A Study of Participant Reported Preference for Subcutaneous Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) Over Intravenous Pembrolizumab (MK-3475) Formulation in Multiple Tumor Types (MK-3475A-F11)

A Phase 2 Study to Evaluate Patient Reported Preference for Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Over Intravenous Pembrolizumab Formulation in Participants With Multiple Tumor Types (MK-3475A-F11)

The purpose of this study is to evaluate participant preference for coformulated hyaluronidase/pembrolizumab pembrolizumab (+) berahyaluronidase alfa [MK-3475A] administered subcutaneously (SC) over pembrolizumab [MK-3475] administered intravenously (IV) in participants with multiple tumor types. There will be no hypothesis testing in this study.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Renal Cell Carcinoma; Non-Small Cell Lung Cancer
• Intervention / Treatment: Biological: Pembrolizumab; Biological: Pembrolizumab (+) Berahyaluronidase alfa

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • San Juan, Argentina, J5400EBB
    • Instituto San Marcos ( Site 0305)
  • Buenos Aires
    • Mar del Plata, Buenos Aires, Argentina, B7600FZO
      • Instituto de Investigaciones Clínicas Mar del Plata ( Site 0300)
  • Buenos Aires F.D.
    • Buenos Aires, Buenos Aires F.D., Argentina, C1426ABP
      • Fundación Respirar ( Site 0302)
• Australia
  • New South Wales
    • Port Macquarie, New South Wales, Australia, 2444
      • Port Macquarie - Mid North Coast Cancer Institute-Medical Oncology ( Site 1001)
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital-Oncology and Haematology ( Site 1007)
• Chile
  • Los Lagos Region
    • Port Montt, Los Lagos Region, Chile, 5500243
      • Clínica Puerto Montt ( Site 0404)
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 7500921
      • FALP-UIDO ( Site 0401)
    • Santiago, Region M. de Santiago, Chile, 7500994
      • Oncovida ( Site 0403)
    • Santiago, Region M. de Santiago, Chile, 8330032
      • Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 0407)
    • Santiago, Region M. de Santiago, Chile, 8420383
      • Bradfordhill-Clinical Area ( Site 0402)
  • Región de Valparaíso
    • Viña del Mar, Región de Valparaíso, Chile, 2520598
      • ONCOCENTRO APYS-ACEREY ( Site 0400)
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile, 4800827
      • Centro Investigacion Cancer James Lind ( Site 0408)
• France
  • Auvergne-Rhône-Alpes
    • Lyon Cedex08, Auvergne-Rhône-Alpes, France, 69373
      • CENTRE LEON BERARD-onco dermatology ( Site 0600)
  • Calvados
    • Caen, Calvados, France, 14000
      • Centre Hospitalier Universitaire de Caen Normandie-DERMATOLOGY ( Site 0604)
  • Haute-Vienne
    • Limoges, Haute-Vienne, France, 87039
      • Clinique Francois Chenieux ( Site 0603)
  • Var
    • Toulon, Var, France, 83800 Cedex 9
      • HIA Sainte Anne-Pneumology ( Site 0601)
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75018
      • Hôpital Bichat - Claude-Bernard ( Site 0605)
• Japan
  • Tokyo, Japan, 162-8666
    • Tokyo Women's Medical University ( Site 1100)
  • Osaka
    • Sakai, Osaka, Japan, 599-8247
      • Bell Land General Hospital ( Site 1101)
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital-Cancer & Blood Research ( Site 1051)
  • Wellington, New Zealand, 6035
    • Bowen Hospital ( Site 1050)
• Poland
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-796
      • Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 0701)
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier
  • West Pomeranian Voivodeship
    • Koszalin, West Pomeranian Voivodeship, Poland, 75-581
      • Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0702)
    • Szczecin, West Pomeranian Voivodeship, Poland, 71-730
      • Zachodniopomorskie Centrum Onkologii ( Site 0703)
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Cancer Care Langenhoven Drive Oncology Centre ( Site 0808)
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • Medical Oncology Centre of Rosebank ( Site 0805)
    • Johannesburg, Gauteng, South Africa, 2196
      • Nosworthy Oncology ( Site 0807)
    • Pretoria, Gauteng, South Africa, 0001
      • Steve Biko Academic Hospital-Medical Oncology ( Site 0804)
    • Pretoria, Gauteng, South Africa, 0181
      • LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 0800)
    • Sandton, Gauteng, South Africa, 2196
      • Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 0801)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7570
      • Cape Town Oncology Trials ( Site 0802)
    • Cape Town, Western Cape, South Africa, 7700
      • CANCERCARE RONDEBOSCH ONCOLOGY-Cancercare Rondebosch Oncology ( Site 0806)
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01140
    • Adana Medical Park Seyhan Hastanesi-Medikal Onkoloji ( Site 0903)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universite Hastaneleri-oncology hospital ( Site 0900)
  • Ankara, Turkey (Türkiye), 06800
    • Ankara Bilkent Şehir Hastanesi-Medical Oncology ( Site 0901)
  • Izmir, Turkey (Türkiye), 35100
    • Ege Universitesi Hastanesi ( Site 0902)
• United States
  • Alabama
    • Alexander City, Alabama, United States, 35010
      • Russell Medical ( Site 0160)
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology ( Site 0121)
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group-Research Department ( Site 0133)
  • California
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care ( Site 0148)
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital-Clinical Research ( Site 0159)
    • Orange City, Florida, United States, 32763
      • Mid Florida Hematology and Oncology Center ( Site 0113)
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0112)
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology ( Site 0103)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a histologically- or cytologically-confirmed early stage or advanced/ metastatic solid tumor by pathology report and meet the following conditions based on tumor type:

