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)

NCT ID: NCT05017012

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-21

Study Completion Date

2026-09-26

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced or Metastatic Solid Tumors

Keywords

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Programmed Cell Death-1 (PD1, PD-1) Programmed Death-Ligand 1 (PDL1, PD-L1)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

None (Open-label)

Study Groups

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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.

Group Type EXPERIMENTAL

Pembrolizumab (+) Berahyaluronidase alfa

Intervention Type BIOLOGICAL

Pembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration.

Pembrolizumab

Intervention Type BIOLOGICAL

Participants will receive pembrolizumab 400 mg IV.

Pemetrexed

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Participants may receive 5 mg orally twice daily continuously as background SOC treatment during the study, as applicable to their diagnosis.

Cisplatin

Intervention Type 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.

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.

Group Type EXPERIMENTAL

Pembrolizumab (+) Berahyaluronidase alfa

Intervention Type BIOLOGICAL

Pembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration.

Pembrolizumab

Intervention Type BIOLOGICAL

Participants will receive pembrolizumab 400 mg IV.

Pemetrexed

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Participants may receive 5 mg orally twice daily continuously as background SOC treatment during the study, as applicable to their diagnosis.

Cisplatin

Intervention Type 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.

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.

Group Type EXPERIMENTAL

Pembrolizumab (+) Berahyaluronidase alfa

Intervention Type BIOLOGICAL

Pembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration.

Pembrolizumab

Intervention Type BIOLOGICAL

Participants will receive pembrolizumab 400 mg IV.

Pemetrexed

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type 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.

Cisplatin

Intervention Type 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.

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.

Group Type EXPERIMENTAL

Pembrolizumab (+) Berahyaluronidase alfa

Intervention Type BIOLOGICAL

Pembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration.

Interventions

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Pembrolizumab (+) Berahyaluronidase alfa

Pembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration.

Intervention Type BIOLOGICAL

Pembrolizumab

Participants will receive pembrolizumab 400 mg IV.

Intervention Type BIOLOGICAL

Pemetrexed

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.

Intervention Type DRUG

Carboplatin

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.

Intervention Type DRUG

Paclitaxel

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.

Intervention Type DRUG

Nab-paclitaxel

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.

Intervention Type DRUG

Axitinib

Participants may receive 5 mg orally twice daily continuously as background SOC treatment during the study, as applicable to their diagnosis.

Intervention Type DRUG

Cisplatin

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.

Intervention Type DRUG

Other Intervention Names

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MK-3475A Keytruda MK-3475 Alimta Taxol Albumin-bound paclitaxel Platinol-AQ

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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FALP-UIDO ( Site 0101)

Santiago, Region M. de Santiago, Chile

Site Status

Bradfordhill ( Site 0100)

Santiago, Region M. de Santiago, Chile

Site Status

James Lind Centro de Investigación del Cáncer ( Site 0102)

Temuco, Región de la Araucanía, Chile

Site Status

Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0021)

Budapest, Pest County, Hungary

Site Status

Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 0020)

Budapest, , Hungary

Site Status

Kansai Medical University Hospital ( Site 0112)

Hirakata, Osaka, Japan

Site Status

Saitama Prefectural Cancer Center ( Site 0110)

Ina-machi, Saitama, Japan

Site Status

Shizuoka Cancer Center ( Site 0111)

Nagaizumi-cho,Sunto-gun, Shizuoka, Japan

Site Status

National Hospital Organization Kyushu Cancer Center ( Site 0114)

Fukuoka, , Japan

Site Status

Osaka International Cancer Institute ( Site 0113)

Osaka, , Japan

Site Status

CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 0051)

Port Elizabeth, Eastern Cape, South Africa

Site Status

Medical Oncology Centre of Rosebank ( Site 0058)

Johannesburg, Gauteng, South Africa

Site Status

Steve Biko Academic Hospital-Medical Oncology ( Site 0057)

Pretoria, Gauteng, South Africa

Site Status

LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 0052)

Pretoria, Gauteng, South Africa

Site Status

Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 0053)

Sandton, Gauteng, South Africa

Site Status

Cape Town Oncology Trials ( Site 0050)

Cape Town, Western Cape, South Africa

Site Status

Cancercare Rondebosch Oncology-Clinical trials ( Site 0055)

Rondebosch, Western Cape, South Africa

Site Status

Severance Hospital, Yonsei University Health System ( Site 0062)

Seoul, , South Korea

Site Status

Samsung Medical Center ( Site 0063)

Seoul, , South Korea

Site Status

Hospital Universitario Virgen de la Victoria-Phase I Trials Unit ( Site 0042)

Málaga, Andalusia, Spain

Site Status

HOSPITAL CLÍNIC DE BARCELONA-Department of Medical Oncology ( Site 0043)

Barcelona, Catalonia, Spain

Site Status

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 0040)

Madrid, Madrid, Comunidad de, Spain

Site Status

Countries

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Chile Hungary Japan South Africa South Korea Spain

References

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Cohen GL, Coetzee C, Walton CA, Reig Torras O, Chul Cho B, McAdam G, Rojas CI, Medina Rodriguez L, Papai Z, Chan SW, Rapoport BL, Caglevic C, Yanez Weber P, Takahashi T, Kurata T, Song G, Cohen JW, Akala OO, Khanyile R. Pharmacokinetics and bioavailability of pembrolizumab with berahyaluronidase alfa for subcutaneous administration in participants with advanced or metastatic solid tumors: The phase 1 study 3475A-C18. Eur J Cancer. 2025 Aug 9:115709. doi: 10.1016/j.ejca.2025.115709. Online ahead of print.

Reference Type DERIVED
PMID: 40957773 (View on PubMed)

Related Links

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Other Identifiers

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MK-3475A-C18

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2031220507

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-001569-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475A-C18

Identifier Type: -

Identifier Source: org_study_id