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.
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.
- 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
- 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
- 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
- Active or prior documented autoimmune or inflammatory disorders
- History of primary immunodeficiency, allogenic solid organ transplantation, or
- 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