Advanced or Metastatic Solid TumorsPhase 1NCT05017012
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)
A Phase 1 study testing Pembrolizumab (+) Berahyaluronidase alfa, Pembrolizumab and Pemetrexed in people with Advanced or Metastatic Solid Tumors, run by Merck Sharp & Dohme LLC at 22 sites in 6 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumors
- What is being tested?
- Pembrolizumab (+) Berahyaluronidase alfa, Pembrolizumab and Pemetrexed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 22 sitesin 6 countries
- Study dates
- 21 Sep 2021to 19 May 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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 locations and contacts
22 sites in 6 countries.
22 sites in 6 countries
South Africa7 sites
Cape Town Oncology Trials ( Site 0050)
Cape Town, Western Cape, 7570
Medical Oncology Centre of Rosebank ( Site 0058)
Johannesburg, Gauteng, 2196
CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 0051)
Port Elizabeth, Eastern Cape, 6055
Steve Biko Academic Hospital-Medical Oncology ( Site 0057)
Pretoria, Gauteng, 0001
LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 0052)
Pretoria, Gauteng, 0181
Cancercare Rondebosch Oncology-Clinical trials ( Site 0055)
Rondebosch, Western Cape, 7700
Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 0053)
Sandton, Gauteng, 2196
Japan5 sites
National Hospital Organization Kyushu Cancer Center ( Site 0114)
Fukuoka, 811-1395
Kansai Medical University Hospital ( Site 0112)
Hirakata, Osaka, 573-1191
Saitama Prefectural Cancer Center ( Site 0110)
Ina-machi, Saitama, 362-0806
Shizuoka Cancer Center ( Site 0111)
Nagaizumi-cho,Sunto-gun, Shizuoka, 411-8777
Osaka International Cancer Institute ( Site 0113)
Osaka, 541-8567
Chile3 sites
FALP-UIDO ( Site 0101)
Santiago, Region M. de Santiago, 7500921
Bradfordhill ( Site 0100)
Santiago, Region M. de Santiago, 8420383
James Lind Centro de Investigación del Cáncer ( Site 0102)
Temuco, Araucania, 4800827
Spain3 sites
HOSPITAL CLÍNIC DE BARCELONA-Department of Medical Oncology ( Site 0043)
Barcelona, Catalonia, 08036
HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 0040)
Madrid, Madrid, Comunidad de, 28009
Hospital Universitario Virgen de la Victoria-Phase I Trials Unit ( Site 0042)
Málaga, Andalusia, 29010
Hungary2 sites
Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0021)
Budapest, Pest County, 1122
Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 0020)
Budapest, 1062
South Korea2 sites
Severance Hospital, Yonsei University Health System ( Site 0062)
Seoul, 03722
Samsung Medical Center ( Site 0063)
Seoul, 06351
About this study
Official title: A Phase 1 Clinical Study to Evaluate the Bioavailability of Pembrolizumab Via Subcutaneous Injection of MK-3475A, a Formulation of Pembrolizumab With MK-5180, in Participants With Advanced Solid Tumors
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.
- Conditions
- Advanced or Metastatic Solid Tumors
- Being tested
- Pembrolizumab (+) Berahyaluronidase alfa, Pembrolizumab, Pemetrexed, Carboplatin, Paclitaxel
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Medical subject headings
- Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab (+) Berahyaluronidase alfaBiological
Also called MK-3475A
Pembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration.
PembrolizumabBiological
Also called Keytruda, MK-3475
Participants will receive pembrolizumab 400 mg IV.
PemetrexedDrug
Also called Alimta
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.
CarboplatinDrug
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.
PaclitaxelDrug
Also called Taxol
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-paclitaxelDrug
Also called Albumin-bound 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.
AxitinibDrug
Participants may receive 5 mg orally twice daily continuously as background SOC treatment during the study, as applicable to their diagnosis.
