Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03739931
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : March 25, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
ModernaTX, Inc.

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.

Condition or disease Intervention/treatment Phase
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 Biological: mRNA-2752 Biological: Durvalumab Phase 1

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.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 27, 2018
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : July 31, 2021


Arm Intervention/treatment
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.
Biological: mRNA-2752
Solution for intratumoral injection

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.
Biological: mRNA-2752
Solution for intratumoral injection

Biological: Durvalumab
Solution for infusion after dilution




Primary Outcome Measures :
  1. Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Days 1-28 ]
  2. Number of Participants with Adverse Events (AEs) [ Time Frame: Baseline through 3 months after the last dose of study treatment (duration of study treatment=up to 6 cycles of 28 days) ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR): Number of Participants with Tumor Response (Partial or Complete) [ Time Frame: Baseline through 180 days after the last dose of study treatment (duration of study treatment=up to 6 cycles of 28 days) ]
  2. Protein Expression of IL-23, IL-36γ, and OX40L in Tumors [ Time Frame: Baseline up to Days 2-3 of Cycle 1 and Cycle 3 (each cycle=28 days) ]
  3. Pharmacokinetics: Maximum Observed Concentration (Cmax) [ Time Frame: Predose, immediately after injection, 15 minutes (min), 30 min, 1 hour (hr), 2 hr, 4 hr, 24 hr, and 168 hr postdose of Day 1, Cycle 1; Predose, 4 hr, and 168 hr postdose of Day 1, Cycle 2; Predose of Day 1, Cycle 4; and End of Treatment (cycles=28 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03739931


Contacts
Layout table for location contacts
Contact: Moderna Clinical Trials 877-913-3286 clinicaltrials@modernatx.com

Locations
Layout table for location information
United States, Colorado
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Sarah Cannon Research Institute at Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
United States, Illinois
The University of Chicago Medicine Not yet recruiting
Chicago, Illinois, United States, 60637
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Cancer Center at Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
United States, New York
Icahn School of Medicine at Mount Sinai Not yet recruiting
New York, New York, United States, 10029
James P. Wilmot Cancer Center Not yet recruiting
Rochester, New York, United States, 14642
United States, Ohio
The Cleveland Clinic Foundation Not yet recruiting
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health and Science University Not yet recruiting
Portland, Oregon, United States, 97239-3011
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Israel
Rambam Medical Center Recruiting
Haifa, Israel, 3109601
Rabin Medical Center Recruiting
Petah Tikva, Israel, 4941492
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv-Yafo, Israel, 6423906
Sponsors and Collaborators
ModernaTX, Inc.
AstraZeneca
Layout table for additonal information
Responsible Party: ModernaTX, Inc.
ClinicalTrials.gov Identifier: NCT03739931    
Other Study ID Numbers: mRNA-2752-P101
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: March 25, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ModernaTX, Inc.:
mRNA-2752
OX40L
IL-23
IL-36γ
Intratumoral injection
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Neoplasms
Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Head and Neck Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents