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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05533697
• Other study ID #: mRNA-4359-P101
• Secondary ID: 2023-504506-11-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 18, 2022
• Est. completion date: December 8, 2027

Study information

• Verified date: April 2024
• Source: ModernaTX, Inc.
• Contact: Moderna Clinical Trials Support Center
• Phone: 1-877-777-7187
• Email: clinicaltrials[@]modernatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 194
• Est. completion date: December 8, 2027
• Est. primary completion date: December 8, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Biological:
• mRNA-4359
Intramuscular Injection
• Pembrolizumab
Intravenous infusion

Locations

Country	Name	City	State
Australia	Austin Hospital	Melbourne	Victoria
Australia	Southside Cancer Center	Miranda	New South Wales
Australia	One Clinical Research	Nedlands	Western Australia
Australia	Melanoma Institute Australia	Wollstonecraft	New South Wales
Spain	NEXT Oncology Barcelona	Barcelona
Spain	NEXT Oncology Madrid	Madrid
Spain	NEXT Oncology	Pozuelo de Alarcón	Madrid
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust	London
United Kingdom	Imperial College London	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	Churchill Hospital	Oxford
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Chicago Medicine	Chicago	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Sara Cannon Research Institute Tennessee	Nashville	Tennessee
United States	Orlando Health UF Health Cancer Center	Orlando	Florida
United States	Oregon Health Sciences University	Portland	Oregon
United States	Washington University	Saint Louis	Missouri
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
ModernaTX, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose Limiting Toxicities (DLTs)		Days 1-21 (Cycle 1)
Primary	Number of Participants with Adverse Events (AEs), AE of Special Interest (AESIs), and Serious AEs (SAEs)		Up to 34 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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