Dose Escalation Study of mRNA-2752 for Intratumoral Injection to Participants in Advanced Malignancies

NCT03739931 | Completed Phase 1 FDA Drug

• 2 other identifiers: mRNA-2752-P1012022-001597-55
• Study Type: interventional
• Target: 134
• Locations: 3 countries
• Sites: 24

Brief Summary

The clinical study will assess the safety and tolerability of escalating intratumoral doses of mRNA-2752 in participants with relapsed/refractory solid tumor malignancies or lymphoma.

Conditions

Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or Lymphoma; Dose Expansion: Triple Negative Breast Cancer, HNSCC, Non-Hodgkins, Urothelial Cancer, Immune Checkpoint Refractory Melanoma, and NSCLC Lymphoma

Keywords

mRNA-2752; OX40L; IL-23; IL-36γ; Intratumoral injection

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Dose Limiting Toxicities (DLTs)

  Up to Day 28

• Number of Participants with Adverse Events (AEs)

  Up to 27 months

• 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

  Up to 2 years

Secondary Outcomes (2)

• 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

  Up to 2 years

• Pharmacokinetics: Maximum Observed Concentration (Cmax)

  Predose, immediately after injection, and 15 minutes up to 168 hours postdose

Study Arms (3)

Arm A: mRNA-2752

EXPERIMENTAL

Participants will be administered mRNA-2752 at an applicable dose as monotherapy.

Biological: mRNA-2752

Arm B: mRNA-2752 + Durvalumab

EXPERIMENTAL

Participants will be administered mRNA-2752 at an applicable dose in combination with durvalumab.

Biological: mRNA-2752; Biological: Durvalumab

Arm C: mRNA-2752 Alone or mRNA-2752 + Durvalumab

EXPERIMENTAL

Participants will be administered mRNA-2752 at an applicable dose as monotherapy or in combination with durvalumab.

Biological: mRNA-2752; Biological: Durvalumab

Interventions

mRNA-2752 BIOLOGICAL

Solution for intratumoral injection

Arm A: mRNA-2752; Arm B: mRNA-2752 + Durvalumab; Arm C: mRNA-2752 Alone or mRNA-2752 + Durvalumab

Durvalumab BIOLOGICAL

Solution for infusion after dilution

Arm B: mRNA-2752 + Durvalumab; Arm C: mRNA-2752 Alone or mRNA-2752 + Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• ModernaTX, Inc.: lead
• AstraZeneca: collaborator

Study Sites (24)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

Providence St. John's Health Center

Santa Monica, California, 90404, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Sarah Cannon Research Institute at Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

The University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Cancer Center at Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

James P. Wilmot Cancer Center

Rochester, New York, 14642, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239-3011, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

One Clinical Research Perth

Nedlands, Western Australia, 6009, Australia

Location

Alfred Health

Melbourne, 3004, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Melanoma Institute of Australia

Wollstonecraft, Australia

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5224213, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Related Publications (1)

• Srikrishna D, Sachsenmeier K. We need to bring R0 < 1 to treat cancer too. Genome Med. 2021 Jul 26;13(1):120. doi: 10.1186/s13073-021-00940-9.

  PMID: 34311780 DERIVED

MeSH Terms

Conditions

Lymphoma; Squamous Cell Carcinoma of Head and Neck

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms by Site

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 14, 2018
• Study Start: November 27, 2018
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); IL (4); US (16)