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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3475A-C18 | Other Identifier | MSD | |
| jRCT2031220507 | Registry Identifier | Japan Registry of Clinical Trials (jRCT) | |
| 2023-505340-19-00 | Registry Identifier | EU CT | |
| U1111-1291-5232 | Registry Identifier | UTN | |
| 2021-001569-18 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab (+) Berahyaluronidase alfa | Biological | Pembrolizumab (+) Berahyaluronidase alfa is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and berahyaluronidase alfa for SC administration. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Predose (0-3 hours) on Day 1 of Cycles 1 and 3. Cycle = 42 days. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| James Lind Centro de Investigación del Cáncer ( Site 0102) | Temuco | Araucania | 4800827 | Chile | ||
| FALP-UIDO ( Site 0101) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40957773 | Derived | 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. |
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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None (Open-label)
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| 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. |
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| Pembrolizumab | Biological | Participants will receive pembrolizumab 400 mg IV. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| Axitinib | Drug | Participants may receive 5 mg orally twice daily continuously as background SOC treatment during the study, as applicable to their diagnosis. |
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| 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. |
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| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 |
| 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. | 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. | 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. | 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. | 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. | At designated timepoints in Cycles 1-2 (up to 84 days). Cycle = 42 days |
| Santiago |
| Region M. de Santiago |
| 7500921 |
| Chile |
| Bradfordhill ( Site 0100) | Santiago | Region M. de Santiago | 8420383 | Chile |
| Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0021) | Budapest | Pest County | 1122 | Hungary |
| Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 0020) | Budapest | 1062 | Hungary |
| Kansai Medical University Hospital ( Site 0112) | Hirakata | Osaka | 573-1191 | Japan |
| Saitama Prefectural Cancer Center ( Site 0110) | Ina-machi | Saitama | 362-0806 | Japan |
| Shizuoka Cancer Center ( Site 0111) | Nagaizumi-cho,Sunto-gun | Shizuoka | 411-8777 | Japan |
| National Hospital Organization Kyushu Cancer Center ( Site 0114) | Fukuoka | 811-1395 | Japan |
| Osaka International Cancer Institute ( Site 0113) | Osaka | 541-8567 | Japan |
| CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 0051) | Port Elizabeth | Eastern Cape | 6055 | South Africa |
| Medical Oncology Centre of Rosebank ( Site 0058) | Johannesburg | Gauteng | 2196 | South Africa |
| Steve Biko Academic Hospital-Medical Oncology ( Site 0057) | Pretoria | Gauteng | 0001 | South Africa |
| LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 0052) | Pretoria | Gauteng | 0181 | South Africa |
| Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 0053) | Sandton | Gauteng | 2196 | South Africa |
| Cape Town Oncology Trials ( Site 0050) | Cape Town | Western Cape | 7570 | South Africa |
| Cancercare Rondebosch Oncology-Clinical trials ( Site 0055) | Rondebosch | Western Cape | 7700 | South Africa |
| Severance Hospital, Yonsei University Health System ( Site 0062) | Seoul | 03722 | South Korea |
| Samsung Medical Center ( Site 0063) | Seoul | 06351 | South Korea |
| Hospital Universitario Virgen de la Victoria-Phase I Trials Unit ( Site 0042) | Málaga | Andalusia | 29010 | Spain |
| HOSPITAL CLÍNIC DE BARCELONA-Department of Medical Oncology ( Site 0043) | Barcelona | Catalonia | 08036 | Spain |
| HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 0040) | Madrid | Madrid, Comunidad de | 28009 | Spain |
| Plain Language Summary | View source |
| ID | Term |
|---|---|
| C565324 | Parkinson Disease 4, Autosomal Dominant Lewy Body |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D000068437 | Pemetrexed |
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| C520255 | 130-nm albumin-bound paclitaxel |
| D000068196 | Albumin-Bound Paclitaxel |
| D000077784 | Axitinib |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D011506 | Proteins |
| D001549 | Benzamides |
| D000577 | Amides |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D007191 | Indazoles |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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