CisplatinDrug
Also called Platinol-AQ
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 group | Role | What they receive |
|---|---|---|
| Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa | Experimental | 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. Receives: Biological: Pembrolizumab (+) Berahyaluronidase alfa; Biological: Pembrolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Axitinib; Drug: Cisplatin |
| Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa | Experimental | 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. Receives: Biological: Pembrolizumab (+) Berahyaluronidase alfa; Biological: Pembrolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Axitinib; Drug: Cisplatin |
| Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy | Experimental | 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. Receives: Biological: Pembrolizumab (+) Berahyaluronidase alfa; Biological: Pembrolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Cisplatin |
| Pembrolizumab Conc1 [dose 2]/Berahyaluronidase alfa | Experimental | 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. Receives: Biological: Pembrolizumab (+) Berahyaluronidase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arms 1, 2, and 3: Pembrolizumab Trough Concentration (Ctrough) After pembrolizumab (+) berahyaluronidase alfa Treatment
Ctrough is defined as the observed trough concentration measured during the absorption phase, prior to SC injection of pembrolizumab (+) berahyaluronidase alfa. Ctrough will be reported for Arms 1, 2, and 3.
Measured: 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
Arms 1, 2, and 3: Pembrolizumab Maximum Plasma Concentration (Cmax) After pembrolizumab (+) berahyaluronidase alfa Treatment
Cmax is defined as the maximum plasma concentration measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. Cmax will be reported for Arms 1, 2, and 3.
Measured: 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
Arms 1, 2, and 3: Pembrolizumab Time of Maximum Plasma Concentration (Tmax) After pembrolizumab (+) berahyaluronidase alfa Treatment
Tmax is defined as the time to maximum plasma concentration measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. Tmax will be reported for Arms 1, 2, and 3.
Measured: 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
Arms 1, 2, and 3: Pembrolizumab Area under the Curve (AUC) After pembrolizumab (+) berahyaluronidase alfa Treatment
AUC is defined as the area under the curve measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. AUC will be reported for Arms 1, 2, and 3.
Measured: 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
Arms 1 and 2: Pembrolizumab Bioavailability (F) After pembrolizumab (+) berahyaluronidase alfa Treatment
Bioavailability (F) is defined as the percentage (or the fraction F) of an administered SC dose that reaches the systemic circulation unaltered during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. F will be reported for Arms 1 and 2.
Measured: At designated timepoints in Cycles 1 to 4 (up to 127 days). Cycle = 42 days
Arm 3 (Japan): Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment: Grade (Gr) 4 nonhematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia: Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia associated with clinically significant bleeding; thrombocytopenia requiring platelet transfusion; anemia requiring red blood cell transfusion; Nonhematologic AE Gr ≥3 in severity, with exceptions; Any Gr 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions; Gr 3 or Gr 4 febrile neutropenia; Prolonged delay (>2 weeks) during Cycle 1 Days 1 to 21 due to treatment-related toxicity; Treatment-related toxicity resulting in participant study treatment discontinuation during Cycle 1 Days 1 to 21; Gr 5 toxicity.
Measured: Up to 21 days of Cycle 1 (each cycle is 42 days)
Arm 3 (Japan): Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with an AE will be reported for Arm 3.
Measured: Up to approximately 120 weeks
Arm 3 (Japan): Number of Participants who Discontinue Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported for Arm 3.
Measured: Up to approximately 108 weeks
Arm 3 (Japan): Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
Approximately 60 minutes post injection of pembrolizumab (+) berahyaluronidase alfa on Day 1 of Cycles 1 and 3, participants are to complete the Subcutaneous Injection Site Signs and Symptoms Questionnaire. Participants are asked to rate any pain, itching, swelling and redness they experience at the pembrolizumab SC injection site from "None" to "Severe". The number of participants who experience an injection site sign or symptom will be reported for Arm 3.
Measured: Day 1 of Cycle 1: Up to 60 minutes postdose. Cycle = 42 days
Arm 4: Pembrolizumab Trough Concentration (Ctrough) After pembrolizumab (+) berahyaluronidase alfa Treatment
Ctrough is defined as the observed trough concentration measured during the absorption phase, prior to SC injection of pembrolizumab (+) berahyaluronidase alfa. Ctrough will be reported for Arm 4.
