Long-term Follow-up of Standard-Dose Pembrolizumab Plus Reduced-Dose Ipilimumab in Patients with Advanced Melanoma: KEYNOTE-029 Part 1B.

Abstract

PURPOSE:

Combination therapy with reduced-dose programmed death 1 inhibitor plus standard-dose cytotoxic T-lymphocyte-associated antigen 4 inhibitor demonstrated efficacy, but substantial toxicity, in melanoma. We present long-term results of part 1B of KEYNOTE-029, which assessed safety and efficacy of standard-dose pembrolizumab plus reduced-dose ipilimumab in advanced melanoma.

PATIENTS AND METHODS:

Part 1B was an expansion cohort of the open-label, phase Ib portion of KEYNOTE-029. Eligible patients had advanced melanoma and no previous immune checkpoint inhibitor therapy. Patients received pembrolizumab 2 mg/kg (amended to 200 mg) every 3 weeks plus ipilimumab 1 mg/kg every 3 weeks (four cycles), then pembrolizumab alone for up to 2 years. Primary end point was safety; secondary end points included objective response rate (ORR), progression-free survival (PFS), duration of response (DOR), and overall survival (OS).

RESULTS:

A total of 153 patients received at least one dose of pembrolizumab plus ipilimumab. At a median follow-up of 36.8 months, 71.9% had received four doses of ipilimumab and 30.7% had completed 2 years of pembrolizumab; 26.1% completed both treatments. Treatment-related adverse events occurred in 96.1% (47.1% grade 3/4; no deaths), leading to discontinuation of one or both study drugs in 35.9%. ORR was 62.1% with 42 (27.5%) complete and 53 (34.6%) partial responses. Median DOR was not reached; 36-month ongoing response rate was 84.2%. Median PFS and OS were not reached; 36-month rates were 59.1% and 73.4%, respectively.

CONCLUSIONS:

Standard-dose pembrolizumab plus reduced-dose ipilimumab demonstrated robust antitumor activity, durable response, and favorable long-term survival with manageable toxicity.

• Authors: Matteo S Carlino, Alexander M Menzies, Victoria Atkinson, Jonathan S Cebon, Michael B Jameson, Bernard M Fitzharris, Catriona M McNeil, Andrew G Hill, Antoni Ribas, Michael B Atkins, John A Thompson, Wen-Jen Hwu, F Stephen Hodi, Alexander D Guminski, Richard Kefford, Haiyan Wu, Nageatte Ibrahim, Blanca Homet Moreno, Georgina V Long
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 19 Pg. 5086-5091 (10 01 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 32605909 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• CD274 protein, human
• CTLA-4 Antigen
• CTLA4 protein, human
• Ipilimumab
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• pembrolizumab

Topics

• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• B7-H1 Antigen (antagonists & inhibitors, genetics)
• CTLA-4 Antigen (antagonists & inhibitors, genetics)
• Cohort Studies
• Female
• Follow-Up Studies
• Humans
• Ipilimumab (administration & dosage)
• Male
• Melanoma (drug therapy, genetics, pathology)
• Middle Aged
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, genetics)
• Progression-Free Survival