Pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma: Results of the KEYNOTE-029 expansion cohort.
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.9506
ISSN1527-7755
AutoresGeorgina V. Long, Victoria Atkinson, Jonathan Cebon, Michael B. Jameson, Bernie Fitzharris, Catriona M. McNeil, Andrew G. Hill, Antoni Ribas, Michael B. Atkins, John A. Thompson, Wen‐Jen Hwu, F. Stephen Hodi, Alexander M. Menzies, Alexander Guminski, Richard Kefford, Xinxin Shu, Scot Ebbinghaus, Nageatte Ibrahim, Matteo S. Carlino,
Tópico(s)Immunotherapy and Immune Responses
Resumo9506 Background: Pembro (MK-3475), an anti–PD-1 antibody that prevents PD-1 from binding to its ligands, PD-L1 and PD-L2, is approved in several countries for treating advanced melanoma. In KEYNOTE-006, pembro showed superior OS over the anti–CTLA-4 inhibitor ipi. In a phase 3 trial, combination therapy with reduced-dose nivolumab (anti–PD-1) and standard-dose ipi showed higher ORR and longer PFS than either checkpoint inhibitor alone but was associated with increased toxicity. Preliminary data from the phase 1 KEYNOTE-029 study (NCT02089685) suggested that standard-dose pembro + reduced-dose ipi was safe and provided robust antitumor activity. Here, we present data from a larger population of patients (pts) treated with pembro + ipi in the KEYNOTE-029 expansion cohort. Methods: Eligible pts had advanced melanoma, ECOG PS 0-1, no active brain metastases, and no prior immune checkpoint inhibitor therapy. Pts received pembro 2 mg/kg Q3W + ipi 1 mg/kg Q3W for 4 doses, then pembro 2 mg/kg Q3W until intolerable toxicity, progression, or 2 y. Response was assessed by RECIST v1.1 at wk 12, every 6 wk until wk 30, then every 12 wk thereafter. Results: Of 153 pts enrolled in the expansion, 107 had ≥18 wk of follow-up (median 6.4 mo, range 4.3-9.4) by the Oct 26, 2015, data cutoff and were eligible for analysis. 18% of pts had elevated LDH, 55% had stage M1c disease, 36% were BRAFV600mutant, 13% received ≥1 prior therapy, and 12% received a prior BRAF ± MEK inhibitor; 84% had PD-L1–positive tumors (ie, ≥1% staining in tumor and adjacent immune cells). 79 pts (74%) received all 4 ipi doses; 73 pts (68%) remained on pembro. 41 pts (38%) had ≥1 grade 3-4 drug-related AE (DRAE); 68% of these DRAEs resolved by data cutoff. DRAEs led to discontinuation of pembro and ipi in 9 pts (8%), ipi alone in 11 (10%), and pembro alone in 4 (4%); there were no treatment-related deaths. Immune-mediated AEs of any grade and grade 3-4 severity occurred in 57 (53%) and 21 (20%) pts. ORR by investigator review was 57%, with 5 (5%) CR and 56 (52%) PR; by central review, ORR was 51%, with 9% CR and 42% PR. Conclusions: Pembro 2 mg/kg in combination with 4 doses of ipi 1 mg/kg has a manageable toxicity profile and provides robust antitumor activity in pts with advanced melanoma. Clinical trial information: NCT02089685.
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