Measured: Predose (0-3 hours) on Day 1 of Cycles 1 and 6; any time on Days 2, 4, 6, 10, and 15 of Cycles 1 and 6. Cycle = 21 days
Arm 4: Pembrolizumab Maximum Plasma Concentration (Cmax) After pembrolizumab (+) berahyaluronidase alfa Treatment
Cmax is defined as the maximum plasma concentration measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. Cmax will be reported for Arm 4.
Measured: Predose (0-3 hours) on Day 1 of Cycles 1 and 6; any time on Days 2, 4, 6, 10, and 15 of Cycles 1 and 6. Cycle = 21 days
Arm 4: Pembrolizumab Area under the Curve (AUC) After pembrolizumab (+) berahyaluronidase alfa Treatment
AUC is defined as the area under the curve measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. AUC will be reported for Arm 4.
Measured: Predose (0-3 hours) on Day 1 of Cycles 1 and 6; any time on Days 2, 4, 6, 10, and 15 of Cycles 1 and 6. Cycle = 21 days
Secondary outcomes (6)
Number of Participants Positive for Anti-Pembrolizumab Antibodies After pembrolizumab (+) berahyaluronidase alfa Treatment
Blood samples are to be collected at designated time points for the determination of the presence or absence of anti-pembrolizumab antibodies. The percentage of participants who develop anti-pembrolizumab antibodies will be reported.
Measured: Predose (0-3 hours) on Day 1 of Cycles 1 and 3. Cycle = 42 days.
Arms 1, 2, and 4: Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with an AE will be reported for Arms 1, 2, and 4.
Measured: Up to approximately 120 weeks
Arms 1, 2, and 4: Number of Participants who Discontinue Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported for Arms 1, 2, and 4.
Measured: Up to approximately 108 weeks
Arms 1 and 2: Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
Approximately 60 minutes post injection of pembrolizumab (+) berahyaluronidase alfa on Day 1 of Cycles 1 and 3, participants are to complete the Subcutaneous Injection Site Signs and Symptoms Questionnaire. Participants are asked to rate any pain, itching, swelling and redness they experience at the pembrolizumab SC injection site from "None" to "Severe". The number of participants who experience an injection site sign or symptom will be reported for Arms 1 and 2.
Measured: Day 1 of Cycles 1 and 3: Up to 60 minutes postdose. Cycle = 42 days.
Arm 4: Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
Approximately 60 minutes post injection of pembrolizumab (+) berahyaluronidase alfa on Day 1 of Cycle 1, participants are to complete the Subcutaneous Injection Site Signs and Symptoms Questionnaire. Participants are asked to rate any pain, itching, swelling and redness they experience at the pembrolizumab SC injection site from "None" to "Severe". The number of participants who experience an injection site sign or symptom will be reported for Arm 4.
Measured: Cycle 1 Day 1: Up to 60 minutes postdose. Cycle = 21 days
Arm 3 (Japan): Pembrolizumab Bioavailability (F) After pembrolizumab (+) berahyaluronidase alfa Treatment
Bioavailability (F) is defined as the percentage (or the fraction F) of an administered SC dose that reaches the systemic circulation unaltered during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. F will be reported for Arm 3.
Measured: At designated timepoints in Cycles 1-2 (up to 84 days). Cycle = 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2021
- Study start21 Sep 2021
- Primary completion19 May 2026
- Study completion19 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05017012
- Sponsor's protocol ID
- 3475A-C18
- Other IDs
- MK-3475A-C18, jRCT2031220507, 2023-505340-19-00, U1111-1291-5232, 2021-001569-18, 2023
- Status last verified
- Jun 2026
- First submitted
- 18 Aug 2021
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
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 Nov 17;230:115709. doi: 10.1016/j.ejca.2025.115709. Epub 2025 Aug 9.
