A Clinical Study of Intismeran Autogene (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)

Overview

Researchers want to learn if intismeran autogene 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. Intismeran autogene 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 intismeran autogene 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.

Interventions

• Biological Intismeran autogene
  IM injection
• Biological Pembrolizumab
  IV infusion
• Other Placebo
  IM injection

Primary outcome measures

• Progression-free Survival (PFS) [Time frame: Up to approximately 36 months]

Secondary outcome measures (5)

• Objective Response Rate (ORR) [Time frame: Up to approximately 6 years]
• Duration of Response (DOR) [Time frame: Up to approximately 6 years]
• Overall Survival (OS) [Time frame: Up to approximately 6 years]
• Number of Participants With ≥1 Adverse Event (AE) [Time frame: Up to approximately 27 months]
• Number of Participants Discontinuing From Study Therapy Due to AE [Time frame: Up to approximately 24 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 5 centers

• Highlands Oncology Group ( Site 4042) — Springdale
• UCSF Medical Center at Mission Bay ( Site 4044) — San Francisco
• John Theurer Cancer Center at Hackensack University Medical Center ( Site 4047) — Hackensack
• Inova Schar Cancer Institute ( Site 4046) — Fairfax
• Fred Hutchinson Cancer Center ( Site 4041) — Seattle

Germany · 5 centers

• NCT ( Site 2065) — Heidelberg
• Universitätsklinikum Frankfurt Goethe-Universität ( Site 2063) — Frankfurt am Main
• Universitaetsklinikum Koeln ( Site 2064) — Cologne
• Universitaetsklinikum Essen ( Site 2061) — Essen
• Universitaetsklinikum Hamburg-Eppendorf ( Site 2060) — Hamburg

Israel · 4 centers

• HaEmek Medical Center ( Site 3003) — Afula
• Hadassah Medical Center ( Site 3001) — Jerusalem
• Rabin Medical Center ( Site 3002) — Petah Tikva
• Sheba Medical Center ( Site 3000) — Ramat Gan

Italy · 4 centers

• Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 3021) — Milan
• Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 3020) — Naples
• Istituto Oncologico Veneto IRCCS ( Site 3022) — Padova
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sac — Roma

Australia · 3 centers

• Blacktown Hospital ( Site 2001) — Blacktown
• Melanoma Institute Australia ( Site 2000) — Wollstonecraft
• One Clinical Research ( Site 2002) — Nedlands

France · 3 centers

• Centre Hospitalier Universitaire de Nice - Hôpital l'Archet-Dermatology Department ( Site — Nice
• Hôpital Saint-Louis ( Site 2041) — Paris
• Gustave Roussy ( Site 2040) — Villejuif

Greece · 3 centers

• General Hospital of Athens "Laiko" ( Site 2080) — Athens
• Metropolitan Hospital ( Site 2082) — Athens
• European Interbalkan Medical Center ( Site 2081) — Thessaloniki

Portugal · 3 centers

• Unidade Local de Saude Lisboa Ocidental - Hospital de São Francisco Xavier ( Site 4002) — Lisbon
• Unidade Local de Saude de Santa Maria - Hospital de Santa Maria ( Site 4001) — Lisbon
• Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 4000) — Porto

Spain · 3 centers

• Hospital Universitari Vall d'Hebron ( Site 3081) — Barcelona
• Hospital Clínic Barcelona ( Site 3080) — Barcelona
• Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 3082) — Madrid

Canada · 2 centers

• William Osler Health System (Brampton Civic Hospital) ( Site 2023) — Brampton
• Sunnybrook Research Institute ( Site 2022) — Toronto

Poland · 2 centers

• Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 3061) — Poznan
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 3060) — Warsaw

New Zealand · 1 center

• Harbour Cancer & Wellness ( Site 3040) — Auckland

Identifiers

NCT: NCT06961006 · V940-012 · V940-012 · INTerpath-012 · 2023-504923-20-00 · U1111-1290-3969

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