Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors

Phase 1/2 Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors

The primary goal of this study is to assess the safety and tolerability of mRNA-4359 administered alone and in combination with pembrolizumab.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: Pembrolizumab; Biological: mRNA-4359

• Study Type: Interventional
• Enrollment (Estimated): 194
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Moderna Clinical Trials Support Center; Phone Number: 1-877-777-7187; Email: clinicaltrials@modernatx.com

Study Locations

• Australia
  • New South Wales
    • Wollstonecraft, New South Wales, Australia, 2065
      • Recruiting
      • Melanoma Institute Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3084
      • Recruiting
      • Austin Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research
• Spain
  • Barcelona, Spain, 08023
    • Recruiting
    • NEXT Oncology Barcelona
  • Madrid, Spain, 28223
    • Recruiting
    • NEXT Oncology Madrid
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Recruiting
      • Next Oncology
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Recruiting
    • Queen Elizabeth Hospital Birmingham
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guy's and St. Thomas' NHS Foundation Trust
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Imperial College London
  • Oxford, United Kingdom, Ox3 7LE
    • Recruiting
    • Churchill Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Recruiting
      • Beatson West of Scotland Cancer Centre
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Recruiting
      • George Washington University
  • Florida
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Orlando Health UF Health Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • Carolina BioOncology Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health Sciences University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sara Cannon Research Institute Tennessee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Dose Escalation (Arm 1a): Participant has histologically confirmed locally advanced or metastatic cancer (cutaneous melanoma, non-small-cell lung carcinoma (NSCLC), non-muscle invasive bladder cancer, head and neck squamous cell carcinoma, Microsatellite stable colorectal cancer (MSS CRC), basal cell carcinoma, or triple negative breast cancer) with measurable disease as determined by RECIST v1.1. Arm 1a participants must have received, and then progressed, relapsed, or been intolerant to, or ineligible for, at least 1 standard treatment regimen in the advanced or metastatic setting. Participants with a known driver mutation must have also received or been offered a mutation-directed therapy, where indicated. Participants must have a tumor lesion amenable to biopsy and must have another lesion that can be followed for response.

• Dose Confirmation (Arm 1b): Participant has histologically confirmed locally advanced or metastatic, and checkpoint inhibitor refractory melanoma or locally advanced or metastatic, and checkpoint inhibitor refractory NSCLC with measurable disease as determined by RECIST v1.1 who have disease progression after, at least 1 line of standard therapy (no limit to prior lines of therapy), and have been treated with or refused standard of care treatment. Must have primary refractory or acquired secondary resistance to prior immune checkpoint treatments. Primary refractory is defined as prior exposure to anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibody for at least 6 weeks but no more than 6 months with demonstration of progression on 2 separate scans at least 4 weeks apart but no more than 12 weeks apart and progression occurring within 6 months after first dose of anti-PD-1 antibody. Acquired secondary resistance must have confirmed objective response or prolonged stable disease (SD) (>6 months), followed by disease progression in the setting of ongoing treatment and confirmed progression on scans at least 4 weeks apart. Participants must have a tumor lesion amenable to biopsy and must have another lesion that can be followed for response.

  a. For NSCLC participants with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), proto-oncogene tyrosine-protein kinase reactive oxygen species (ROS1), or other actionable mutations for which there are approved targeted therapies, must have received prior approved targeted therapy or have been offered and declined approved targeted therapy.

• Dose Expansion Arm (Arm 2) only: Participant has histologically confirmed locally advanced, metastatic melanoma, or locally advanced or metastatic NSCLC with a PD-L1 TPS of ≥50% and with no EGFR or ALK positive tumor mutations, with measurable disease as determined by RECIST v1.1 and have not had any prior therapy for this cancer in this setting (that is, first line therapy). Participants must have a tumor lesion amenable to biopsy and must provide tumor biopsy sample at baseline (archival formalin-fixed, paraffin-embedded [FFPE]. If the participant is undergoing a new biopsy, they must have another lesion that can be followed for response.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
• Participant has adequate hematological and biological function

Key Exclusion Criteria:

