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)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 1

Conditions: Advanced or Metastatic Solid Tumors

Treatments: Drug: Carboplatin; Drug: Nab-paclitaxel; Drug: Pemetrexed; Drug: Axitinib; Drug: Cisplatin; Biological: Pembrolizumab; Biological: Pembrolizumab (+) Berahyaluronidase alfa; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT05017012

2021-001569-18 (EudraCT Number)

jRCT2031220507 (Registry Identifier)

MK-3475A-C18 (Other Identifier)

3475A-C18

Details and patient eligibility

About

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.

Enrollment: 72 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor.
• Can provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• Has a measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
• Demonstrates adequate organ function.

Exclusion criteria

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication.
• Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention, or has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related AEs).
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has an active infection requiring therapy.
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Has known hepatitis B or C infections or known to be positive for hepatitis B surface antigen (HBsAg)/hepatitis B virus deoxyribonucleic acid (DNA) or hepatitis C antibody and ribonucleic acid (RNA)
• Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study.
• Has not fully recovered from any effects of major surgery without significant detectable infection.
• Has symptomatic ascites or pleural effusion.
• Has preexisting peripheral neuropathy that is >Grade 2 by latest NCI CTCAE version 5.
• Has a known sensitivity to recombinant hyaluronidase or other form of hyaluronidase.
• Has a history of severe hypersensitivity reaction (eg, generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis) to pemetrexed, cisplatin, axitinib, carboplatin, paclitaxel, or nab-paclitaxel.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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72 participants in 4 patient groups

Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Biological: Pembrolizumab (+) Berahyaluronidase alfa

Biological: Pembrolizumab

Drug: Cisplatin

Drug: Axitinib

Drug: Nab-paclitaxel

Drug: Pemetrexed

Drug: Carboplatin

Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Biological: Pembrolizumab (+) Berahyaluronidase alfa

Biological: Pembrolizumab

Drug: Cisplatin

Drug: Axitinib

Drug: Nab-paclitaxel

Drug: Pemetrexed

Drug: Carboplatin

Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Biological: Pembrolizumab (+) Berahyaluronidase alfa

Biological: Pembrolizumab

Drug: Cisplatin

Drug: Nab-paclitaxel

Drug: Pemetrexed

Drug: Carboplatin

Pembrolizumab Conc1 [dose 2]/Berahyaluronidase alfa

Experimental group

Description:

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.

Treatment:

Biological: Pembrolizumab (+) Berahyaluronidase alfa