Long-term follow-up of standard-dose pembrolizumab plus reduced-dose ipilimumab in patients with advanced melanoma: KEYNOTE-029 Part 1B Academic Article uri icon


  • 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).


    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.


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


  • Carlino, Matteo S
  • Menzies, Alexander M
  • Atkinson, Victoria
  • Cebon, Jonathan S
  • Jameson, Michael B
  • Fitzharris, Bernard M
  • McNeil, Catriona M
  • Hill, Andrew G
  • Ribas, Antoni
  • Atkins, Michael B
  • Thompson, John A
  • Hwu, Wen-Jen
  • Hodi, F Stephen
  • Guminski, Alexander D
  • Kefford, Richard
  • Wu, Haiyan
  • Ibrahim, Nageatte
  • Homet Moreno, Blanca
  • Long, Georgina V

publication date

  • 2020