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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumors
• Interventions: Biological: mRNA-4359; Biological: Pembrolizumab

• Registration Number: NCT05533697
• Lead Sponsor: ModernaTX, Inc.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-18
• Study First Submitted: 2022-08-23
• Study First Submitted QC: 2022-09-07
• Study First Posted: 2022-09-09
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20
• Primary Completion: 2027-12-08
• Study Completion: 2027-12-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 194

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1a (Dose Escalation): mRNA-4359 Alone	mRNA-4359	Participants will be administered mRNA-4359 at an applicable dose as monotherapy.
Arm 1b (Dose Confirmation): mRNA-4359 in Combination with Pembrolizumab	Pembrolizumab	Participants will be administered mRNA-4359 in combination with pembrolizumab at an applicable dose.
Arm 1b (Dose Confirmation): mRNA-4359 in Combination with Pembrolizumab	mRNA-4359	Participants will be administered mRNA-4359 in combination with pembrolizumab at an applicable dose.
Arm 2 (Dose Expansion): mRNA-4359 in Combination with Pembrolizumab	mRNA-4359	Participants will be administered mRNA-4359 in combination with pembrolizumab at an applicable dose.
Arm 2 (Dose Expansion): mRNA-4359 in Combination with Pembrolizumab	Pembrolizumab	Participants will be administered mRNA-4359 in combination with pembrolizumab at an applicable dose.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	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	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.

Trial Locations

Locations (26)

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

George Washington University; 🇺🇸 Washington, District of Columbia, United States

Orlando Health UF Health Cancer Center; 🇺🇸 Orlando, Florida, United States

The University of Chicago Medicine; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

John Theurer Cancer Center; 🇺🇸 Hackensack, New Jersey, United States

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

Oregon Health Sciences University; 🇺🇸 Portland, Oregon, United States

Sara Cannon Research Institute Tennessee; 🇺🇸 Nashville, Tennessee, United States

Southside Cancer Center; 🇦🇺 Miranda, New South Wales, Australia

Melanoma Institute Australia; 🇦🇺 Wollstonecraft, New South Wales, Australia

Austin Hospital; 🇦🇺 Melbourne, Victoria, Australia

One Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia

NEXT Oncology Barcelona; 🇪🇸 Barcelona, Spain

NEXT Oncology Madrid; 🇪🇸 Madrid, Spain

Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, Scotland, United Kingdom

Queen Elizabeth Hospital Birmingham; 🇬🇧 Birmingham, United Kingdom

University College London Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom

Guy's and St. Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom

Imperial College London; 🇬🇧 London, United Kingdom

Churchill Hospital; 🇬🇧 Oxford, United Kingdom

University Hospital Southampton NHS Foundation Trust; 🇬🇧 Southampton, United Kingdom