A Phase 1, Open-Label, Multicenter, Dose Escalation Study of mRNA-2752, a Lipid Nanoparticle Encapsulating mRNAs Encoding Human OX40L, IL-23, and IL-36y, 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 participants with relapsed/refractory solid tumor malignancies or lymphoma.

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. Enrollment to Stage 3 of this cohort will include
participants who have previously progressed on prior immune checkpoint blockade
or participants with programmed death-ligand 1 (PD-L1) negative tumor based on
archival tissue (if available).

- 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 and have received 2 or more prior lines of therapy. Participants with
large B-cell lymphoma must have received prior anthracycline containing
chemotherapy.

- 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

- Group 6 Cutaneous melanoma: Must be refractory to immune checkpoint blockade in
the primary or secondary acquired resistance setting.

- Group 7 Non-small cell lung cancer, primary refractory or secondary acquired
resistance to immune checkpoint blockade.

- Dose Exploration:

o Newly diagnosed resectable, BRAF wild-type, Stage IIIB/C/D and Stage IV cutaneous
melanoma with clinically evident lymph node involvement in the neoadjuvant setting.

- 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, with no
deterioration over the previous 2 weeks prior to baseline or day of first dosing.

- 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 and Arm C: Clinical euthyroid status. Participants with clinically
stable hypothyroidism, on adequate thyroid supplementation, are permitted on study.

Exclusion Criteria:

- Has received prior systemic anticancer therapy including investigational agents within
5 half-lives or 28 days of the start of study treatment, whichever is shorter.
Participants enrolled to Arm C may not have received any previous anti-cancer therapy,
immune therapy, radiotherapy, or investigational agents.

- Has received prior radiotherapy within 14 days before the first dose of study
treatment. Participants enrolled to Arm C may not have had prior anticancer therapy
including radiotherapy.

- 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 Medical Monitor.

- Participants with irreversible toxicity not reasonably expected to be exacerbated
by treatment with durvalumab may be included only after consultation with the
Medical Monitor.

- Any 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