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

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 2

Conditions: Melanoma; Renal Cell Carcinoma; Non-Small Cell Lung Cancer

Treatments: Biological: Pembrolizumab; Biological: Pembrolizumab co-formulated with hyaluronidase

Study type: Interventional

Funder types: Industry

Identifiers

NCT06099782

U1111-1293-0814 (Other Identifier)

jRCT2051230147 (Registry Identifier)

MK-3475A-F11 (Other Identifier)

2023-506017-22 (Registry Identifier)

3475A-F11

Details and patient eligibility

About

The purpose of this study is to evaluate participant preference for coformulated hyaluronidase/pembrolizumab (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.

Enrollment: 144 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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144 participants in 2 patient groups

Arm A: MK-3475A SC →Pembrolizumab IV

Experimental group

Description:

In the treatment crossover period, participants will receive MK-3475A SC followed by pembrolizumab IV. After completion of the treatment crossover period, participants will enter the treatment continuation period, where they will receive their preferred intervention for up to \~1 year for renal cell carcinoma (RCC) and melanoma and for up to \~2 years for non-small cell lung cancer (NSCLC).

Treatment:

Biological: Pembrolizumab co-formulated with hyaluronidase

Biological: Pembrolizumab

Arm B: Pembrolizumab IV→MK-3475A SC

Active Comparator group

Description:

In the treatment crossover period, participants will receive pembrolizumab IV followed by MK-3475A SC. After completion of the treatment crossover period, participants will enter the treatment continuation period, where they will receive their preferred intervention for up to \~1 year for RCC and melanoma and for up to \~2 years for NSCLC.

Treatment:

Biological: Pembrolizumab co-formulated with hyaluronidase

Biological: Pembrolizumab