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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.
  • - 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 programmed death -ligand 1 (PD-1/L1) therapy.
  • - Group 3 Non-Hodgkin's lymphoma: Must have objective evidence of disease progression following an anthracycline containing chemotherapy regimen, as well as an anti-CD20 monoclonal antibody unless CD20 is determined to be negative.
Participants with transformed follicular lymphoma must have received prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to diffuse large B-cell lymphoma (DLBCL)
  • - 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.
  • - 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.
  • - 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: Thyroid-stimulating hormone within normal range.

Exclusion Criteria:

  • - Has received prior systemic anti-cancer therapy including investigational agents within 28 days of the start of study treatment.
  • - Has received prior radiotherapy within 14 days before the first dose of study treatment.
  • - 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 Study Physician.
  • - Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
  • - 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03739931
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

ModernaTX, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

IndustryIndustry
Overall Status Recruiting
Countries Israel, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or Lymphoma, Dose Expansion: Triple Negative Breast Cancer, Head and Neck Squamous Cell Carcinoma, Non-Hodgkin Lymphoma, and Urothelial Cancer
Additional Details

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. 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 visceral lesions may be enrolled into the Dose Confirmation Part to confirm that the dose is also appropriate for this subgroup. Once the MTD/RDE is identified in the Dose Escalation/Dose Confirmation Parts, participants in Arm B will be enrolled into the Dose-Expansion Part in order to assess the preliminary anti-tumor activity of mRNA-2752 in combination with durvalumab. Following completion of 6 cycles of mRNA-2752, participants may continue with durvalumab alone until disease progression, unacceptable toxicity, or 24 months of treatment (total), whichever is sooner. If a participant is experiencing clinical benefit and it is in the participant's best interest, in the opinion of the Investigator, dosing of mRNA-2752 may continue beyond Cycle 6 (up to 24 total months of treatment) after approval from the Sponsor.

Arms & Interventions

Arms

Experimental: Arm A: mRNA-2752

Participants will be administered mRNA-2752 at an applicable dose on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 through 6. The duration for each cycle is 28 days.

Experimental: Arm B: mRNA-2752 + Durvalumab

Participants will be administered mRNA-2752 at an applicable dose on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2 through 6 in combination with durvalumab at a dose based on weight on Day 1 of Cycles 1 through 6. The duration for each cycle is 28 days.

Interventions

Biological: - mRNA-2752

Solution for intratumoral injection

Biological: - Durvalumab

Solution for infusion after dilution

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you. Please note all sites listed may not currently be active in the trial. Please continue to check back for additional site locations.

University of Colorado Denver, Aurora, Colorado

Status

Recruiting

Address

University of Colorado Denver

Aurora, Colorado, 80045

Yale Cancer Center, New Haven, Connecticut

Status

Recruiting

Address

Yale Cancer Center

New Haven, Connecticut, 06510

Sarasota, Florida

Status

Recruiting

Address

Sarah Cannon Research Institute at Florida Cancer Specialists

Sarasota, Florida, 34232

The University of Chicago Medicine, Chicago, Illinois

Status

Not yet recruiting

Address

The University of Chicago Medicine

Chicago, Illinois, 60637

Massachusetts General Hospital, Boston, Massachusetts

Status

Recruiting

Address

Massachusetts General Hospital

Boston, Massachusetts, 02114

Boston, Massachusetts

Status

Recruiting

Address

Cancer Center at Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Henry Ford Hospital, Detroit, Michigan

Status

Recruiting

Address

Henry Ford Hospital

Detroit, Michigan, 48202

Icahn School of Medicine at Mount Sinai, New York, New York

Status

Not yet recruiting

Address

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

James P. Wilmot Cancer Center, Rochester, New York

Status

Not yet recruiting

Address

James P. Wilmot Cancer Center

Rochester, New York, 14642

The Cleveland Clinic Foundation, Cleveland, Ohio

Status

Not yet recruiting

Address

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195

Oregon Health and Science University, Portland, Oregon

Status

Not yet recruiting

Address

Oregon Health and Science University

Portland, Oregon, 97239-3011

Sarah Cannon Research Institute, Nashville, Tennessee

Status

Recruiting

Address

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

International Sites

Rambam Medical Center, Haifa, Israel

Status

Recruiting

Address

Rambam Medical Center

Haifa, , 3109601

Rabin Medical Center, Petah Tikva, Israel

Status

Recruiting

Address

Rabin Medical Center

Petah Tikva, , 4941492

Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel

Status

Recruiting

Address

Tel Aviv Sourasky Medical Center

Tel Aviv-Yafo, , 6423906