Bechter, Oliver

Abstract Background: Cemiplimab is the first treatment approved in the US (as cemiplimab-rwlc) for patients with metastatic basal cell carcinoma (mBCC) or locally advanced disease (laBCC) after hedgehog inhibitor (HHI) treatment or for whom an HHI is not appropriate. Cemiplimab provided substantial clinical benefit and an acceptable safety profile in patients with laBCC who discontinued HHI therapy due to progressive disease (PD), intolerance, or no better than stable disease (SD) after 9 months (NCT03132636). Here, we present the primary analysis of the mBCC cohort. Methods: Patients with mBCC (nodal or distant) post-HHI treatment received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until PD. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Key secondary endpoints included safety and tolerability, ORR per investigator (INV) assessment, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and complete response (CR) rate (data cutoff date: May 20, 2021). Results: Fifty-four patients were enrolled (70.4% male; median age 63.5 years [range, 38−90]; Eastern Cooperative Oncology Group performance status 0 [66.7%] and 1 [33.3%]). Median duration of follow-up was 8.4 months (range 1.5-36.2). ORR per ICR was 24.1% (95% confidence interval [CI], 13.5-37.6); with 1 CR and 12 partial responses (PRs). ORR per INV was 25.9% (95% CI, 15.0-39.7), with 2 CRs and 12 PRs. Among responders, median time to response per ICR was 4.0 months (range, 2.0−10.5). Estimated median DOR per ICR was 16.7 months (95% CI, 9.8-not evaluable). Disease control rate was 63.0% (95% CI, 48.7-75.7) per ICR and 70.4% (95% CI, 56.4-82.0) per INV. Median OS was not reached. Median PFS per ICR was 8.3 months (95% CI, 4.2-15.9). The most common treatment-related adverse events were fatigue (37.0%), diarrhea (14.8%), pruritus (13.0%), hyperthyroidism (9.3%), and arthralgia (9.3%) as well as hypothyroidism, asthenia, constipation, and maculo-papular rash (7.4% each). There were no treatment-related deaths. Conclusions: Cemiplimab provided clinically meaningful antitumor activity, including durable responses, and an acceptable safety profile in patients with mBCC who had progressed on or were intolerant to HHI therapy. Citation Format: Karl Lewis, Ketty Peris, Aleksander Sekulic, Alexander J. Stratigos, Lara Dunn, Zeynep Eroglu, Anne Lynn S. Chang, Michael R. Migden, Suk-Young Yoo, Kosalai Mohan, Ebony Coates, Emmanuel Okoye, Timothy Bowler, Jean-François Baurain, Oliver Bechter, Axel Hauschild, Marcus O. Butler, Leonel Hernandez-Aya, Lisa Licitra, Rogerio I. Neves, Emily S. Ruiz, Frank Seebach, David M. Weinreich, George D. Yancopoulos, Israel Lowy, Priscila Goncalves, Matthew G. Fury. Primary analysis of phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT165.

9566 Background: Cemiplimab-rwlc is the first immunotherapy to receive approval in the US, fully for pts with laBCC and accelerated for metastatic BCC, post hedgehog inhibitors or for whom hedgehog inhibitors are not appropriate. Cemiplimab resulted in clinically meaningful anti-tumor activity in pts with laBCC who progressed on or were intolerant to hedgehog inhibitor therapy (NCT03132636). This analysis evaluated HRQoL in these pts. Methods: Adults with laBCC and ECOG performance status ≤1 (n=84) received IV cemiplimab 350 mg Q3W for up to 9 treatment cycles. At baseline (BL) and day 1 of each cycle (C), pts completed EORTC QLQ-C30 and SKINDEX-16 questionnaires that assess Global Health Status (GHS)/QoL, functioning, and BCC-related symptoms. Mixed-effects repeated measures (MMRM) models were used to estimate least squares (LS) mean (standard error [SE]) change from BL during treatment (i.e., across C2 to C9); changes ≥|10| points were considered clinically meaningful. Responder analyses were conducted in pts with non-missing data from BL to determine the proportions with clinically meaningful improvement or deterioration, or stability on QLQ-C30 and SKINDEX-16 at C2 and C9; a 10-point threshold was considered meaningful for both instruments. Results: BL scores showed moderate to high levels of functioning and low symptom burden. In MMRM models, overall changes from BL on QLQ-C30 indicated stability for GHS/QoL and all scales except for clinically meaningful worsening of fatigue (LS mean [SE] change 12.5 [3.9]; P<.05). In responder analysis, the majority of pts reported clinically meaningful improvement or stability at C2 and C9 on all QLQ-C30 functioning scales and the key symptom of pain but not fatigue (Table). On SKINDEX-16, MMRM models showed clinically meaningful improvement on the emotional subscale (LS mean [SE] change –13.2 [3.9]; P<.05) and stability on the symptom and functional subscales. Responder analysis showed clinically meaningful improvements or stability across the SKINDEX-16 subscales in approximately 80% of pts at C2, and 70–80% of pts at C9. Conclusions: In laBCC pts treated with cemiplimab, the majority reported clinically meaningful improvement or stability in GHS/QoL and functional status while maintaining a low symptom burden except for fatigue. Clinical trial information: NCT03132636. [Table: see text]