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Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or LymphomaPhase 1NCT03739931

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

A Phase 1 study testing mRNA-2752 and Durvalumab in people with Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or Lymphoma and Dose Expansion: Triple Negative Breast Cancer, HNSCC, Non-Hodgkins, Urothelial Cancer, Immune Checkpoint Refractory Melanoma, and NSCLC Lymphoma, run by ModernaTX, Inc. at 24 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
mRNA-2752 and Durvalumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
134 participants
Where
24 sitesin 3 countries
Study dates
27 Nov 2018to 1 Aug 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

24 sites in 3 countries.

24 sites in 3 countries

United States16 sites
  • University of Colorado Denver

    Aurora, Colorado, 80045

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Cancer Center at Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • The University of Chicago Medicine

    Chicago, Illinois, 60637

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Yale Cancer Center

    New Haven, Connecticut, 06510

  • NYU Langone Medical Center

    New York, New York, 10016

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Oregon Health and Science University

    Portland, Oregon, 97239-3011

  • James P. Wilmot Cancer Center

    Rochester, New York, 14642

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94143

  • Providence St. John's Health Center

    Santa Monica, California, 90404

  • Sarah Cannon Research Institute at Florida Cancer Specialists

    Sarasota, Florida, 34232

Other trials in United States

Australia4 sites
  • Alfred Health

    Melbourne, 3004

  • One Clinical Research Perth

    Nedlands, Western Australia, 6009

  • Westmead Hospital

    Westmead, 2145

  • Melanoma Institute of Australia

    Wollstonecraft

Other trials in Australia

Israel4 sites
  • Rambam Medical Center

    Haifa, 3109601

  • Rabin Medical Center

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center

    Ramat Gan, 5224213

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 6423906

Other trials in Israel

About this study

Official 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-36γ, for Intratumoral Injection Alone and in Combination With Immune Checkpoint Blockade

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.

Read the detailed description

This is a Phase 1, open-label, multicenter, dose-escalation study of intratumoral injections of mRNA-2752 alone and in combination with intravenously administered immune checkpoint blockade therapy in participants with histologically confirmed advanced or metastatic solid tumor malignancies or lymphoma. The study consists of Dose Escalation and Dose Confirmation Parts, which will occur in Arm A and Arm B, followed by a Dose Expansion Part, which will occur in Arm B, and a Dose Exploration in Arm C as a neoadjuvant therapy for cutaneous melanoma.

Participants in Arm A and in Arm B will be enrolled into the Dose Escalation Part and the doses of mRNA-2752 will be administered in a dose escalation regimen until a maximum tolerated dose (MTD) or a recommended dose for expansion (RDE) is identified. When the MTD/RDE is identified, participants with solid tumors or lymphoma with visceral lesions may be enrolled into the Dose Confirmation Part to confirm that the dose is also appropriate for this subgroup.

Being tested
mRNA-2752, Durvalumab
Keywords
mRNA-2752, OX40L, IL-23, IL-36γ, Intratumoral injection
Medical subject headings
Lymphoma, Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • mRNA-2752Biological

    Solution for intratumoral injection

  • DurvalumabBiological

    Solution for infusion after dilution

Study groups in NCT03739931
Study groupRoleWhat they receive
Arm A: mRNA-2752ExperimentalParticipants will be administered mRNA-2752 at an applicable dose as monotherapy.
Receives: Biological: mRNA-2752
Arm B: mRNA-2752 + DurvalumabExperimentalParticipants will be administered mRNA-2752 at an applicable dose in combination with durvalumab.
Receives: Biological: mRNA-2752; Biological: Durvalumab
Arm C: mRNA-2752 Alone or mRNA-2752 + DurvalumabExperimentalParticipants will be administered mRNA-2752 at an applicable dose as monotherapy or in combination with durvalumab.
Receives: Biological: mRNA-2752; Biological: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with Dose Limiting Toxicities (DLTs)

    Measured: Up to Day 28

  2. Number of Participants with Adverse Events (AEs)

    Measured: Up to 27 months

  3. 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

    Measured: Up to 2 years

Secondary outcomes (2)
  1. 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

    Measured: Up to 2 years

  2. Pharmacokinetics: Maximum Observed Concentration (Cmax)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2018
  2. Study start27 Nov 2018
  3. Primary completion1 Aug 2025
  4. Study completion1 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03739931
Sponsor's protocol ID
mRNA-2752-P101
Other IDs
2022-001597-55
Status last verified
Aug 2025
First submitted
8 Nov 2018
Last updated
15 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34311780

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing mRNA-2752 and Durvalumab in people with Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or Lymphoma and Dose Expansion: Triple Negative Breast Cancer, HNSCC, Non-Hodgkins, Urothelial Cancer, Immune Checkpoint Refractory Melanoma, and NSCLC Lymphoma, run by ModernaTX, Inc. at 24 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Australia, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Dose Limiting Toxicities (DLTs) (time frame: Up to Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03739931, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2025.

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