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.
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.
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
