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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05533697




Registration number
NCT05533697
Ethics application status
Date submitted
23/08/2022
Date registered
9/09/2022
Date last updated
26/04/2024

Titles & IDs
Public title
Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors
Scientific title
Phase 1/2 Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors
Secondary ID [1] 0 0
2023-504506-11-00
Secondary ID [2] 0 0
mRNA-4359-P101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - mRNA-4359
Other interventions - Pembrolizumab

Experimental: Arm 1a (Dose Escalation): mRNA-4359 Alone - Participants will be administered mRNA-4359 at an applicable dose as monotherapy.

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.

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.


Other interventions: mRNA-4359
Intramuscular Injection

Other interventions: Pembrolizumab
Intravenous infusion
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Days 1-21 (Cycle 1)
Primary outcome [2] 0 0
Number of Participants with Adverse Events (AEs), AE of Special Interest (AESIs), and Serious AEs (SAEs)
Timepoint [2] 0 0
Up to 34 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Timepoint [1] 0 0
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 outcome [2] 0 0
Disease Control Rate (DCR) Based on RECIST v1.1
Timepoint [2] 0 0
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 outcome [3] 0 0
Duration of Response (DOR) Based on RECIST v1.1
Timepoint [3] 0 0
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 outcome [4] 0 0
Progression Free Survival (PFS) Based on RECIST v1.1
Timepoint [4] 0 0
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 outcome [5] 0 0
Percent Change from Baseline in T Cell Profile in the Periphery and in the Tumor
Timepoint [5] 0 0
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

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/12/2027
Actual
Sample size
Target
194
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Southside Cancer Center - Miranda
Recruitment hospital [2] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment hospital [3] 0 0
Austin Hospital - Melbourne
Recruitment hospital [4] 0 0
One Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2228 - Miranda
Recruitment postcode(s) [2] 0 0
2065 - Wollstonecraft
Recruitment postcode(s) [3] 0 0
3084 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Scotland
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Birmingham
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Oxford
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ModernaTX, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05533697
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Moderna Clinical Trials Support Center
Address 0 0
Country 0 0
Phone 0 0
1-877-777-7187
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05533697