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

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ClinicalTrials.gov Identifier: NCT03739931
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : October 25, 2019
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 patients 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: mRNA-2752 + 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 patients with histologically confirmed advanced or metastatic solid tumor malignancies or lymphoma. The study consists of 2 dose escalation and dose confirmation parts (Arms A and B) followed by Dose Expansion parts in select indications.

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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 : June 2020
Estimated Study Completion Date : July 2021


Arm Intervention/treatment
Experimental: Arm A: mRNA-2752 Biological: mRNA-2752
mRNA-2752 dose escalation and expansion

Experimental: Arm B: mRNA-2752 + duvalumab Biological: mRNA-2752 + durvalumab
mRNA-2752 + durvalumab dose escalation and expansion




Primary Outcome Measures :
  1. Percentage of subjects with dose limiting toxicities (DLTs) [ Time Frame: Days 1-28 ]
  2. Percentage of subjects with adverse events (AEs) [ Time Frame: Baseline through 3 months after the last dose of study treatment ]

Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Baseline through 180 days after the last dose of study treatment ]
    Percentage of patients with tumor response (partial or complete)

  2. Protein expression of IL-23, IL-36γ and OX40L in tumors [ Time Frame: Baseline through 58 days after initial mRNA-2752 dose ]
  3. Concentrations of mRNA-2752 in blood and non-compartmental PK parameters [ Time Frame: Pre-dose through 29 days after initial mRNA-2752 dose ]


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.


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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 RECIST v1.1 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 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. Patients 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 patients with only 1 lesion amenable to injection, biopsy, and RECIST assessment, that lesion must be ≥ 2 cm
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
  • Has a body weight of > 30 kg
  • Adequate hematological and biological function
  • Has evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
  • 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 current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment.
  • Active central nervous system tumors or metastases
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and protocol defined laboratory values

    • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
    • Patients 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). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, 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 patient to give written informed consent
  • Has active GI bleeding or hemoptysis or history of bleeding disorder
  • Is a female patient who is pregnant or breastfeeding or male or female patient 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
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Contact: Moderna Clinical Trials 855-663-6762 clinicaltrials@modernatx.com

Locations
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United States, Colorado
University of Colorado Aurora Recruiting
Aurora, Colorado, United States, 80045
Contact: Kristen Califano, RN, BSN, OCN    720-848-0592    Kristen.Califano@ucdenver.edu   
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: Ingrid Palma, MHS    203-737-5342    ingrid.palma@yale.edu   
United States, Florida
Sarah Cannon Research Institute at Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Jill Martin, RN    941-377-9993    Jill.Martin@flcancer.com   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Dan McLoughlin    617-724-3089    DEMCLOUGHLIN@MGH.HARVARD.EDU   
Cancer Center at Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Emanuelle Andrianopoulos    617-975-7404    eandrian@bidmc.harvard.edu   
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Matthew Milstein    617-632-6627      
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Karie Gignac, RN, OCN, CHPCN    313-916-7453    Kgignac1@hfhs.org   
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Nikhil Ramaprasad, MS    615-329-7423    Nikhil.Ramaprasad@SarahCannon.com   
Israel
Rabin Medical Center Recruiting
Petah Tikva, Israel, 4941492
Contact: Michael Cohavi    972-3-9378077    shmichalco1@clalit.org.il   
Sponsors and Collaborators
ModernaTX, Inc.
AstraZeneca

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Responsible Party: ModernaTX, Inc.
ClinicalTrials.gov Identifier: NCT03739931     History of Changes
Other Study ID Numbers: mRNA-2752-P101
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: October 25, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Lymphoma
Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of 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
Head and Neck Neoplasms
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents