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

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

INTRODUCTION

  • Org Study ID: mRNA-2752-P101
  • Secondary ID: N/A
  • NTC ID: NCT03739931
  • Sponsor: 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.

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.

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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of Participants with Dose Limiting Toxicities (DLTs)

Primary Outcome 1 - Timeframe: Days 1-28

Primary Outcome 2 - Measure: Number of Participants with Adverse Events (AEs)

Primary Outcome 2 - Timeframe: Baseline through 3 months after the last dose of study treatment (duration of study treatment=up to 6 cycles of 28 days)

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

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 877-913-3286

Email: clinicaltrials@modernatx.com

LOCATION

Facility Status Contact
Facility: University of Colorado Denver
Aurora, Colorado 80045
United States
Status: Recruiting Contact: N/A
Facility: Yale Cancer Center
New Haven, Connecticut 06510
United States
Status: Recruiting Contact: N/A
Facility: Sarah Cannon Research Institute at Florida Cancer Specialists
Sarasota, Florida 34232
United States
Status: Recruiting Contact: N/A
Facility: Massachusetts General Hospital
Boston, Massachusetts 02114
United States
Status: Recruiting Contact: N/A
Facility: Cancer Center at Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: N/A
Facility: Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: N/A
Facility: Henry Ford Hospital
Detroit, Michigan 48202
United States
Status: Recruiting Contact: N/A
Facility: Sarah Cannon Research Institute
Nashville, Tennessee 37203
United States
Status: Recruiting Contact: N/A
Facility: Rambam Medical Center
Haifa, 3109601
Israel
Status: Recruiting Contact: N/A
Facility: Rabin Medical Center
Petah Tikva, 4941492
Israel
Status: Recruiting Contact: N/A
Facility: Tel Aviv Sourasky Medical Center
Tel Aviv-Yafo, 6423906
Israel
Status: Recruiting Contact: N/A