When used with cemiplimab, an anti-PD-1 agent, ISA101b (peltopepimut-S), a therapeutic vaccination against the HPV-specific E6/E7 oncoproteins, causes a particular proliferation of T cells that are specifically targeted by HPV16. In studies for patients with recurrent/metastatic (R/M) HPV16+ oropharyngeal cancer, the study demonstrated that ISA101 in combination with nivolumab led to a greater response rate than an immune checkpoint inhibitor (ICI) alone.
The US FDA granted fast-track designation to ISA101b for the treatment of recurrent and metastatic HPV16-positive OPC.
ISA Pharmaceuticals initiated an open-label study of Cemiplimab and ISA101b vaccine in patients with recurrent/metastatic HPV16 positive oropharyngeal cancer who have experienced disease progression with prior anti-PD-1 therapy. The primary outcome of the study was to assess the objective response rate (ORR) based on radiographic response.
According to the results presented at ASCO 2023, twenty-six patients were included in Stage 1 with a mean age of 60.7 ±12.9 years, 22 (84.6%) male, and 4 (15.4%) female. The range of the median follow-up was 16.2 weeks (1.6–78.8). Two of the three patients with partial response never reacted to prior ICI therapy; three patients were found to have a partial response (PR) (11.5%). The best overall response (BOR) was stable disease (SD) in 13 patients (50.0%) and PD in eight individuals (30.8%). Two patients (7.7%) did not get a tumor assessment after baseline: one patient died on day 8 from OPC, and the other withdrew permission soon after enrolling. A clinical benefit ratio of 61.5% was recorded. Nine patients (34.6%) received a booster shot. Two patients had PR at the time of the booster, while five patients had substantial (6 months) results.
Erythema at the injection site and diarrhea are two Grade III adverse events (AEs) that were reported in relation to ISA101b. Grade III ICI-related auto-immune reactions occurred in two individuals (7.7%). AEs in grades 4-5 unrelated to the study's therapy did not occur and the median overall survival was 8.1 months.
“It seems that the targeted therapeutic cancer vaccine ISA101b in combination with an anti-PD1 antibody can have a real stabilizing effect in a good portion of patients as the disease control rate (DCR) at 6 months is the most striking feature of the data set of anti-PD1 therapy-resistant head and neck cancer patients.” -Expert Opinion.
The combination of ISA101b and cemiplimab in patients had an overall response rate (ORR) of 15.4%. In 26.9% of all patients, long-term (6 months) disease stabilization was accomplished. The safety profile of the cemiplimab and ISA101b combination was similar to that of anti-PD-1 monotherapy and was well tolerated