Dose Escalation and Efficacy Study of mRNA 2416 for Intratumoral Injection to Patients With Advanced Malignancies

This is a first-in-human, Phase 1, open-label, multicenter, dose escalation and efficacy
study designed to determine the safety and tolerability of repeated intratumoral injections
of mRNA 2416 in patients with advanced relapsed/refractory solid tumor malignancies or
lymphoma and to assess the ORR of mRNA-2416 monotherapy in ovarian cancer based on RECIST
v1.1. The study will include 3 dosing periods: a Dose Escalation period in non-visceral
lesions followed by a Dose Confirmation period in visceral lesions and an Expansion period at
the MTD/RDE as determined by the Dose Escalation period.

Inclusion Criteria:

- Written informed consent prior to completing any study-specific procedure

- Dose Escalation period: histologically- or cytologically-confirmed advanced/metastatic
solid tumor or lymphoma by pathology report and who has received, or been intolerant
to, all approved therapies

- Dose Confirmation and Expansion periods: Histologically or cytologically confirmed
diagnosis of: epithelial cancer of the ovary, fallopian tube, or peritoneum which is
platinum resistant or platinum refractory. Patients must have received at least 2
prior lines of therapy. Patients with known BRCA mutation positive must have been
treated with and progressed on at least 1 prior PARPi (poly(ADP-ribose) polymerase
inhibitor)

- All lesion(s) targeted for the initial injection must be ≥ 0.5 cm on longest diameter,
be at least 5 mm thick, and have distinct borders based on exam or imaging, not close
to critical structures such as major vessels, nerves, or airways

- Patients must have measurable disease as determined by RECIST v1.1 (solid tumors) or
Cheson 2014 criteria (lymphomas)

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

- Adequate hematological and biological function

- Female patients of childbearing potential must have a negative serum pregnancy test

- Male and female patients must agree to use a highly reliable method of birth control

Exclusion Criteria:

- Active central nervous system tumors or metastases

- Treatment with chemotherapy, radiation (local radiation for palliative care is
permitted), hormonal anti-cancer treatment, or biologic therapy <14 days prior to the
first day of study treatment (Cycle 1 Day 1 [C1D1]). Treatment with any other
investigational agent or treatment with any anti-cancer monoclonal antibody,
immunostimulant, or vaccine <28 days prior to C1D1

- Reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or
baseline

- Active or prior autoimmune disorder within the past 2 years

- History of primary immunodeficiency, solid organ transplantation, or tuberculosis

- Any plan to receive a live attenuated vaccine during study treatment

- History of human immunodeficiency virus infection (testing is not required)

- Active/chronic hepatitis B or C

- Females who are pregnant or breastfeeding