Key Efficacy End Points Upheld at 3 Years for Cemiplimab in CSCC

Danny Rischin, MD

Three-year follow-up data from the phase 2 EMPOWER-CSCC-1 trial (NCT02760498) demonstrated a clinically meaningful survival and duration of response (DOR) improvement with cemiplimab-rwlc (Libtayo) in patients with advanced cutaneous squamous cell carcinoma (CSCC).¹

A poster session at the 2020 American Society of Clinical Oncology Virtual Scientific Program presented by Danny Rischin, MD, highlighted the important aspects of these data, including an overall response rate (ORR) of 46.1%, complete response (CR) rate of 16.1%, and a median time to CR of 11.2 months in 89 responders. The DOR had not yet been reached at the time of data cutoff.

“The data demonstrated deepening clinical responses with cemiplimab over time. Furthermore, duration of response and overall survival [OS] are considerably longer with cemiplimab than what has previously been recorded with other agents,” said Rischin, director of the Division of Cancer Medicine and head of the Department of Medical Oncology at the Peter MacCallum Cancer Centre in Victoria, Australia.

This open-label, non-randomized, multicenter, international study included 3 groups of patients with advanced CSCC. Group 1 contained patients with metastatic disease and group 2 had patients with locally advanced disease; in both groups, patients received 3 mg/kg of cemiplimab every 2 weeks. In group 3, patients with metastatic disease received 350 mg every 3 weeks. The median duration of follow-up was 15.7 months for all 3 groups.

Group 1, 2, and 3 had primary data and follow-up at about 1 year, and group 1 had follow-up again at about 2 years. Of 193 patients total, group 1 had 59 patients, group 2 had 78, and group 3 had 56.

In group 1, there was a CR rate of 6.8% at primary analysis, 16.9% at 1 year, and 20.3% at 2 years. Group 2 had a CR rate of 12.8% in the primary analysis and at 1-year follow up. Group 3 had a 5.4% CR rate at primary analysis and 16.1% rate at 1 year.

The ORR per independent central review was 50.8%, 44.9%, and 42.9% for groups 1, 2, and 3, respectively. For patients who had not received prior anticancer systemic therapy (n = 128), the ORR was 48.4%; for those who did receive prior anticancer systemic therapy (n = 65), it was 41.5%.

For this study, median DOR had not been reached (range, 1.9-34.3 months), nor had the OS. At 24 months, the Kaplan-Meier estimated probability of OS was 73.3% (95% CI, 66.1%-79.2%). There was an estimated proportion of 69.4% of patients with ongoing response at 24 months (95% CI, 55.6%-79.6%).

The estimated median progression-free survival for all patients was 18.4 months (95% CI, 10.3-24.3). The Kaplan-Meier estimated progression-free survival rate was 44.2% at 24 months (95% CI, 36.1%-52.1%).

Overall, there was a 2-month observed time to response in 46.1% of patients, 2 to 4 months for 32.6%, 4 to 6 months for 9.0%, and 6 months or more for 12.4%.

In terms of treatment-emergent adverse events (TEAEs) in the total population, 99.5% of patients experienced at least one any-grade TEAE, regardless of attribution. The most common any-grade TEAEs overall were fatigue at 34.7%, diarrhea at 27.5%, and nausea at 23.8%. There were no new TEAEs leading to death.

Grade 3 or more TEAEs regardless of attribution occurred in 48.7% of patients. The most common were hypertension at 4.7% and anemia and cellulitis at 4.1% each. Treatment-related AEs were reported in 17% of patients, with pneumonitis at 2.6% and autoimmune hepatitis at 1.6% being the most common.

At baseline, patients had a median age of 72 (range, 38-96) and 83.4% were male. All patients had an ECOG performance status of 0 (44.6%) or 1 (55.4%). Cemiplimab was a first-line therapy in 66.3% of the patients.

There was a median duration of exposure to cemiplimab of 51.1 weeks (range, 2.0-109.3) and the median number of doses of cemiplimab administered was 18 (range, 1-48).

The original data of cemiplimab monotherapy, a high-affinity, highly potent human immunoglobulin G4 monoclonal antibody to the PD-1 receptor, had a median follow-up of 9.4 months. This was the basis for the FDA approval in patients with metastatic or locally advanced CSCC.² The regimen achieved clinically meaningful activity in these patients and its safety profile was consistent with other anti-PD-L1 inhibitors.

^REFERENCES

1. ^{Rischin D, Khushalani NI, Schmults CD, et al. Phase II study of cemiplimab in patients (pts) with advanced cutaneous squamous cell carcinoma (CSCC): longer follow-up. J Clin Oncol. 2020;38(suppl 15):10018. doi:10.1200/JCO.2020.38.15_suppl.10018}
2. ^{FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. Updated January 18, 2019. Accessed May 30, 2020. https://bit.ly/36KDJhv}