friedrich Graf Finckenstein, chief medical officer at Iovance, said on a conference call with analysts to discuss the data. Finckenstein said chemotherapy has a 4% to 10% response rate in the targeted population.
However, investors compared the data unfavorably to the second cohort. Shares in Iovance fell around 50% in after-hours trading, sinking the stock to below $8 and wiping more than $1 billion off the market cap of the biotech.
Iovance addressed the differences between the cohort two and four data on the conference call. As Iovance sees things, the data reflect differences between the baseline characteristics of participants in the two cohorts.
“Patients in cohort four had higher baseline disease burden in comparison to patients in cohort two. This finding was supported by a higher proportion of cohort four patients with elevated baseline lactate dehydrogenase or LDH levels, which is a well known negative prognostic factor in melanoma. Patients in cohort four also had a greater number of IRC-identified tumor lesions at baseline,” Finckenstein said.
The two cohorts had the same inclusion/exclusion criteria. Finckenstein said investigators may be “a little more conservative” when first enrolling a trial, before opening up to a broader patient population once they see efficacy data. “I'm not surprised that that changes over time, and that we might be seeing some patients who have worse prognostic factors being enrolled,” Finckenstein said.
While investors are spooked, Iovance is pushing ahead with regulatory plans, setting its sights on submitting data from the second and fourth cohorts to the FDA in a biologics license application in August. One analyst brought up financing as another concern but, with more than $500 million in cash, Iovance’s C-suite is OK with the situation and isn’t actively looking for more funding.