A Study to Evaluate the Bioavailability of Pembrolizumab (MK-3475) Via Subcutaneous (SC) Injection of Pembrolizumab Formulated With Berahyaluronidase Alfa (MK-5180) [MK-3475A] In Advanced Solid Tumors (MK-3475A-C18)

Sponsor
Merck Sharp & Dohme LLC
Study ID
NCT05017012
Phase
PHASE1
Status
Completed

Conditions

  • Advanced or Metastatic Solid Tumors

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pembrolizumab (+) Berahyaluronidase alfa — BIOLOGICAL
    Pembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration.
  • Pembrolizumab — BIOLOGICAL
    Participants will receive pembrolizumab 400 mg IV.
  • Pemetrexed — DRUG
    Participants may receive 500 mg/m\^2 IV every 3 weeks (Q3W) Day 1 and Day 22 of Cycles 1 to 18 as background SOC treatment during the study, as applicable to their diagnosis.
  • Carboplatin — DRUG
    Participants may receive 5 mg/mL/min IV (nonsquamous) or 6 mg/mL/min IV (squamous) on Day 1 of each 21-day cycle for 4 cycles as background SOC treatment during the study, as applicable to their diagnosis.
  • Paclitaxel — DRUG
    Participants may receive 200 mg/m\^2 IV on Day 1 of each 21-day cycle for 4 cycles as background SOC treatment during the study, as applicable to their diagnosis.
  • Nab-paclitaxel — DRUG
    Participants may receive 100 mg/m2 IV on Day 1, 8, and 15 of each 21-day cycle for 4 cycles as background SOC treatment during the study, as applicable to their diagnosis.
  • Axitinib — DRUG
    Participants may receive 5 mg orally twice daily continuously as background SOC treatment during the study, as applicable to their diagnosis.
  • Cisplatin — DRUG
    Participants may receive 75 mg/m\^2 IV on Day 1 of each 21-day cycle for 4 cycles as background SOC treatment during the study, as applicable to their diagnosis.

Study Details

This is a study to assess the pharmacokinetics, safety, and tolerability of pembrolizumab formulated with berahyaluronidase when administered as a SC injection to participants with advanced solid tumors. Participants will receive SC injections of pembrolizumab (+) berahyaluronidase alfa containing one of 2 different concentrations (Conc) of pembrolizumab, Conc1 and Conc2, corresponding to a pembrolizumab dose level of dose 1 for Arms 1, 2, and 3 and dose 2 for Arm 4.

Key Dates

Start date
Sep 21, 2021
Status verified
Jun 2026
Primary completion
May 19, 2026
Completion
May 19, 2026

Study Design

Enrollment
142 participants (actual)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa
    Participants receive pembrolizumab (+) berahyaluronidase alfa (pembrolizumab Conc1 \[dose 1\] + berahyaluronidase alfa) SC on Day 1 of Cycles 1 and 3 plus 400 mg pembrolizumab intravenously (IV) on Day 1 of Cycles 2 and 4 to 18, with or without background standard of care (SOC) chemotherapy as appropriate for the indication. A cycle is 42 days.
  • Experimental: Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa
    Participants receive pembrolizumab (+) berahyaluronidase alfa (pembrolizumab Conc2 \[dose 1\] + Berahyaluronidase alfa) SC on Day 1 of Cycles 1 and 3 plus 400 mg pembrolizumab IV on Day 1 of Cycles 2 and 4 to 18, with or without background SOC chemotherapy as appropriate for the indication. A cycle is 42 days.
  • Experimental: Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy
    Participants in Japan receive pembrolizumab (+) berahyaluronidase alfa (pembrolizumab Conc1 \[dose 1\] + berahyaluronidase alfa) SC on Day 1 of Cycle 1, with background SOC chemotherapy, and then receive 400 mg pembrolizumab IV on Day 1 of Cycles 2 to 18, with background SOC chemotherapy. A cycle is 42 days.
  • Experimental: Pembrolizumab Conc1 [dose 2]/Berahyaluronidase alfa
    Participants receive pembrolizumab (+) berahyaluronidase alfa (pembrolizumab Conc1 \[dose 2\] + berahyaluronidase alfa) SC on Day 1 of Cycles 1 to 35 without background standard of care (SOC) chemotherapy. A cycle is 21 days.

Primary Outcome Measure

Arms 1, 2, and 3: Pembrolizumab Trough Concentration (Ctrough) After pembrolizumab (+) berahyaluronidase alfa Treatment [ Time Frame: Predose (0-3 hours) and postdose (0-10 minutes) on Cycle 1 Day 1; any time on Cycle 1 Days 2, 3, 4, 5, 6, 8, 10, 15, 22, 29, and 36. Cycle = 42 days ]

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