KEY TAKEAWAYS
- This phase II trial investigated the combination of the anti-PD1 antibody cemiplimab and HHI sonidegib in patients with advanced BCC.
- The study’s primary endpoint was to assess the best response within the first 26 weeks using immune-related criteria. Secondary objectives included 26-week responses, safety, and immunologic changes in biopsy-assessable tumors.
- The study suggested that the anti-PD1 antibody combined with pulsed HHI is well-tolerated and shows promise, but longer follow-up is needed.
The phase II clinical trial enrolled patients (pts) with advanced basal cell carcinoma (BCC), for whom hedgehog pathway inhibitors (HHI) monotherapy is unlikely to provide benefit. The trial began with a two-week administration of sonidegib, followed by cemiplimab every three weeks (q3w) and pulsed dosing of sonidegib (2 weeks on, 2 weeks off) for a maximum of 26 weeks.
The primary endpoint was the best response observed between the initiation of treatment and the 26-week mark, as assessed by immune-related response criteria. Secondary endpoints included response assessment at 26 weeks, safety, and immunological changes in biopsy-assessable tumors.
To date, twelve pts have been enrolled in the trial. The average age is 74 years (range: 57-88 years)—six pts presented with multiple BCCs, three with metastatic BCC, and three with locally advanced BCC. Nine pts had previously experienced skin cancer, whereas three pts with locally advanced BCC had no prior history of skin cancer. Three pts concurrently had hematologic malignancies. Ten pts completed the trial, one is still undergoing treatment, and one patient died during the run-in phase due to a cause unrelated to the treatment.
Notably, one patient achieved a complete response (CR), six demonstrated partial responses (PR), and three exhibited stable disease (SD). All pts experienced treatment-related adverse events (trAEs), with the most common being muscle cramps (9/12 pts), an increase in creatine phosphokinase (CPK) levels (7/12 pts), fatigue (4/12 pts), lichenoid dermatitis (4/12 pts), diarrhea (4/12 pts), pruritus (3/12 pts), and dysgeusia (3/12 pts). Approximately 3.4% of trAEs were of grade 3-4 severity.
The study demonstrated that the combination of anti-PD1 antibody and pulsed HHI is well-tolerated among pts with multiple comorbidities and exhibits promising efficacy signals. However, longer-term follow-up is necessary.
Source: https://eado2023.com/wp-content/uploads/2023/04/Abstract-Band_EADO2023_Stand-21-04-2023-kl.pdf
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04679480
Ramelyte, E., Prieto, N.M.R., Pawlik, L., Boerlin, A., Maul, J-T., Naegeli, M.C., Staeger, R., Dummer, R. Anti-PD1 antibody cemiplimab combined with pulsed hedgehog inhibitor sonidegib in advanced basal cell carcinoma.
