Clinical trial NCT05017012: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-08-23
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Arms 1, 2, and 3: Pembrolizumab Trough Concentration (Ctrough) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: 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: Arms 1, 2, and 3: Pembrolizumab Maximum Plasma Concentration (Cmax) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: 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: Arms 1, 2, and 3: Pembrolizumab Time of Maximum Plasma Concentration (Tmax) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: 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: Arms 1, 2, and 3: Pembrolizumab Area under the Curve (AUC) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: 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: Arms 1 and 2: Pembrolizumab Bioavailability (F) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: At designated timepoints in Cycles 1 to 4 (up to 127 days). Cycle = 42 days
measure: Arm 3 (Japan): Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
timeFrame: Up to 21 days of Cycle 1 (each cycle is 42 days)
measure: Arm 3 (Japan): Number of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 120 weeks
measure: Arm 3 (Japan): Number of Participants who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 108 weeks
measure: Arm 3 (Japan): Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
timeFrame: Day 1 of Cycle 1: Up to 60 minutes postdose. Cycle = 42 days
measure: Arm 4: Pembrolizumab Trough Concentration (Ctrough) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: 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
measure: Arm 4: Pembrolizumab Maximum Plasma Concentration (Cmax) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: 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
measure: Arm 4: Pembrolizumab Area under the Curve (AUC) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: 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:
measure: Number of Participants Positive for Anti-Pembrolizumab Antibodies After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: Predose (0-3 hours) on Day 1 of Cycles 1 and 3. Cycle = 42 days.
measure: Arms 1, 2, and 4: Number of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 120 weeks
measure: Arms 1, 2, and 4: Number of Participants who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 108 weeks
measure: Arms 1 and 2: Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
timeFrame: Day 1 of Cycles 1 and 3: Up to 60 minutes postdose. Cycle = 42 days.
measure: Arm 4: Number of Participants with Injection Site Signs and Symptoms as Assessed by the Subcutaneous Injection Site Signs and Symptoms Questionnaire
timeFrame: Cycle 1 Day 1: Up to 60 minutes postdose. Cycle = 21 days
measure: Arm 3 (Japan): Pembrolizumab Bioavailability (F) After pembrolizumab (+) berahyaluronidase alfa Treatment
timeFrame: At designated timepoints in Cycles 1-2 (up to 84 days). Cycle = 42 days
Other outcomes:
Locations:
city: Temuco
country: Chile
facility: James Lind Centro de Investigación del Cáncer ( Site 0102)
state: Araucania
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 0101)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill ( Site 0100)
state: Region M. De Santiago
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0021)
state: Pest
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 0020)
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital ( Site 0112)
state: Osaka
city: Ina-machi
country: Japan
facility: Saitama Prefectural Cancer Center ( Site 0110)
state: Saitama
city: Nagaizumi-cho,Sunto-gun
country: Japan
facility: Shizuoka Cancer Center ( Site 0111)
state: Shizuoka
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center ( Site 0114)
city: Osaka
country: Japan
facility: Osaka International Cancer Institute ( Site 0113)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System ( Site 0062)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0063)
city: Port Elizabeth
country: South Africa
facility: CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 0051)
state: Eastern Cape
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank ( Site 0058)
state: Gauteng
city: Pretoria
country: South Africa
facility: Steve Biko Academic Hospital-Medical Oncology ( Site 0057)
state: Gauteng
city: Pretoria
country: South Africa
facility: LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 0052)
state: Gauteng
city: Sandton
country: South Africa
facility: Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 0053)
state: Gauteng
city: Cape Town
country: South Africa
facility: Cape Town Oncology Trials ( Site 0050)
state: Western Cape
city: Rondebosch
country: South Africa
facility: Cancercare Rondebosch Oncology-Clinical trials ( Site 0055)
state: Western Cape
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria-Phase I Trials Unit ( Site 0042)
state: Andalucia
city: Barcelona
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA-Department of Medical Oncology ( Site 0043)
state: Cataluna
city: Madrid
country: Spain
facility: HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 0040)
state: Madrid, Comunidad De
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: