Trial Title:
Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors
NCT ID:
NCT05533697
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Pembrolizumab
Conditions: Keywords:
Locally advanced
Metastatic
Relapsed or refractory solid tumor malignancies
Pembrolizumab
Oncology
Solid tumors
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
mRNA-4359
Description:
Intramuscular Injection
Arm group label:
Arm 1a (Dose Escalation): mRNA-4359 Alone
Arm group label:
Arm 1b (Dose Confirmation): mRNA-4359 in Combination with Pembrolizumab
Arm group label:
Arm 2 (Dose Expansion): mRNA-4359 in Combination with Pembrolizumab
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Intravenous infusion
Arm group label:
Arm 1b (Dose Confirmation): mRNA-4359 in Combination with Pembrolizumab
Arm group label:
Arm 2 (Dose Expansion): mRNA-4359 in Combination with Pembrolizumab
Summary:
The primary goal of this study is to assess the safety and tolerability of mRNA-4359
administered alone and in combination with pembrolizumab.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCSF Helen Diller Family Comprehensive Cancer Center
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Colorado Cancer Center
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Facility:
Name:
George Washington University
Address:
City:
Washington
Zip:
20037
Country:
United States
Status:
Recruiting
Facility:
Name:
Orlando Health UF Health Cancer Center
Address:
City:
Orlando
Zip:
32806
Country:
United States
Status:
Recruiting
Facility:
Name:
The University of Chicago Medicine
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Facility:
Name:
Henry Ford Hospital
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Recruiting
Facility:
Name:
Washington University
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Facility:
Name:
John Theurer Cancer Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Facility:
Name:
Carolina BioOncology Institute
Address:
City:
Huntersville
Zip:
28078
Country:
United States
Status:
Completed
Facility:
Name:
Oregon Health Sciences University
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Facility:
Name:
Sara Cannon Research Institute Tennessee
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Facility:
Name:
Southside Cancer Center
Address:
City:
Miranda
Zip:
2228
Country:
Australia
Status:
Recruiting
Facility:
Name:
Melanoma Institute Australia
Address:
City:
Wollstonecraft
Zip:
2065
Country:
Australia
Status:
Recruiting
Facility:
Name:
Austin Hospital
Address:
City:
Melbourne
Zip:
3084
Country:
Australia
Status:
Recruiting
Facility:
Name:
One Clinical Research
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Status:
Recruiting
Facility:
Name:
NEXT Oncology
Address:
City:
Pozuelo de Alarcón
Zip:
28223
Country:
Spain
Status:
Recruiting
Facility:
Name:
NEXT Oncology Barcelona
Address:
City:
Barcelona
Zip:
08023
Country:
Spain
Status:
Recruiting
Facility:
Name:
NEXT Oncology Madrid
Address:
City:
Madrid
Zip:
28223
Country:
Spain
Status:
Recruiting
Facility:
Name:
Beatson West of Scotland Cancer Centre
Address:
City:
Glasgow
Zip:
G12 0YN
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Queen Elizabeth Hospital Birmingham
Address:
City:
Birmingham
Zip:
B15 2GW
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
University College London Hospitals NHS Foundation Trust
Address:
City:
London
Zip:
NW1 2PG
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Guy's and St. Thomas' NHS Foundation Trust
Address:
City:
London
Zip:
SE1 7EH
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Imperial College London
Address:
City:
London
Zip:
W12 0HS
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Churchill Hospital
Address:
City:
Oxford
Zip:
OX3 7LE
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
University Hospital Southampton NHS Foundation Trust
Address:
City:
Southampton
Zip:
SO16 6YD
Country:
United Kingdom
Status:
Recruiting
Start date:
August 18, 2022
Completion date:
December 8, 2027
Lead sponsor:
Agency:
ModernaTX, Inc.
Agency class:
Industry
Source:
ModernaTX, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05533697