PubMed 40957773
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Clinical Study to Evaluate the Bioavailability of Pembrolizumab Via Subcutaneous Injection of MK-3475A, a Formulation of Pembrolizumab With MK-5180, in Participants With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT05017012
- Acronym / sponsor ID
- 3475A-C18
- Conditions
- Advanced or Metastatic Solid Tumors
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 21 Sep 2021 (actual)
- Primary completion
- 19 May 2026 (actual)
- Study completion
- 19 May 2026 (actual)
- First posted
- 23 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa | Experimental | Biological: Pembrolizumab (+) Berahyaluronidase alfa, Biological: Pembrolizumab, Drug: Pemetrexed, Drug: Carboplatin, Drug: Paclitaxel, Drug: Nab-paclitaxel, Drug: Axitinib, Drug: CisplatinParticipants 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. |
| Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa | Experimental | Biological: Pembrolizumab (+) Berahyaluronidase alfa, Biological: Pembrolizumab, Drug: Pemetrexed, Drug: Carboplatin, Drug: Paclitaxel, Drug: Nab-paclitaxel, Drug: Axitinib, Drug: CisplatinParticipants 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. |
| Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy | Experimental | Biological: Pembrolizumab (+) Berahyaluronidase alfa, Biological: Pembrolizumab, Drug: Pemetrexed, Drug: Carboplatin, Drug: Paclitaxel, Drug: Nab-paclitaxel, Drug: CisplatinParticipants 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. |
| Pembrolizumab Conc1 [dose 2]/Berahyaluronidase alfa | Experimental | Biological: Pembrolizumab (+) Berahyaluronidase alfaParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab (+) Berahyaluronidase alfaAlso: MK-3475APembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration. | Biological | Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa, Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy, Pembrolizumab Conc1 [dose 2]/Berahyaluronidase alfa, Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa |
| PembrolizumabAlso: Keytruda, MK-3475Participants will receive pembrolizumab 400 mg IV. | Biological | Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa, Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy, Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa |
| PemetrexedAlso: AlimtaParticipants 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. | Drug | Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa, Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy, Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa |
| CarboplatinParticipants 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. | Drug | Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa, Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy, Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa |
| PaclitaxelAlso: TaxolParticipants 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. | Drug | Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa, Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy, Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa |
| Nab-paclitaxelAlso: Albumin-bound paclitaxelParticipants 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. | Drug | Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa, Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy, Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa |
| AxitinibParticipants may receive 5 mg orally twice daily continuously as background SOC treatment during the study, as applicable to their diagnosis. | Drug | Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa, Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa |
| CisplatinAlso: Platinol-AQParticipants 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. | Drug | Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa, Pembrolizumab Conc1 [dose 1]/Berahyaluronidase alfa + SOC Chemotherapy, Pembrolizumab Conc2 [dose 1]/Berahyaluronidase alfa |
Primary outcome
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
Ctrough is defined as the observed trough concentration measured during the absorption phase, prior to SC injection of pembrolizumab (+) berahyaluronidase alfa. Ctrough will be reported for Arms 1, 2, and 3.
Arms 1, 2, and 3: Pembrolizumab Maximum Plasma Concentration (Cmax) 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
Cmax is defined as the maximum plasma concentration measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. Cmax will be reported for Arms 1, 2, and 3.
Arms 1, 2, and 3: Pembrolizumab Time of Maximum Plasma Concentration (Tmax) 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
Tmax is defined as the time to maximum plasma concentration measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. Tmax will be reported for Arms 1, 2, and 3.
Arms 1, 2, and 3: Pembrolizumab Area under the Curve (AUC) 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
AUC is defined as the area under the curve measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. AUC will be reported for Arms 1, 2, and 3.
Arms 1 and 2: Pembrolizumab Bioavailability (F) After pembrolizumab (+) berahyaluronidase alfa Treatment
Time frame: At designated timepoints in Cycles 1 to 4 (up to 127 days). Cycle = 42 days
Bioavailability (F) is defined as the percentage (or the fraction F) of an administered SC dose that reaches the systemic circulation unaltered during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. F will be reported for Arms 1 and 2.
Arm 3 (Japan): Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
Time frame: Up to 21 days of Cycle 1 (each cycle is 42 days)
DLT is defined as any of the following toxicities, if assessed by the investigator to be related to study treatment: Grade (Gr) 4 nonhematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia: Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia associated with clinically significant bleeding; thrombocytopenia requiring platelet transfusion; anemia requiring red blood cell transfusion; Nonhematologic AE Gr ≥3 in severity, with exceptions; Any Gr 3 or 4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, or if abnormality leads to hospitalization, persists for >1 week or results in drug-induced liver injury with exceptions; Gr 3 or Gr 4 febrile neutropenia; Prolonged delay (>2 weeks) during Cycle 1 Days 1 to 21 due to treatment-related toxicity; Treatment-related toxicity resulting in participant study treatment discontinuation during Cycle 1 Days 1 to 21; Gr 5 toxicity.