• Participant has active central nervous system tumors or metastases.
• Participant has received treatment with prohibited medications (that is, concurrent anticancer therapy including other chemotherapy, radiation [local radiation for palliative care is permitted with approval from the Sponsor], hormonal anticancer treatment, biologic therapy, or immunotherapy) or investigational agents within 5 half-lives or 14 days prior to the first day of study intervention, whichever is shorter.
• Participant has required the use of additional immunosuppression other than corticosteroids for the management of an AE, has experienced recurrence of an AE if rechallenged, and currently requires maintenance doses of >10 milligrams (mg) prednisone or equivalent per day.
• Participant has any plan to receive a live attenuated vaccine during study intervention or has received a live vaccine within 30 days before the first dose of study intervention. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines and non-live coronavirus disease 2019 (COVID-19) for injection are generally allowed.
• Participant has reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and prespecified laboratory values.
• Participant who is pregnant, breastfeeding, or is of childbearing potential, defined as those who are capable of becoming pregnant who are not willing to employ a highly effective method of contraception during dosing and for 90 days after the last dose of mRNA-4359 or 120 days after the last dose of pembrolizumab, whichever is longer.
• Sexually active participants who refuse to use a condom during intercourse or participants who will not refrain from sperm donation while taking study intervention and for 90 days after the last dose of mRNA-4359 or 120 days after the last dose of pembrolizumab, whichever is longer.
• Participant has any unstable or clinically significant concurrent medical condition (for example, substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism) that would, in the opinion of the Investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol. Also including but not limited to, ongoing or active infection, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, active gastrointestinal bleeding or hemoptysis or history of bleeding disorder, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the participant to give written informed consent.
• Participant has concurrent enrollment in another clinical study (unless it is an observational noninterventional clinical study) or during the follow-up period of an interventional study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1a (Dose Escalation): mRNA-4359 Alone; Participants will be administered mRNA-4359 at an applicable dose as monotherapy.	Biological: mRNA-4359; Intramuscular Injection
Experimental: Arm 1b (Dose Confirmation): mRNA-4359 in Combination with Pembrolizumab; Participants will be administered mRNA-4359 in combination with pembrolizumab at an applicable dose.	Biological: Pembrolizumab; Intravenous infusion; Biological: mRNA-4359; Intramuscular Injection
Experimental: Arm 2 (Dose Expansion): mRNA-4359 in Combination with Pembrolizumab; Participants will be administered mRNA-4359 in combination with pembrolizumab at an applicable dose.	Biological: Pembrolizumab; Intravenous infusion; Biological: mRNA-4359; Intramuscular Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Dose Limiting Toxicities (DLTs)	Days 1-21 (Cycle 1)
Number of Participants with Adverse Events (AEs), AE of Special Interest (AESIs), and Serious AEs (SAEs)	Up to 34 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)		Day 1 up to approximately 27 months after the last dose of study treatment (duration of study treatment is up to nine 21-day cycles), or until disease progression, whichever occurs first
Disease Control Rate (DCR) Based on RECIST v1.1		Day 1 up to approximately 27 months after the last dose of study treatment (duration of study treatment is up to nine 21-day cycles), or until disease progression, whichever occurs first
Duration of Response (DOR) Based on RECIST v1.1		Day 1 up to approximately 27 months after the last dose of study treatment (duration of study treatment is up to nine 21-day cycles), or until disease progression, whichever occurs first
Progression Free Survival (PFS) Based on RECIST v1.1		Day 1 up to approximately 27 months after the last dose of study treatment (duration of study treatment is up to nine 21-day cycles), or until disease progression, whichever occurs first
Percent Change from Baseline in T Cell Profile in the Periphery and in the Tumor	Changes in CD3+CD8+, CD3+CD4+ and CD3+CD4+Foxp3+ cells will be measured by flow cytometry in peripheral blood and by immunohistochemistry in tumor.	Day 1 up to approximately 27 months after the last dose of study treatment (duration of study treatment is up to nine 21-day cycles), or until disease progression, whichever occurs first

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2022
• Primary Completion (Estimated): December 8, 2027
• Study Completion (Estimated): December 8, 2027

Study Registration Dates

• First Submitted: August 23, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 9, 2022

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Solid tumors; Pembrolizumab; Metastatic; Oncology; Locally advanced; Relapsed or refractory solid tumor malignancies
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: mRNA-4359-P101; 2023-504506-11-00 (Other Identifier: EU CT Number)

Drug and device information, study documents

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