Clinical trial NCT06961006: A Clinical Study of V940 and Pembrolizumab (MK-3475) in People With Melanoma (V940-012/INTerpath-012)
Official title: A Phase 2, Randomized, Double-Blind, Placebo- and Active-Comparator-Controlled Clinical Study of V940 (mRNA-4157) Plus Pembrolizumab Versus Placebo Plus Pembrolizumab in Participants With First-Line Advanced Melanoma (INTerpath-012)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Malignant Melanoma
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2025-05-07
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Researchers want to learn if V940 with pembrolizumab can stop advanced melanoma from growing or spreading. Melanoma is a type of skin cancer. Advanced means the cancer has spread to other parts of the body and cannot be removed with surgery. A standard (or usual) treatment for advanced melanoma is immunotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. V940 is a study treatment designed to help a person's immune system attack their specific cancer. Pembrolizumab is an immunotherapy.

The goal of this study is to learn if people who receive V940 with pembrolizumab live longer without the cancer growing or spreading than people who receive placebo with pembrolizumab. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of a study treatment.


Eligibility criteria: Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has unresectable and histologically confirmed Stage III or IV cutaneous melanoma per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.
* Has been untreated for melanoma except if participant received prior adjuvant or neoadjuvant therapy with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein \[CTLA-4\], anti-programmed cell death 1 protein \[PD-1\] therapy or interferon), and only if relapse did not occur within 12 months after treatment discontinuation.
* Have documentation of serine/threonine-protein kinase B-raf (BRAF) V600-activating mutation status or had BRAF V600 mutation testing per local institutional standards during the screening period (participants with BRAF mutation positive melanoma as well as BRAF wild-type or unknown are eligible).
* Have the presence of at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment.
* Provides tumor tissue (preferably from a metastatic site and, if not available, from the primary tumor) that is suitable for next generation sequencing and biomarker analysis as required for this study.
* Participants with human immunodeficiency virus (HIV) 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 prior to randomization.
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has clinically significant heart failure, defined as New York Heart Association class III or IV, within the past 6 months, unless the disease is well controlled in the opinion of the investigator.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has ocular or mucosal melanoma.
* Received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks of the Screening blood sample (including the blood sample for V940 generation).
* Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, lymphocyte activation gene 3 \[LAG-3\], tumor necrosis factor receptors \[OX-40 or CD137\]), with some exceptions.
* Received prior systemic anticancer therapy for melanoma before randomization, with some exceptions.
* Received prior radiotherapy within 2 weeks of start of study intervention or has ongoing radiation related toxicities.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Received prior treatment with another universal or personalized cancer vaccine.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 36 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 6 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 6 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 6 years
measure: Number of Participants With ≥1 Adverse Event (AE)
timeFrame: Up to approximately 27 months
measure: Number of Participants Discontinuing From Study Therapy Due to AE
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Nedlands
country: Australia
facility: One Clinical Research
state: Western Australia
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: