Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects With Resected Solid Tumors and in Combination With Pembrolizumab in Subjects With Unresectable Solid Tumors

Inclusion Criteria:

- Male or female, ≥ 18 years old with the ability to understand and provide signed and
witnessed informed consent, and agree to comply with protocol requirements

- Part A: Subjects must have one of the histologically-confirmed solid malignancies
listed below, must be clinically disease-free at study entry (i.e., subjects in the
adjuvant setting). Subjects will be permitted to complete any standard of care
adjuvant therapy prior to study entry, and those not eligible for any standard of care
adjuvant treatment, or who decline such treatment, are permitted to consent to this
study, as long as all treatment options have been transparently disclosed and
documented in the Subject's medical record

- Part B: Subjects must have one of the histologically- or cytologically-confirmed
unresectable (locally advanced or metastatic) solid malignancies listed below, AND
have measurable disease at study entry defined by RECIST 1.1. AND be considered
suitable for treatment with pembrolizumab; in this study pembrolizumab will be
considered an investigational study drug.

Subjects with any of the following solid malignancies:

a. Non-small cell lung cancer (subjects in Part B must either lack EGFR sensitizing
mutation or ALK translocation per local test results, or must have progressed on approved
standard of care treatment for EGFR or ALK positive NSCLC) b. Small cell lung cancer c.
Melanoma d. Bladder urothelial carcinoma e. Human papillomavirus-negative HNSCC f. Any
solid malignancy known to be MSI high/MMR deficient per local test results, including but
not limited to: CRC, stomach adenocarcinoma, esophageal adenocarcinoma and endometrial
cancer

- Part C: Subjects must have one of the histologically‑ or cytologically confirmed
unresectable (locally advanced or metastatic) solid malignancies listed below, AND
must not have received prior anti‑PD‑1/PD-L1 therapy, AND must have measurable disease
at study entry defined by RECIST 1.1

1. MSS-CRC

2. HPV negative metastatic or recurrent HNSCC of the oral cavity, oropharynx,
hypopharynx, or larynx

3. Bladder urothelial carcinoma

- Part D: Subject must have completed resected adjuvant melanoma and must be clinically
disease-free at study entry (i.e., subjects in the adjuvant setting). Subjects will be
permitted to complete any standard of care adjuvant therapy prior to study entry, and
those not eligible for any standard of care adjuvant treatment, or who decline such
treatment, are permitted to consent to this study, as long as all treatment options
have been transparently disclosed and documented in the subject's medical record

- Parts A and D: subjects must have a FFPE tumor sample available (e.g., from their
prior surgery) that is suitable for the next generation sequencing (NGS) required for
this study.

- Parts B and C: subjects must have at least 1 lesion amenable to the mandatory fresh
tumor biopsy at study entry and provide a biopsy suitable for the NGS required for
this study. An existing (archival) FFPE tumor sample may instead be used for NGS after
discussing with medical monitor

- Subjects must have resolution of toxic effect(s) from prior therapy to Grade 1 or
less. Subjects with ≤ Grade 2 neuropathy or alopecia are an exception to this
criterion. If a subject received major surgery or radiation therapy of > 30 Gy, they
must have recovered from the toxicity and/or complications from the intervention to
Grade 1 or less

- Subject is willing to use an adequate method of contraception for the course of the
study through 120 days after the last dose of study drug (male and female participants
of childbearing potential)

- Subjects with PS of 0 or 1 on the ECOG Performance Scale

- Life expectancy > 12 weeks at Screening

- Subjects with adequate organ and marrow function

- Parts A and D: Subject must consent to required apheresis procedure and meet
additional inclusion criteria per local institutional apheresis procedure

Exclusion Criteria:

- Treatment with any of the following:

1. Any investigational agents, anti-cancer monoclonal antibody, anti-cancer
therapeutic vaccine, immunostimulant (e.g. IL-2) or study drugs from a previous
clinical study within 4 weeks of the first dose of mRNA-4157 or pembrolizumab
(note only a 2 week wash out is required from prior pembrolizumab treatment)

2. Any chemotherapy, targeted small molecule therapy, or radiation therapy within 2
weeks of the first dose of mRNA-4157 or pembrolizumab

3. Live-virus vaccination within 30 days of the first dose of mRNA-4157 or
pembrolizumab. Seasonal flu vaccines that do not contain live virus are permitted

4. Any systemic steroid therapy or other form of immunosuppressive therapy within 7
days of the first dose of mRNA-4157 or pembrolizumab

5. Transfusion of blood products (including platelets or red blood cells[RBCs]) or
administration of colony stimulating factors (including G-CSF, GM-CSF or
recombinant erythropoietin) within 1 week of the NGS blood sample during
screening, and 4 weeks of the first dose of mRNA-4157 or pembrolizumab

- Prior PD-1/PD-L1 treatment is permitted for subjects in Parts A, B and D of this
study, but only subjects who have progressed on their prior PD-1/PD-L1 treatment
without a partial or complete response, and without discontinuing for drug-related
toxicity are eligible

- Active central nervous system metastases and/or carcinomatous meningitis

- Active autoimmune disease that has required systemic treatment in past 2 years

- Has a history of (noninfectious) pneumonitis that required steroids or has current
pneumonitis

- Has a diagnosis of immunodeficiency

- Any clinically-significant cardiac disease defined as New York Heart Association class
III or IV within the past 6 months of Screening, unless, in the opinion of the
Investigator, the disease is well-controlled

- A history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating Investigator

- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial

- Previously identified hypersensitivity to components of the formulations used in this
study

- Had a solid organ or allogeneic bone marrow transplant

- Subjects with a history of interstitial lung disease

- An active infection requiring systemic therapy

- A known history of HIV

- Known active Hepatitis B or Hepatitis C

- Known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin that has undergone curative therapy or in situ cervical cancer

- Subjects participating in apheresis; mandatory in the Part A apheresis expansion phase
cohort and Part D (optional for other study parts), must not meet any of the exclusion
criteria on any day when apheresis is performed, either protocol specific apheresis
criteria, or per local institutional apheresis protocol.