e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

KEYMAKER-U02: Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Melanoma (#399)

Georgina V. Long 1 , Reinhard Dummer 2 , Anna C. Pavlick 3 , Michael A. Postow 4 , Antoni Ribas 5 , Caroline Robert 6 , Richard A. Scolyer 7 , Janis M. Taube 8 , Michael Tetzlaff 9 , Shu-Chih Su 10 , Rohini Singh 10 , Scott J. Diede 10 , Hussein Abdul-Hassan Tawbi 11
  1. Medical Oncology and Translational Research, Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia
  2. Dermatology, Skin Cancer Center, University Hospital of Zürich, Zürich, Switzerland
  3. Medicine and Dermatology, Edward and Sandra Meyers Cancer Center, Weill Cornell Medicine, New York, NY, USA
  4. Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  5. Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
  6. Dermatology Committee, Gustave Roussy and Paris-Sud University, Villejuif, France
  7. Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
  8. Division of Dermatopathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  9. Dermatology and Pathology, UCSF Dermatopathology Service, San Francisco, CA, USA
  10. Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA
  11. Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Aims: Pembrolizumab is SOC for advanced and adjuvant stage III melanoma. Treatment options are needed to improve outcomes for patients with brain metastases (BMs), resistance to SOC, or resectable stage melanoma.

Methods: KEYMAKER-U02 is a rolling-arm, open-label, adaptive design, phase 1/2 study of investigational agents ± pembrolizumab or pembrolizumab alone in melanoma. Four substudies are recruiting.

Substudy 02A: Patients with unresectable stage III/IV PD-1–refractory melanoma are randomized to ≥1 investigational agent(s) ± pembrolizumab. Planned enrollment: ~100 patients/arm.

Substudy 02B: Patients with unresectable treatment-naive stage III/IV melanoma are randomized 2:1 to ≥1 investigational agent(s) ± pembrolizumab or pembrolizumab alone (stratification: baseline LDH, prior adjuvant anti–PD-1). Planned enrollment: ~90 patients in combination arms, ~45 in the pembrolizumab arm.

Substudy 02C: Patients with stage IIIB/IIIC/IIID melanoma eligible for neoadjuvant therapy are randomized to ≥1 investigational agent(s) ± pembrolizumab or pembrolizumab alone. Surgical resection will occur 6 weeks after first neoadjuvant dose. Planned enrollment: ~25 patients in combination arms, ~15 in the pembrolizumab arm.

Substudy 02D: Patients have stage IV melanoma, 1-5 measurable BMs by RECIST v1.1 confirmed by BICR, no neurologic symptoms of BM, and ≤3 lines of prior treatment. Patients in PD-1–naive or PD-1–exposed cohorts are randomized to ≥1 investigational agent(s) + pembrolizumab. Planned enrollment: ~50 patients per arm (≤100 PD-1–naive cohort).

Treatment duration: ≤2 years in substudies 02A, 02B, and 02D; ≤1 year in 02C. Primary end points are safety; ORR by BICR per RECIST v1.1 for 02A, 02B, and 02D; and pathological CR (pCR) by central review for 02C. Secondary end points are DOR for 02A and 02B; RFS, near pCR, and pathological PR rate for 02C; and DOR and PFS by BICR per RECIST v1.1, BM response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM), and BM-DOR per RANO-BM for 02D.