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
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.
18 Years and up
Accepting Healthy Volunteers?
- 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
- 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