Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Clinical Cancer Research Année : 2021

Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules

Georgina Long
Caroline Robert
Marcus Butler
Felix Couture
  • Fonction : Auteur
Matteo Carlino
  • Fonction : Auteur
Steven O'Day
  • Fonction : Auteur
Victoria Atkinson
  • Fonction : Auteur
Jonathan Cebon
Michael Brown
  • Fonction : Auteur
Andrew Hill
  • Fonction : Auteur
Geoffrey Gibney
  • Fonction : Auteur
Steven Mccune
Alexander Menzies
  • Fonction : Auteur
Cuizhen Niu
  • Fonction : Auteur
Nageatte Ibrahim
Blanca Homet Moreno
  • Fonction : Auteur
Adi Diab
  • Fonction : Auteur

Résumé

Abstract Purpose: Standard-dose pembrolizumab plus alternative-dose ipilimumab (1 mg/kg Q3W for 4 doses) were tolerable and had robust antitumor activity in advanced melanoma in cohort B of the phase 1 KEYNOTE-029 study. Cohort C evaluated standard-dose pembrolizumab with two other alternative ipilimumab regimens. Patients and Methods: Patients with treatment-naive unresectable stage III/IV melanoma were randomly assigned 1:1 to pembrolizumab 200 mg Q3W for ≤24 months plus ipilimumab 50 mg Q6W for 4 doses (PEM200+IPI50), or the same pembrolizumab regimen plus ipilimumab 100 mg Q12W for 4 doses (PEM200+IPI100). Primary end points were incidence of grade 3–5 treatment-related adverse events (TRAE) and objective response rate (ORR) per RECIST v1.1 by independent central review. Per protocol-defined thresholds, grade 3–5 TRAE incidence ≤26% indicated meaningful toxicity reduction and ORR ≥48% indicated no decrease in efficacy versus data reported for other PD-1 inhibitor/ipilimumab combinations. Results: Median follow-up on February 18, 2019, was 16.3 months in PEM200+IPI50 (N = 51) and 16.4 months in PEM200+IPI100 (N = 51). Grade 3–5 TRAEs occurred in 12 (24%) patients in PEM200+IPI50 and 20 (39%) in PEM200+IPI100. One patient in PEM200+IPI50 died from treatment-related autoimmune myocarditis. Immune-mediated AEs or infusion reactions occurred in 21 (42%) patients in PEM200+IPI50 and 28 (55%) in PEM200+IPI100. ORR was 55% in PEM200+IPI50; 61% in PEM200+IPI100. Conclusions: Pembrolizumab 200 mg Q3W plus ipilimumab 50 mg Q6W or 100 mg Q12W demonstrated antitumor activity above the predefined threshold; pembrolizumab plus ipilimumab 50 mg Q6W had lower incidence of grade 3–5 TRAEs than the predefined threshold, suggesting a reduction in toxicity. See related commentary by Jameson-Lee and Luke, p. 5153

Domaines

Cancer

Dates et versions

hal-04065982 , version 1 (12-04-2023)

Identifiants

Citer

Georgina Long, Caroline Robert, Marcus Butler, Felix Couture, Matteo Carlino, et al.. Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules. Clinical Cancer Research, 2021, 27 (19), pp.5280-5288. ⟨10.1158/1078-0432.CCR-21-0793⟩. ⟨hal-04065982⟩
10 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More