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

Advanced or Metastatic Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05017012
• Other study ID #: 3475A-C18
• Secondary ID: MK-3475A-C18jRCT
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 21, 2021
• Est. completion date: September 26, 2026

Study information

• Verified date: February 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study to assess the pharmacokinetics, safety, and tolerability of pembrolizumab formulated with MK-5180 when administered as a SC injection to participants with advanced solid tumors. Participants will receive SC injections of MK-3475A 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: September 26, 2026
• Est. primary completion date: September 26, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Biological:
• MK-3475A
MK-3475A is a fixed-dose formulation of pembrolizumab (either Conc1 or Conc2) and MK-5180 for SC administration.
• Pembrolizumab
Participants will receive pembrolizumab 400 mg IV.

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

Locations

Country	Name	City	State
Chile	Bradfordhill ( Site 0100)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 0101)	Santiago	Region M. De Santiago
Chile	James Lind Centro de Investigación del Cáncer ( Site 0102)	Temuco	Araucania
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 0020)	Budapest
Hungary	Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0021)	Budapest	Pest
Japan	National Hospital Organization Kyushu Cancer Center ( Site 0114)	Fukuoka
Japan	Kansai Medical University Hospital ( Site 0112)	Hirakata	Osaka
Japan	Saitama Prefectural Cancer Center ( Site 0110)	Ina-machi	Saitama
Japan	Shizuoka Cancer Center ( Site 0111)	Nagaizumi-cho,Sunto-gun	Shizuoka
Japan	Osaka International Cancer Institute ( Site 0113)	Osaka
Korea, Republic of	Samsung Medical Center ( Site 0063)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System ( Site 0062)	Seoul
South Africa	Cape Town Oncology Trials ( Site 0050)	Cape Town	Western Cape
South Africa	Medical Oncology Centre of Rosebank ( Site 0058)	Johannesburg	Gauteng
South Africa	CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 0051)	Port Elizabeth	Eastern Cape
South Africa	LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 0052)	Pretoria	Gauteng
South Africa	Steve Biko Academic Hospital-Medical Oncology ( Site 0057)	Pretoria	Gauteng
South Africa	Cancercare Rondebosch Oncology-Clinical trials ( Site 0055)	Rondebosch	Western Cape
South Africa	Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 0053)	Sandton	Gauteng
Spain	HOSPITAL CLÍNIC DE BARCELONA-Department of Medical Oncology ( Site 0043)	Barcelona	Cataluna
Spain	HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 0040)	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Virgen de la Victoria-Phase I Trials Unit ( Site 0042)	Málaga	Andalucia

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

Chile,  Hungary,  Japan,  Korea, Republic of,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Arms 1, 2, and 3: Pembrolizumab Trough Concentration (Ctrough) After MK-3475A Treatment	Ctrough is defined as the observed trough concentration measured during the absorption phase, prior to SC injection of MK-3475A. 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
Primary	Arms 1, 2, and 3: Pembrolizumab Maximum Plasma Concentration (Cmax) After MK-3475A Treatment	Cmax is defined as the maximum plasma concentration measured during the absorption phase, following SC injection of MK-3475A. 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
Primary	Arms 1, 2, and 3: Pembrolizumab Time of Maximum Plasma Concentration (Tmax) After MK-3475A Treatment	Tmax is defined as the time to maximum plasma concentration measured during the absorption phase, following SC injection of MK-3475A. 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
Primary	Arms 1, 2, and 3: Pembrolizumab Area under the Curve (AUC) After MK 3475A Treatment	AUC is defined as the area under the curve measured during the absorption phase, following SC injection of MK-3475A. 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
Primary	Arms 1 and 2: Pembrolizumab Bioavailability (F) After MK-3475A 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 MK-3475A. F will be reported for Arms 1 and 2.	At designated timepoints in Cycles 1 to 4 (up to 127 days). Cycle = 42 days
Primary	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)
Primary	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
Primary	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
Primary	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 MK-3475A 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
Primary	Arm 4: Pembrolizumab Trough Concentration (Ctrough) After MK 3475A Treatment	Ctrough is defined as the observed trough concentration measured during the absorption phase, prior to SC injection of MK-3475A. 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
Primary	Arm 4: Pembrolizumab Maximum Plasma Concentration (Cmax) After MK 3475A Treatment	Cmax is defined as the maximum plasma concentration measured during the absorption phase, following SC injection of MK-3475A. 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
Primary	Arm 4: Pembrolizumab Area under the Curve (AUC) After MK 3475A Treatment	AUC is defined as the area under the curve measured during the absorption phase, following SC injection of MK-3475A. 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
Secondary	Number of Participants Positive for Anti-Pembrolizumab Antibodies After MK-3475A 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.
Secondary	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
Secondary	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
Secondary	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 MK-3475A 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.
Secondary	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 MK-3475A 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
Secondary	Arm 3 (Japan): Pembrolizumab Bioavailability (F) After MK 3475A 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 MK-3475A. F will be reported for Arm 3.	At designated timepoints in Cycles 1-2 (up to 84 days). Cycle = 42 days

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary