Abstract CT006: Phase 2 study of pembrolizumab (pembro) for locally advanced (LA) or recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC): KEYNOTE-629

Abstract

Background: In the multicenter, open-label, nonrandomized, phase 2 KEYNOTE-629 trial, pembro has demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile for R/M cSCC based on the first interim analysis (IA). Here, we present the second IA of KEYNOTE-629, which reports the initial efficacy and safety data for the LA cohort and updated data for the R/M cohort in cSCC.Methods: Eligible patients (pts) were ≥18 years old, had histologically confirmed cSCC (LA or R/M) with measurable disease per RECIST 1.1 by blinded independent central review (BICR), an ECOG PS score of 0 or 1, and adequate organ function. Pts received intravenous pembro 200 mg every 3 weeks for up to 35 infusions (~ 2 years) or until protocol-specified treatment discontinuation criteria were met. The primary endpoint was ORR per RECIST 1.1 by BICR. Secondary endpoints were DOR, DCR, and PFS, all per RECIST 1.1 by BICR; OS; and safety and tolerability. Results: A total of 159 pts were enrolled and treated with pembro (LA, n=54; R/M, n=105). The median time from the first dose to data cutoff (July 29, 2020) was 14.9 (range, 10.1-19.4) mo for the LA cohort and 27.2 (range, 24.6-32.0) mo for the R/M cohort. In the LA cohort, 22.2% of pts were treated with prior systemic therapy with curative intent. In the R/M cohort, 86.7% of pts received ≥1 prior systemic therapy. Updated efficacy outcomes are summarized in the table. Across cohorts, grade 3-5 treatment-related AEs occurred in 11.9% of pts. Grade 3-5 immune-related AEs occurred in 8.2% of pts. Conclusions: Pembro confirmed robust and durable antitumor activity, with promising survival in LA and R/M cSCC. AEs with pembro in this study were generally consistent with its established safety profile. These data support the use of pembro for cSCC. LA cSCC(N=54)R/M cSCC(N=105)Total(N=159)ORR, % (95% CI)50.0 (36.1-63.9)35.2 (26.2-45.2)40.3 (32.6-48.3)DCR (SD ≥12 wks + ORR), % (95% CI)64.8 (50.6-77.3)52.4 (42.4-62.2)56.6 (48.5-64.4)Best overall response, n (%)CR9 (16.7)11 (10.5)20 (12.6)PR18 (33.3)26 (24.8)44 (27.7)SD13 (24.1)30 (28.6)43 (27.0)SD≥12 wks8 (14.8)18 (17.1)26 (16.4)PD9 (16.7)28 (26.7)37 (23.3)NE1 (1.9)2 (1.9)3 (1.9)No assessment4 (7.4)8 (7.6)12 (7.5)DOR, median (range), moNR (1.0+-17.2+)NR (2.7-30.4+)NR (1.0+-30.4+)Patients with extended responses≥12 months, n (%)10 (84.1)25 (77.8)35 (80.3)PFS, median (95% CI), moNR (5.5-NR)5.7 (3.1-8.5)7.8 (5.3-12.3)12-mo PFS rate, % (95% CI)54.4 (39.6-67.0)36.4 (27.0- 45.9)42.4 (34.3-50.2)OS, median (95% CI), moNR (NR-NR)23.8 (13.4-29.8)26.4 (19.5-NR)12-mo OS rate, % (95% CI)73.6 (59.5-83.4)61.0 (50.9-69.5)65.1 (57.1-72.0) Citation Format: Brett G.M. Hughes, Eva Munoz-Couselo, Laurent Mortier, Åse Bratland, Ralf Gutzmer, Osama Roshdy, Rene González Mendoza, Jacob Schachter, Ana Arance, Florent Grange, Nicolas Meyer, Abhishek Joshi, Salem Billan, Pingye Zhang, Burak Gumuscu, Ramona F. Swaby, Jean-Jacques Grob. Phase 2 study of pembrolizumab (pembro) for locally advanced (LA) or recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC): KEYNOTE-629 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT006.

Advances in Cutaneous Squamous Cell Carcinoma Management

“…Hughes et al subsequently analyzed the KEYNOTE-629 trial (summarized in Table 5 ) at a mean follow-up of 27.2 months and a new cohort of 54 patients with locally advanced cSCC treated with pembrolizumab at a mean follow-up of 14.9 months [ 94 ]. The ORR increased slightly to 35.2% in the recurrent and metastatic cohort, and the locally advanced cohort had an ORR of 50.0%.…”

“…The ORR increased slightly to 35.2% in the recurrent and metastatic cohort, and the locally advanced cohort had an ORR of 50.0%. Of note, efficacy comparisons across trials are difficult to interpret, particularly because locally advanced cSCC in the KEYNOTE-629 clinical trial did not include recurrent disease, while locally advanced cSCC in the cemiplimab trials included recurrent disease [ 93 , 94 ]. Eleven percent of patients experienced grade 3 to 5 treatment related adverse reactions, and 8% of patients had grade 3 to 5 immune related adverse reactions [ 94 ].…”

“…Of note, efficacy comparisons across trials are difficult to interpret, particularly because locally advanced cSCC in the KEYNOTE-629 clinical trial did not include recurrent disease, while locally advanced cSCC in the cemiplimab trials included recurrent disease [ 93 , 94 ]. Eleven percent of patients experienced grade 3 to 5 treatment related adverse reactions, and 8% of patients had grade 3 to 5 immune related adverse reactions [ 94 ]. Overall, a durable response and robust anti-tumor response were observed in both cohorts with an acceptable safety profile.…”

Das kutane Plattenepithelkarzinom – ein Update

“…Die offene Phase-II-Studie zur Behandlung des fortgeschrittenen PEK untersucht die Wirksamkeit von Pembrolizumab in einer Dosis von 200 mg alle 3 Wochen. Eine zweite Zwischenanalyse zeigte, dass auch nach 35 Zyklen Monotherapie Pembrolizumab in beiden Gruppen ein andauerndes Ansprechen sowie ein vielversprechendes Überleben erreicht werden konnte (laPEK: ORR 50 %, DCR 64,8 %, PFS 54 %, OS 73,6 %; mPEK: ORR 35,2 %, DCR 52,4 %, PFS 36,4 %, OS 61 %) [38]. Das mediane progressionsfreie Überleben und die Gesamtüberlebenszeit waren beim laPEK noch nicht erreicht und betrugen beim mPEK 5,7 bzw.…”

“…Das mediane progressionsfreie Überleben und die Gesamtüberlebenszeit waren beim laPEK noch nicht erreicht und betrugen beim mPEK 5,7 bzw. 23,8 Monate bei guter Verträglichkeit [38]. Auch die Phase-II-CAR SKIN-Studie (NCT02883556) zeigte bei Patienten mit mPEK und laPEK unter Therapie mit Pembrolizumab vergleichbare Resultate und Nebenwirkungen [39].…”