HERCULES - PENIS - IMUNOTERAPIA - ESTUDO BRASILEIRO - MALUF

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5009 Rapid Oral Abstract Session
A phase II trial of pembrolizumab plus platinum-based chemotherapy as first-line
systemic therapy in advanced penile cancer: HERCULES (LACOG 0218) trial.
Fernando Cotait Maluf, Karine Trindade, Daniel D Almeida Preto, Fernando Sabino Marques Monteiro, Murilo Luz, Patricia Milhomem Beato, Diogo Assed Bastos,
Joao Paulo Holanda Soares, Victor Marcondes Lopes dos Santos, Luis Eduardo Werneck De Carvalho, David Queiroz Borges Muniz, Douglas Racy, Susan Halabi,
Taiane Francieli Rebelatto, Gustavo Werutsky, Rafaela Gomes de Jesus, Andre P. Fay; Hospital Beneficência Portuguesa de S~ao Paulo and Hospital Israelita Albert
Einstein; LACOG (Latin American Cooperative Oncology Group), S~ao Paulo, Brazil; LACOG (Latin American Cooperative Oncology Group), Porto Alegre, Brazil; Barretos
Cancer Hospital, Barretos, Brazil; Hospital Universitário de Brası́lia, Universidade de Brası́lia, and Hospital Sı́rio-Libanês; LACOG (Latin American Cooperative Oncology
Group), Brası́lia, Brazil; Hospital Erasto Gaertner, Curitiba, Brazil; Fundaç~ao Amaral Carvalho, Jaú, Brazil; Hospital Sı́rio-Libanês; LACOG (Latin American Cooperative
Oncology Group), S~ao Paulo, Brazil; Hospital Haroldo Juaçaba, Instituto do Câncer do Ceará, Fortaleza, Brazil; Instituto Nacional do Câncer (INCA), Rio De Janeiro, Brazil;
Oncológica do Brasil, Belém, Brazil; Instituto do Câncer do Estado de S~ao Paulo (ICESP), S~ao Paulo, Brazil; BP - Beneficência Portuguesa de S~ao Paulo, S~ao Paulo, Brazil;
Duke University School of Medicine, Durham, NC; PUCRS School of Medicine and Hospital Nora Teixeira; LACOG (Latin American Cooperative Oncology Group), Porto
Alegre, Brazil
Background:Over the last six decades, platinum-based chemotherapy has been the standard of
care first-line treatment for advanced penile squamous cell carcinoma (PSCC). Advanced PSCC
has poor prognosis with limited treatment options. Immune checkpoint inhibitors (ICI) have
been associated with improved efficacy in different types of malignancies, however the benefit
in PSCC is uncertain. Methods: LACOG 0218 (NCT04224740) is a phase II single arm trial
evaluating pembrolizumab plus platinum-based chemotherapy as first-line treatment in
advanced PSCC. Patients (pts) with metastatic or locally advanced disease (recurrent or
TanyN3M0 or T4NanyM0) not amenable to curative-intent therapy received: 5-FU 1000mg/
m²/day IV D1-D4; cisplatin 70mg/m² (or carboplatin AUC 5) IV D1; and pembrolizumab 200mg
IV D1 every 3 weeks (Q3W) for 6 cycles, followed by pembrolizumab 200mg IV Q3W up to 34
cycles. Theprimary endpoint is confirmed overall response rate (cORR) assessedby investigator
(INV) according to RECIST 1.1. Considering a drop-out rate of 10%, 33 patients were required to
reject the null hypothesis that ORR is 20%or less, if the true ORR is 40% (two-sided alpha level
of 0.10, power 78.5%). Results: From Aug2020 to Dec2022, 37 pts were enrolled in 11 Brazilian
centers and 33 ptswere eligible for efficacy analysis.Median agewas 56y (range, 30-76), 64.9%
of pts had metastatic disease, 21.6% had recurrent disease, and 13.5% had locally advanced
disease. Efficacy results are presented in the table. cORR by INVwas 39.4% (95%CI 22.9-57.9);
with 1 complete response and 12 partial responses. cORR INV according to PD-L1 status (66.7%
in CPS 0% vs. 33.3% in CPS$1%); TMB status (75% in high vs. 36.4% in low); and HPV16 status
(HPV16 positive 55.6% vs. 35.0%). The most frequent genomic alterations detected by NGS
were: TP53(57.1%), CDKN2A (51.4%), and TERT (31.4%). Treatment-related adverse events
(AE) rate of any grade was 91.9% and grade 3-4 was 51.4%. Ten pts experienced Grade 5 AE,
none of them related to study treatment. Immune-related AEs of any grade was 21.6% and
grade 3-4 was 5.4%. 10.8% discontinued treatment due to AE. Conclusions: HERCULES is the
first trial to demonstrate the efficacy of ICI in advanced PSCC with manageable safety profile.
HPV16 and TMB are potential predictive biomarkers for efficacy. ICI combined with platinum-
based chemotherapy is a promising treatment for advanced PSCC warranting further inves-
tigation. Clinical trial information: NCT04224740. Research Sponsor: Merck Sharp & Dohme
LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), Brazil.
Efficacy Outcomes Total (n=33)
Confirmed ORR INV, % (95%CI) 39.4 (22.9-57.9)
Confirmed ORR Central Review, % (95% CI) 42.4 (25.5-60.8)
Unconfirmed ORR INV, % (95% CI) 45.5 (28.1-63.7)
CBR (CR+PR+SD ‡ 24 weeks) INV, % (95% CI) 45.5 (28.1-63.7)
Median DOR (95%CI), months 5.9 (4.4-9.0)
Median PFS INV (95% CI), months 5.4 (2.7-7.2)
Median OS (95% CI), months 9.6 (6.4-13.1)
Median follow-up 24.0months (95%CI 13.5-26.4); cut-off date
24Jan2024
GENITOURINARY CANCER—PROSTATE, TESTICULAR, AND PENILE
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http://www.clinicaltrials.gov/ct2/show/NCT04224740
http://crossmark.crossref.org/dialog/?doi=10.1200%2FJCO.2024.42.16_suppl.5009&domain=pdf&date_stamp=2024-05-29