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BRIEF TITLE: 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

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


  • Org Study ID: mRNA-2752-P101
  • Secondary ID:
  • NCT ID: NCT03739931
  • NCT Alias:
  • Sponsor: ModernaTX, Inc. - Industry
  • Source: 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.

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.

Overal Status Start Date Phase Study Type
Recruiting November 27, 2018 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Percentage of subjects with dose limiting toxicities (DLTs)

Primary Outcome 1 - Time Frame: Days 1-28

Primary Outcome 2 - Measure: Percentage of subjects with adverse events (AEs)

Primary Outcome 2 - Time Frame: Baseline through 3 months after the last dose of study treatment

Condition:

  • 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

Eligibility

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
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Moderna Clinical Trials

Phone: 855-663-6762

Email: clinicaltrials@modernatx.com

Locations

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