  • Surgically resected Stage IIB and IIC (pathological or clinical), or III cutaneous melanoma per American Joint Committee on Cancer (AJCC) eighth edition.
  • Surgically resected renal cell carcinoma (RCC) with intermediate-high or high risk of recurrence as defined by the Fuhrman grading status.
  • Stage IV non-small cell lung cancer (NSCLC) per AJCC eight edition, with an anti-programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% determined using the Dako PD-L1 immunohistochemistry (IHC) 22C3 pharmDx diagnostic kit, and confirmation that epidermal growth factor receptor (EGFR-), anaplastic lymphoma kinase (ALK-), or c-ros oncogene 1 (ROS1)- directed therapy is not indicated as primary therapy.
• Has a life expectancy of at least 3 months.
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before randomization.
• Participants with history of hepatitis C virus (HCV) infection are eligible if have completed curative antiviral therapy at least 4 weeks before randomization and HCV viral load is undetectable at screening.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before the start of study intervention.

Exclusion Criteria:

• Non-small cell lung cancer (NSCLC) participants with a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
• Melanoma participants with ocular, mucosal, or conjunctival melanoma.
• Renal Cell Carcinoma (RCC) participants who have had major surgery, other than nephrectomy, within 12 weeks before randomization.
• Has received prior radiotherapy for RCC.
• RCC participants who have residual thrombus post nephrectomy in the vena renalis or vena cava.
• Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
• Received prior systemic anticancer therapy for their metastatic NSCLC. Note: Prior treatment with neoadjuvant or adjuvant therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
• Received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention.
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
• Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has active infection requiring systemic therapy.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has history of allogeneic tissue/solid organ transplant corticosteroids.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has not adequately recovered from major surgery or have ongoing surgical complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Pembrolizumab (+) Berahyaluronidase alfa SC →Pembrolizumab IV; In the Treatment Crossover Period: participants will first receive pembrolizumab (+) berahyaluronidase alfa SC for three 21-day cycles, followed by pembrolizumab IV for three 21-day cycles. After completion of the Treatment Crossover Period, participants will enter the Treatment Continuation Period where they will receive their preferred intervention for up to 17 21-day cycles (up to ~1 year) for renal cell carcinoma (RCC) and melanoma, and for up to 35 21-day cycles (up to ~2 years) for non-small cell lung cancer (NSCLC).	Biological: Pembrolizumab; Administered via IV infusion; Other Names: MK-3475, KEYTRUDA®; Biological: Pembrolizumab (+) Berahyaluronidase alfa; Fixed dose coformulated product of hyaluronidase/pembrolizumab adminstered via SC injection.; Other Names: MK-3475A
Active Comparator: Arm B: Pembrolizumab IV→pembrolizumab (+) berahyaluronidase alfa SC; In the Treatment Crossover Period: participants will first receive pembrolizumab IV for three 21-day cycles, followed by pembrolizumab (+) berahyaluronidase alfa SC for three 21-day cycles. After completion of the Treatment Crossover Period, participants will enter the Treatment Continuation Period where they will receive their preferred intervention for up to 17 21-day cycles (up to ~1 year) for renal cell carcinoma (RCC) and melanoma, and for up to 35 21-day cycles (up to ~2 years) for non-small cell lung cancer (NSCLC).	Biological: Pembrolizumab; Administered via IV infusion; Other Names: MK-3475, KEYTRUDA®; Biological: Pembrolizumab (+) Berahyaluronidase alfa; Fixed dose coformulated product of hyaluronidase/pembrolizumab adminstered via SC injection.; Other Names: MK-3475A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Prefer Pembrolizumab Plus Berahyaluronidase Alfa Subcutaneous (SC) As Assessed By Patient Preference Questionnaire (PPQ) Question 1	The PPQ is an instrument that has been developed from participant interviews and includes questions to evaluate directly from participants their preference regarding mode of administration, as well as the strength of the preference, and the reason for the preference. The PPQ does not have any pre-defined scale or associated numerical scoring and answer choices are qualitative. Question 1 in the PPQ evaluates participants' preferred method of administration with response options of IV, SC or "no preference". As pre-specified by the protocol, the percentage of participants who preferred SC administration (participant preference rate [PPR]) was reported out of all randomized participants who received all 3 doses of Pembrolizumab IV and Pembrolizumab SC during treatment crossover period and answered at least question 1 of the PPQ on Cycle 6 Day 1 (Day 106).	Day 106

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Preferred SC Administration According to Most Frequent Reasons of Preference As Assessed by PPQ Question 3	The PPQ is an instrument that has been developed from patient interviews and includes questions to evaluate directly from participants their preference regarding mode of administration, as well as the strength of the preference, and the reason for the preference. PPQ Question 3 evaluated 2 main reasons for participants' preference for one of the administration methods (SC or IV), with response options including "feels less emotionally distressing", "requires less time in the clinic", and "lower level injection-site pain". As pre-specified by the supplemental statistical analysis plan (sSAP), the most frequent reasons for preferring SC administration as assessed by PPQ Question 3 were reported among all participants preferring SC in each treatment arm. Treatment arms A (Pembrolizumab Plus Berahyaluronidase alfa SC followed by Pembrolizumab IV) and B (Pembrolizumab IV followed by Pembrolizumab plus Berahyaluronidase alfa SC) were defined as treatment sequence arms in the protocol.	Day 106
Percentage of Participants That Were Satisfied or Dissatisfied With the SC Method of Administration According to Level of Satisfaction, As Assessed by Therapy Administration Satisfaction Questionnaire - Subcutaneous (TASQ-SC) Question 1	The TASQ SC is a 12-item questionnaire that asks questions regarding different aspects of participants' satisfaction with SC administration, experiences related to administration, convenience, and time. The TASQ SC does not have any pre-defined scale or associated numerical scoring and answer choices are qualitative. Question 1 in the TASQ SC evaluates participants' satisfaction or dissatisfaction with SC administration. As pre-specified by the sSAP, the percentage of participants was reported for each response to TASQ-SC Question 1 according to level of satisfaction, for each treatment arm. Treatment arms A (Pembrolizumab Plus Berahyaluronidase alfa SC followed by Pembrolizumab IV) and B (Pembrolizumab IV followed by Pembrolizumab plus Berahyaluronidase alfa SC) were defined as treatment sequence arms in the protocol.	Up to approximately Day 106
Percentage of Participants That Were Satisfied or Dissatisfied With the IV Method of Administration According to Level of Satisfaction, As Assessed by Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) Question 1	The TASQ IV is a 12-item questionnaire that asks questions regarding different aspects of participants' satisfaction with IV administration, experiences related to administration, convenience, and time. The TASQ IV does not have any pre-defined scale or associated numerical scoring and answer choices are qualitative. Question 1 in the TASQ IV evaluates participants' satisfaction or dissatisfaction with IV administration. As pre-specified by the sSAP, the percentage of participants was reported for each response to TASQ-IV Question 1 according to level of satisfaction, for each treatment arm. Treatment arms A (Pembrolizumab Plus Berahyaluronidase alfa SC followed by Pembrolizumab IV) and B (Pembrolizumab IV followed by Pembrolizumab plus Berahyaluronidase alfa SC) were defined as treatment sequence arms in the protocol.	Up to approximately Day 106
Percentage of Participants Who Chose Pembrolizumab (+) Berahyaluronidase Alfa SC or Pembrolizumab IV for the Treatment Continuation Period on the Participant Choice Questionnaire	The Participant Choice Questionnaire offered participants SC or IV treatment administration choices for the Treatment Continuation Period of the study, and was administered on Day 106 after study intervention administration. As pre-specified by the sSAP, the percentage of participants who chose either SC or IV treatment for the Treatment Continuation Period in the study was reported out of all randomized participants who chose to receive treatment intervention in the Treatment Continuation Period.	Day 106
Number of Participants Who Experience an Adverse Event (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. As pre-specified by the protocol, the number of participants who experience an AE will be reported for the overall study according to treatment arm, defined as a treatment sequence arm in the protocol (i.e., "Pembrolizumab Plus Berahyaluronidase alfa SC followed by Pembrolizumab IV" and "Pembrolizumab IV followed by Pembrolizumab plus Berahyaluronidase alfa SC").	Up to ~27 months
Number of Participants Who Discontinue Study Drug 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. As pre-specified by the protocol, the number of participants who discontinue study drug due to an AE will be reported for the overall study according to treatment arm, defined as a treatment sequence arm in the protocol (i.e., "Pembrolizumab Plus Berahyaluronidase alfa SC followed by Pembrolizumab IV" and "Pembrolizumab IV followed by Pembrolizumab plus Berahyaluronidase alfa SC").	Up to ~24 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2023
• Primary Completion (Actual): April 9, 2025
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: October 19, 2023
• First Submitted That Met QC Criteria: October 19, 2023
• First Posted (Actual): October 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Urologic Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: 3475A-F11; U1111-1293-0814 (Registry Identifier: UTN); MK-3475A-F11 (Other Identifier: MSD); jRCT2051230147 (Registry Identifier: Japan Registry of Clinical Trials (jRCT)); 2023-506017-22-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No