The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05533697
Recruitment Status : Recruiting
First Posted : September 9, 2022
Last Update Posted : April 26, 2024
Sponsor:
Information provided by (Responsible Party):
ModernaTX, Inc.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Biological: mRNA-4359 Biological: Pembrolizumab Phase 1 Phase 2

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 194 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors
Actual Study Start Date : August 18, 2022
Estimated Primary Completion Date : December 8, 2027
Estimated Study Completion Date : December 8, 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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: mRNA-4359
Intramuscular Injection

Biological: Pembrolizumab
Intravenous infusion
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: mRNA-4359
Intramuscular Injection

Biological: Pembrolizumab
Intravenous infusion


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: 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 ]
  2. Disease Control Rate (DCR) Based on RECIST v1.1 [ Time Frame: 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 ]
  3. Duration of Response (DOR) Based on RECIST v1.1 [ Time Frame: 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 ]
  4. Progression Free Survival (PFS) Based on RECIST v1.1 [ Time Frame: 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 ]
  5. Percent Change from Baseline in T Cell Profile in the Periphery and in the Tumor [ Time Frame: 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05533697


Contacts
Layout table for location contacts
Contact: Moderna Clinical Trials Support Center 1-877-777-7187 clinicaltrials@modernatx.com

Locations
Show Show 26 study locations
Sponsors and Collaborators
ModernaTX, Inc.
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: ModernaTX, Inc.
ClinicalTrials.gov Identifier: NCT05533697    
Other Study ID Numbers: mRNA-4359-P101
2023-504506-11-00 ( Other Identifier: EU CT Number )
First Posted: September 9, 2022    Key Record Dates
Last Update Posted: April 26, 2024
Last Verified: April 2024

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ModernaTX, Inc.:
Locally advanced
Metastatic
Relapsed or refractory solid tumor malignancies
 Pembrolizumab
Oncology
Solid tumors
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
 Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action