A study to learn how mRNA 4359 works in the body and how safe it is in participants with advanced solid tumor cancer when administered alone and in combination with pembrolizumab

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Moderna Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Oct 2023 → ongoing

Decision date (initial)

2026-06-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ModernaTX, Inc.

External identifiers

EU CT number

2023-504506-11-00

ClinicalTrials.gov

NCT05533697

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Others, Efficacy, Safety, Pharmacokinetic

For Arm 1, 2a, 2b, 2c: To assess the safety and tolerability of mRNA-4359 administered alone and in combination with pembrolizumab or ipilimumab and nivolumab.
For Arm 2d: To assess the antitumor activity of mRNA-4359 in combination with pembrolizumab.

Secondary objectives 4

1. For Arm 1, 2a, 2b, 2c: To assess the antitumor activity of mRNA-4359 alone and in combination with pembrolizumab or ipilimumab and nivolumab..
2. For Arm 1, 2a, 2b, 2c: To measure and assess T cell profile changes in the tumor after the administration of mRNA-4359 with or without pembrolizumab or ipilimumab and nivolumab..
3. For Arm 2d: To assess the safety and tolerability of mRNA4359 administered in combination with pembrolizumab.
4. For Arm 2d: To evaluate health-related quality of life in participants with locally advanced or metastatic melanoma administered mRNA4359 in combination with pembrolizumab.

Conditions and MedDRA coding

Advanced Solid Tumors

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Dose Escalation (Arm 1a): Participant with locally advanced or metastatic cancer (melanoma, NSCLC, NMIBC, HNSCC, MSS CRC, BCC, or TNBC) who have progressed on or are not eligible for prior standard treatments. Measurable disease and biopsy-accessible lesions are required.
2. Dose Confirmation (Arm 1b): Participants with CPI-refractory advanced melanoma or NSCLC who have progressed following prior standard therapy. Disease must be measurable and biopsy-accessible. For participants in PD Arm Group 2: PD-L1 positivity (≥1%) is required. For NSCLC participants with known actionable mutations (e.g., EGFR, ALK): prior targeted therapy must have been received or declined. For participants in melanoma Arm 1b expansion cohort: must have centrally confirmed PD-L1 expression (≥1%) from a screening biopsy prior to enrollment.
3. Dose Expansion Arms (Arm 2): Participants with locally advanced or metastatic melanoma or NSCLC, with specific biomarker and prior treatment history requirements. For NSCLC, eligibility includes treatment-naïve individuals with PD-L1 TPS ≥50% and no EGFR/ALK alterations. For melanoma, eligibility depends on prior systemic therapy exposure and PD-L1 status, including treatment-naïve and checkpoint inhibitor–refractory cohorts. All participants must have measurable disease per RECIST v1.1 and provide a baseline tumor biopsy. Full eligibility criteria are detailed in the protocol.
4. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
5. Participant has adequate hematological and biological function.

Exclusion criteria 17

1. Participant has active central nervous system tumors or metastases.
2. Participant has received treatment with prohibited medications or investigational agents within 5 half-lives or 14 days prior to the first day of study intervention, whichever is shorter.
3. 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.
4. Participant has any plan to receive a live attenuated vaccine during study treatment or has received a live vaccine within 30 days before the first dose of study treatment.
5. Participant has reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline.
6. Participants capable of becoming pregnant must use highly effective contraception and must not donate eggs during treatment and for a defined period after the last dose. Sexually active male participants must use condoms and refrain from sperm donation during the same period. Specific timelines are detailed in the protocol.
7. Participant has unstable or serious medical conditions (e.g., severe infections, bleeding disorders, GI disease, psychiatric illness) that may compromise their safety, or the protocol compliance are excluded.
8. Participant has concurrent enrollment in another interventional clinical study.
9. Participant with a diagnosis of ocular/uveal melanoma.
10. For Arm 1b melanoma expansion cohort and Arm 2d participants only: Tumor samples must be recent (≤90 days), technically evaluable, and show PD-L1 TPS ≥1% by central testing. Additionally, there must be no intervening systemic therapy from tumor tissue collection date to the start of trial treatment.
11. Participants with Grade >2 neuropathy.
12. Participant has received prior radiotherapy within 14 days prior to the first dose of study treatment. A 7 day washout is permitted for palliative radiation.
13. Participant has a history of severe allergic reactions to any of the study treatment components.
14. Participant has significant heart conditions as defined in the protocol.
15. Participant has a history of other invasive cancers within the past 3 years, unless treated with curative intent and with no evidence of disease.
16. Participants who experienced severe or unresolved adverse events with prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy are excluded. This includes permanent discontinuation due to toxicity, Grade ≥3 immune-related AEs, or neurologic/ocular irAEs of any grade. Full eligibility criteria are detailed in the protocol.
17. Participant has active infections such as tuberculosis, hepatitis B, hepatitis C, or HIV. Participants with well-controlled or resolved infections may be eligible, as defined in the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For Arm 1, 2a, 2b, 2c: Define the MTD and/or RDE of mRNA-4359 (Arm 1a and Arm 1b only), the incidence, nature, and severity of DLTs and AEs, AESIs, and SAEs, including, but not limited to, changes in laboratory results, vital signs, and physical examination after the administration of mRNA-4359 alone and in combination with pembrolizumab or ipilimumab and nivolumab. For Arm 2d: ORR based on BICR per RECIST v1.1 criteria.

Secondary endpoints 4

1. For Arm 1, 2a, 2b, 2c: ORR, DCR, DoR, and PFS based on Investigator Assessment per RECIST v1.1 criteria. For Arm 2d: DoR, DCR, and PFS based on BICR per RECIST v1.1 criteria, and OS based on Investigator assessment.
2. For Arm 1, 2a, 2b, 2c: Change (or % change) from baseline in T cell profile in the tumor.
3. For Arm 2d: The incidence, nature, and severity of AEs, AESIs, and SAEs, after the administration of mRNA-4359 in combination with pembrolizumab.
4. For Arm 2d: Change from baseline in health-related quality of life as measured by FACT-M.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Moderna Inc.

Sponsor organisation

Moderna Inc.

Address

325 Binney Street

City

Cambridge

Postcode

02142-1038

Country

United States

Scientific contact point

Organisation

Moderna Therapeutics Inc.

Contact name

Moderna WeCare Team

Public contact point

Organisation

Moderna Therapeutics Inc.

Contact name

Moderna WeCare Team

Third parties 10

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications