Clinical Trials /

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

NCT03739931

Description:

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.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: mRNA-2752-P101
  • NCT ID: NCT03739931

Conditions

  • 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

Interventions

DrugSynonymsArms
mRNA-2752Arm A: mRNA-2752
mRNA-2752 + durvalumabArm B: mRNA-2752 + duvalumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: mRNA-2752Experimental
  • mRNA-2752
Arm B: mRNA-2752 + duvalumabExperimental
  • mRNA-2752 + durvalumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of subjects with dose limiting toxicities (DLTs)
Time Frame:Days 1-28
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Baseline through 180 days after the last dose of study treatment
Safety Issue:
Description:Percentage of patients with tumor response (partial or complete)
Measure:Protein expression of IL-23, IL-36γ and OX40L in tumors
Time Frame:Baseline through 58 days after initial mRNA-2752 dose
Safety Issue:
Description:
Measure:Concentrations of mRNA-2752 in blood and non-compartmental PK parameters
Time Frame:Pre-dose through 29 days after initial mRNA-2752 dose
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ModernaTX, Inc.

Trial Keywords

  • mRNA-2752
  • OX40L
  • IL-23
  • IL-36γ
  • Intratumoral injection

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