Arm 3 (Japan): Number of Participants with Adverse Events (AEs)
Time frame: Up to approximately 120 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with an AE will be reported for Arm 3.
Arm 3 (Japan): Number of Participants who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 108 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported for Arm 3.
Arm 3 (Japan): Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
Time frame: Day 1 of Cycle 1: Up to 60 minutes postdose. Cycle = 42 days
Approximately 60 minutes post injection of pembrolizumab (+) berahyaluronidase alfa on Day 1 of Cycles 1 and 3, participants are to complete the Subcutaneous Injection Site Signs and Symptoms Questionnaire. Participants are asked to rate any pain, itching, swelling and redness they experience at the pembrolizumab SC injection site from "None" to "Severe". The number of participants who experience an injection site sign or symptom will be reported for Arm 3.
Arm 4: Pembrolizumab Trough Concentration (Ctrough) After pembrolizumab (+) berahyaluronidase alfa Treatment
Time frame: Predose (0-3 hours) on Day 1 of Cycles 1 and 6; any time on Days 2, 4, 6, 10, and 15 of Cycles 1 and 6. Cycle = 21 days
Ctrough is defined as the observed trough concentration measured during the absorption phase, prior to SC injection of pembrolizumab (+) berahyaluronidase alfa. Ctrough will be reported for Arm 4.
Arm 4: Pembrolizumab Maximum Plasma Concentration (Cmax) After pembrolizumab (+) berahyaluronidase alfa Treatment
Time frame: Predose (0-3 hours) on Day 1 of Cycles 1 and 6; any time on Days 2, 4, 6, 10, and 15 of Cycles 1 and 6. Cycle = 21 days
Cmax is defined as the maximum plasma concentration measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. Cmax will be reported for Arm 4.
Arm 4: Pembrolizumab Area under the Curve (AUC) After pembrolizumab (+) berahyaluronidase alfa Treatment
Time frame: Predose (0-3 hours) on Day 1 of Cycles 1 and 6; any time on Days 2, 4, 6, 10, and 15 of Cycles 1 and 6. Cycle = 21 days
AUC is defined as the area under the curve measured during the absorption phase, following SC injection of pembrolizumab (+) berahyaluronidase alfa. AUC will be reported for Arm 4.
6 secondary outcomes
Number of Participants Positive for Anti-Pembrolizumab Antibodies After pembrolizumab (+) berahyaluronidase alfa Treatment
Time frame: Predose (0-3 hours) on Day 1 of Cycles 1 and 3. Cycle = 42 days.
Arms 1, 2, and 4: Number of Participants with Adverse Events (AEs)
Time frame: Up to approximately 120 weeks
Arms 1, 2, and 4: Number of Participants who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 108 weeks
Arms 1 and 2: Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
Time frame: Day 1 of Cycles 1 and 3: Up to 60 minutes postdose. Cycle = 42 days.
Arm 4: Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
Time frame: Cycle 1 Day 1: Up to 60 minutes postdose. Cycle = 21 days
Arm 3 (Japan): Pembrolizumab Bioavailability (F) After pembrolizumab (+) berahyaluronidase alfa Treatment
Time frame: At designated timepoints in Cycles 1-2 (up to 84 days). Cycle = 42 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- Derived from this study: PubMed 40957773Cohen 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 Nov 17;230:115709. doi: 10.1016/j.ejca.2025.115709. Epub 2025 Aug 9.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
22 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab (+) Berahyaluronidase alfa, Pembrolizumab and Pemetrexed in people with Advanced or Metastatic Solid Tumors, run by Merck Sharp & Dohme LLC at 22 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in South Africa, Japan, Chile, Spain, Hungary and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05017012, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026.