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

Plain English Summary

Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors is a Phase 2 clinical trial sponsored by ModernaTX, Inc. studying Advanced Solid Tumors. This trial tests a new drug called mRNA-4359, alone or with existing immune therapies, for advanced solid tumors. It is for patients with specific types of advanced cancers, including melanoma, lung, bladder, head and neck, colorectal, basal cell, and triple-negative breast cancer. Participation involves receiving the study drug(s) and regular medical check-ups, including biopsies and scans. Alternative treatments may include standard chemotherapy, targeted therapies, or other immunotherapies, depending on the cancer type and prior treatments. The trial aims to enroll 361 participants.

Official Summary

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

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older (or 12 and older for one specific arm) with specific advanced solid tumors. Patients must have had their cancer progress after, or be unable to tolerate, standard treatments. Certain criteria apply based on specific cancer types, prior treatments, and PD-L1 expression levels. Patients with active brain tumors or metastases are generally excluded. This trial is studying Advanced Solid Tumors, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will determine the safest dose of the new drug and how well it works, either alone or with other treatments, by looking at side effects and tumor shrinkage. The specific primary outcome measures are: Arms 1a and 1b: Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of mRNA-4359 (Days 1-21 (Cycle 1)); Arms 1, 2a, 2b, and 2c: Number of Participants with Dose Limiting Toxicities (DLTs) (Days 1-21 (Cycle 1)); Arms 1, 2a, 2b, and 2c: Number of Participants with Adverse Events (AEs), AE of Special Interest (AESIs), and Serious AEs (SAEs) (Up to 27 months); Arm 2d: Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (Day 1 up to 60 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to find new ways to treat advanced cancers that haven't responded to current therapies, potentially filling a gap for patients with limited options. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Advanced Solid Tumors, where improved treatment options are needed.

Investor Insight

This trial signals investment in novel mRNA-based cancer therapies, a rapidly growing field, with potential to compete with established immunotherapies if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific cancer types and stages included, and if your medical history makes you a good candidate. Understand the potential side effects of mRNA-4359 and the combination therapies, and how often you'll need to visit the clinic. Be prepared for potential biopsies and imaging scans to monitor your cancer's response to treatment. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 361 participants

Interventions

• BIOLOGICAL: mRNA-4359 — Intramuscular Injection
• BIOLOGICAL: Pembrolizumab — Intravenous infusion
• BIOLOGICAL: Ipilimumab — Intravenous infusion
• BIOLOGICAL: Nivolumab — Intravenous infusion

Primary Outcomes

• Arms 1a and 1b: Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of mRNA-4359 (Days 1-21 (Cycle 1))
• Arms 1, 2a, 2b, and 2c: Number of Participants with Dose Limiting Toxicities (DLTs) (Days 1-21 (Cycle 1))
• Arms 1, 2a, 2b, and 2c: Number of Participants with Adverse Events (AEs), AE of Special Interest (AESIs), and Serious AEs (SAEs) (Up to 27 months)
• Arm 2d: Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (Day 1 up to 60 months)

Secondary Outcomes

• Arms 1, 2a, 2b, and 2c: ORR Based on Investigator Assessment Per RECIST v1.1 (Day 1 up to 27 months)
• Arms 1, 2a, 2b, and 2c: Disease Control Rate (DCR) Based on Investigator Assessment Per RECIST v1.1 (Day 1 up to 27 months)
• Arms 1, 2a, 2b, and 2c: Duration of Response (DOR) Based on Investigator Assessment Per RECIST v1.1 (Day 1 up to 27 months)
• Arms 1, 2a, 2b, and 2c: Progression Free Survival (PFS) Based on Investigator Assessment Per RECIST v1.1 (Day 1 up to 27 months)
• Arms 1, 2a, 2b, and 2c: Percent Change from Baseline in T Cell Profile in the Tumor (Baseline up to 27 months)

Full Eligibility Criteria

Key Inclusion Criteria:

* Males or females ≥18 years of age who have provided written informed consent prior to completing any study-specific procedure. For Arm 2d, participants ≥12 years are eligible with informed consent/assent.
* Dose Escalation (Arm 1a): Participant has histologically confirmed locally advanced or metastatic cancer (cutaneous melanoma, 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 CPI refractory melanoma or locally advanced or metastatic, and CPI refractory NSCLC with measurable disease as determined by RECIST v1.1 who has disease progression after, at least 1 line of standard therapy (no limit to prior lines of therapy), and has been treated with or refused standard of care treatment. Participants in PD arm Group 2 must also have PD-L1 TPS ≥1%. Participants 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)/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.

  1. For NSCLC participants with known EGFR, ALK, proto-oncogene tyrosine-protein kinase reactive oxygen species (ROS1), or other actionable mutations for which there are approved targeted therapies, participants must have received prior approved targeted therapy or have been offered and declined approved targeted therapy.
  2. Expansion of the melanoma Arm 1b cohort (up to approximately 16 additional evaluable participants) will require prospective central testing of Screening tumor biopsies to confirm PD-L1 TPS ≥1% for eligibility.
* Dose Expansion Arms (Arm 2): Participant has histologically confirmed:

  1. Arm 2a: Locally advanced or metastatic melanoma who have not yet received any prior systemic therapy for their melanoma in this setting.
  2. Arm 2b: Newly diagnosed locally advanced or metastatic NSCLC with a PD-L1 TPS of ≥50% with no known EGFR or ALK positive tumor mutations who have not yet received any prior systemic therapy for their NSCLC (that is, treatment-naive).
  3. Arm 2c: Locally advanced or metastatic melanoma in participants who have not received prior systemic therapy for melanoma in the advanced/metastatic setting.
  4. Arm 2d: Advanced/metastatic melanoma that is CPI refractory and having a centrally confirmed PD-L1 TPS of ≥1% on their Screening tumor biopsy.
* All participants must have measurable disease as determined by RECIST v1.1.
* Participants must have a tumor lesion amenable to biopsy and must provide tumor biopsy sample at baseline (archival formalin-fixed, paraffin-embedded \[FFPE\] tissue collected within 90 days of informed consent is accepted as long as no intervening therapy is received, during this time), and optionally at all on-treatment timepoints (including response or progression) if medically feasible. Participants in Arm 2c: Sufficient tumor tissue (slides or FFPE block) for PD-L1 testing is required as per Laboratory Manual. Participants in Arm 2c may be replaced in this cohort if not PD-L1 evaluable. Participants in Arm 1b melanoma expansion cohort and Arm 2d: Central confirmation of PD-L1 TPS score is required prior to enrollment.
* If the participant is undergoing a new biopsy, they must have another lesion outside of the lesion biopsied at baseline that can be followed as a RECIST v1.1 target lesion 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 

Trial Locations

• The Angeles Clinic and Research Institute, Los Angeles, California, United States
• 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 D.C., 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, St Louis, Missouri, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Melanoma
• Non-Small Cell Lung Cancer (NSCLC)
• Bladder Cancer
• Head and Neck Squamous Cell Carcinoma
• Colorectal Cancer
• Basal Cell Carcinoma
• Triple-Negative Breast Cancer
• Solid Tumors
• Immunotherapy
• Oncology

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