Replimune’s RP1 is an “active agent” according to CEO Philip Astley-Sparke, but it didn’t achieve the primary endpoints of complete response or overall response in a phase 2 trial of patients with a type of skin cancer.
The biotech’s shares halved as the markets opened Tuesday, from $11.95 at open to $6.13. Despite the bleak update for the cutaneous squamous cell carcinoma (CSCC) trial called CERPASS, in a broad clinical update Tuesday, Replimune pointed to success in a separate melanoma study that could lead to a regulatory filing.
On the CSCC front, RP1 was being tested in 211 patients with locally advanced or metastatic CSCC, randomized to receive either RP1 plus Regeneron’s Libtayo or Libtayo standard of care. The trial did not meet either primary endpoints assessing the complete response rate or overall response rate.
The combo achieved a complete response rate of 38.1% compared to 25% for the standard-of-care group, which was just shy of the threshold for statistical significance. The p-value was 0.025. Replimune singled out patients with locally advanced disease, who had a slightly higher response rate of 48.1% for the RP1 group compared to 22.6% for standard of care. The overall response rate was comparable in the two groups, at 52.5% and 51.4%, respectively.
Replimune also flagged that the RP1 group seemed to have a higher duration of response compared to Libtayo alone, but the data is not yet mature and needs further follow-up.
“Of note, RP1 plus cemiplimab provided particularly meaningful clinical activity for many patients with difficult-to-treat, disfiguring tumors that typically have the greatest impact on quality of life, given their size and location,” the company said.
Replimune blamed an imbalance in baseline tumor burden in the treatment groups, which may have impacted the responses. A greater number of patients who had larger tumors, measured at 10 cm or more, ended up in the RP1 group, the company said.
The trial will go on to assess the duration of response, progression-free survival and overall survival.
On safety, Replimune reported mostly grade 1 and 2 flu-like symptoms, “a range” of grade 3 events in one patient in each group and one grade 4 instance of immune-mediated myocarditis and myocarditis in each arm of the trial. There were no deaths reported.
Replimune also unveiled initial data from a group of patients with anti-PD1 failed melanoma from the phase 1/2 program called IGNYTE. The therapy was tested in 140 patients for this registrational cohort, but Replimune also presented data today on a group of 16 patients from an earlier cohort in the indication.
Patients taking RP1 and Bristol Myers Squibb’s Opdivo had an overall response rate of 31.4% and a complete response rate of 12%, which is consistent with a prior “snapshot” of 91 patients from the trial, Replimune said. About half of the patients experienced clinical benefit: either complete response, partial response or stable disease. All of the patients have ongoing responses at six months, and 78% have responses ongoing as of Nov. 6. Replimune expects a primary analysis from the study once all patients achieve 12 months of treatment, which should occur around March 2024.
Again, Replimune reported primarily grade 1 and 2 treatment-related adverse events, with flu-like symptoms the most common. The company said there was “a low incidence of Grade 3-5 events”—a grade 5 meaning a patient death. There were four grade 4s reported, which signifies a life-threatening condition or one requiring urgent intervention. Replimune said there was a case each of increased lipase, cytokine release syndrome, myocarditis and hepatic cytosis.
The death was a case of myocarditis that Replimune said was attributed to Opdivo, for which it is a known complication.
Replimune recently met with the FDA for a type C meeting, where the company got the agency’s blessing for the design of a confirmatory study in anti-PD1 failed melanoma. Replimune will conduct a two-arm randomized trial with a physician’s choice treatment as a comparator. The phase 3 trial should be underway by the time the company submits an application for accelerated approval in this population. A full biologics license application should be submitted once the patients have been followed for 12 months, around the second half of 2024.
With all this going on, Replimune has decided to trim its pipeline to focus on the confirmatory trial for anti-PD1 failed melanoma and a registrational study for RP2 in uveal melanoma. Development of RP2 and RP3 in squamous cell carcinoma of the head and neck and colorectal cancer will be discontinued, Replimune said. RP2 will continue in second-line hepatocellular carcinoma, while RP3 will be discontinued entirely.
Replimune has $496.8 million in cash on hand as of Sept. 30, which should last the company into early 2026.