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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03739931




Registration number
NCT03739931
Ethics application status
Date submitted
8/11/2018
Date registered
14/11/2018

Titles & IDs
Public title
Dose Escalation Study of mRNA-2752 for Intratumoral Injection to Participants in Advanced Malignancies
Scientific title
A Phase 1, Open-Label, Multicenter, Dose Escalation Study of mRNA-2752, a Lipid Nanoparticle Encapsulating mRNAs Encoding Human OX40L, IL-23, and IL-36?, for Intratumoral Injection Alone and in Combination With Immune Checkpoint Blockade
Secondary ID [1] 0 0
2022-001597-55
Secondary ID [2] 0 0
mRNA-2752-P101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or Lymphoma 0 0
Dose Expansion: Triple Negative Breast Cancer, HNSCC, Non-Hodgkins, Urothelial Cancer, Immune Checkpoint Refractory Melanoma, and NSCLC Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - mRNA-2752
Treatment: Other - Durvalumab

Experimental: Arm A: mRNA-2752 - Participants will be administered mRNA-2752 at an applicable dose as monotherapy.

Experimental: Arm B: mRNA-2752 + Durvalumab - Participants will be administered mRNA-2752 at an applicable dose in combination with durvalumab.

Experimental: Arm C: mRNA-2752 Alone or mRNA-2752 + Durvalumab - Participants will be administered mRNA-2752 at an applicable dose as monotherapy or in combination with durvalumab.


Treatment: Other: mRNA-2752
Solution for intratumoral injection

Treatment: Other: Durvalumab
Solution for infusion after dilution
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to Day 28
Primary outcome [2] 0 0
Number of Participants with Adverse Events (AEs)
Timepoint [2] 0 0
Up to 27 months
Primary outcome [3] 0 0
Arm B: Overall Response Rate (ORR): Percentage of Participants with Tumor Response (Partial or Complete) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) in Cutaneous Melanoma
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [1] 0 0
ORR: Percentage of Participants with Tumor Response (Partial or Complete) Based on RECIST v1.1 and modified RECIST (iRECIST), and Cheson and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) for Participants With Lymphoma
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Pharmacokinetics: Maximum Observed Concentration (Cmax)
Timepoint [2] 0 0
Predose, immediately after injection, and 15 minutes up to 168 hours postdose

Eligibility
Key inclusion criteria
* Written informed consent prior to completing any study-specific procedure
* Histologically confirmed advanced or metastatic disease with at least 1 measurable lesion as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Cheson 2016 criteria
* Dose Escalation/Confirmation:

o Has disease progression after adequate standard of care therapies for metastatic disease that are known to confer clinical benefit, is intolerant to treatment, or refuses standard treatment (no limit to prior lines of therapy)
* Dose Expansion:

* Group 1 Triple negative breast cancer: Must have objective evidence of disease progression during or following at least one prior line of therapy for metastatic or locally advanced disease. Enrollment to Stage 3 of this cohort will include participants who have previously progressed on prior immune checkpoint blockade or participants with programmed death-ligand 1 (PD-L1) negative tumor based on archival tissue (if available).
* Group 2 Head and neck squamous cell carcinoma: Must have objective evidence of disease progression during or following platinum-containing chemotherapy as well as a PD-1/L1 therapy
* Group 3 Non-Hodgkin's lymphoma: Must have objective evidence of disease progression and have received 2 or more prior lines of therapy. Participants with large B-cell lymphoma must have received prior anthracycline containing chemotherapy.
* Group 4 Urothelial cancer, first line: Must be cisplatin ineligible and PD-L1 negative
* Group 5 Urothelial cancer: Must have objective evidence of disease progression during or following platinum-containing chemotherapy
* Group 6 Cutaneous melanoma: Must be refractory to immune checkpoint blockade in the primary or secondary acquired resistance setting.
* Group 7 Non-small cell lung cancer, primary refractory or secondary acquired resistance to immune checkpoint blockade.
* Dose Exploration:

o Newly diagnosed resectable, BRAF wild-type, Stage IIIB/C/D and Stage IV cutaneous melanoma with clinically evident lymph node involvement in the neoadjuvant setting.
* Has a tumor lesion amenable to biopsy and must be willing to provide the baseline and on-treatment tumor biopsy samples if medically feasible. For participants with only 1 lesion amenable to injection, biopsy, and RECIST assessment, that lesion must be =2 centimeters (cm)
* Eastern Cooperative Oncology Group (ECOG) performance status of =1, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
* Has a body weight of >30 kilograms (kg)
* Adequate hematological and biological function
* Has evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal participants
* Treatment Arm B and Arm C: Clinical euthyroid status. Participants with clinically stable hypothyroidism, on adequate thyroid supplementation, are permitted on study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has received prior systemic anticancer therapy including investigational agents within 5 half-lives or 28 days of the start of study treatment, whichever is shorter. Participants enrolled to Arm C may not have received any previous anti-cancer therapy, immune therapy, radiotherapy, or investigational agents.
* Has received prior radiotherapy within 14 days before the first dose of study treatment. Participants enrolled to Arm C may not have had prior anticancer therapy including radiotherapy.
* Has received a live vaccine within 30 days before the first dose of study treatment
* Has current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment
* Have major surgical procedures within 28 days or non-study-related minor procedures within 7 days before the first dose of study treatment.
* Requires active systemic anticoagulation at the time of intratumoral injection or biopsy
* Active central nervous system tumors or metastases
* Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and protocol defined laboratory values

* Participants with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Medical Monitor.
* Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Medical Monitor.
* Any active or prior documented autoimmune or inflammatory disorders
* History of primary immunodeficiency, allogenic solid organ transplantation, or tuberculosis
* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Participants positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
* Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhea, 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
* Has active GI bleeding or hemoptysis or history of bleeding disorder
* Is a female participant who is pregnant or breastfeeding or male or female participant of reproductive potential who are not willing to employ effective birth control from screening to 120 days after the last dose of study treatment

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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/03/2026
Actual
Sample size
Target
Accrual to date
Final
134
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
One Clinical Research Perth - Nedlands
Recruitment hospital [2] 0 0
Alfred Health - Melbourne
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Melanoma Institute of Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
- Wollstonecraft
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
Connecticut
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
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
Israel
State/province [12] 0 0
Haifa
Country [13] 0 0
Israel
State/province [13] 0 0
Petah Tikva
Country [14] 0 0
Israel
State/province [14] 0 0
Ramat Gan
Country [15] 0 0
Israel
State/province [15] 0 0
Tel Aviv-Yafo

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ModernaTX, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03739931