Safety, Pharmacokinetics (PK), and Efficacy of MK-1308 in Combination With Pembrolizumab in Advanced Solid Tumors (MK-1308-001)

After screening, participants are assigned to either the Dose Escalation Phase or Dose
Confirmation Phase. The Dose Escalation Phase consists of 3 cohorts and will evaluate
available PK and safety data from the first 6 participants of each cohort, including dose
limiting toxicities (DLTs). The purpose of the Dose Confirmation Phase is to gather
additional safety, tolerability, PK, and preliminary efficacy data of MK-1308 in combination
with pembrolizumab. The 5 arms of the Dose Confirmation Phase will include
advanced/metastatic non-small cell lung cancer (NSCLC) and second line advanced/metastatic
small cell lung cancer (SCLC). In participants who have initial evidence of radiological
progressive disease (PD) by modified Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.1, it will be at the discretion of the investigator whether to continue a
participant on study treatment until repeat imaging is obtained.

Protocol Amendment 4 will enroll participants with melanoma in a limited Efficacy Expansion
Cohort. During the Efficacy Expansion Phase, participants will be randomized to receive
either MK-1308 in combination with pembrolizumab or MK-1308 monotherapy.

Inclusion Criteria:

- For Dose Escalation Phase: Have any histologically- or cytologically-confirmed
advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report
and have received, been intolerant to, been ineligible for, or refused all treatment
known to confer clinical benefit

- For Dose Confirmation Phase NSCLC Arms (A, B, C, and E): Have newly diagnosed
histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth
factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed
therapy is not indicated as primary therapy. Participant must not have received prior
systemic treatment for advanced NSCLC or must have received previous neoadjuvant and
adjuvant chemotherapies ≥6 months before dosing of study drug if prior systemic
treatment was given for early stage disease

- For Dose Confirmation Phase SCLC Arm (Arm D): Have histologically- or
cytologically-confirmed metastatic (Stage III/IV) SCLC with progressive disease after
≥1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease
are eligible

- Have measurable disease by RECIST 1.1 as assessed by the local site
investigator/radiology

- Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1

- Female participants of childbearing potential must have negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study treatment
and be willing to use an adequate method of contraception for the course of the study
through 120 days after the last dose of study medication

- Male participants with a female partner(s) of child-bearing potential must be willing
to use an adequate method of contraception for the course of the study through 120
days after the last dose of study medication and refrain from donating sperm during
this period

- Must submit an evaluable baseline tumor sample for analysis (either a recent or
archival tumor sample)

For Efficacy Expansion Phase Arms F and G:

- Have histologically/cytologically-confirmed unresectable Stage III or Stage IV
melanoma per American Joint Committee on Cancer (AJCC) staging system version 8, not
amenable to local therapy

- Have at least 1 measurable lesion by CT or MRI per RECIST 1.1 as confirmed by BICR.
Cutaneous lesions and other superficial lesions are not considered measurable lesions
for the purposes of this protocol, but may be considered as non-target lesions

- Participants with unresectable Stage III or Stage IV disease must have progressed on
treatment with an anti-PD1/L1 monoclonal antibody (mAb) administered either as
monotherapy, or in combination with other checkpoint inhibitors or other therapies
(combinations with anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4] agents
will not be allowed)

- Participants who receive anti-PD-1 therapy as adjuvant treatment following complete
resection of Stage III or IV melanoma and have disease recurrence (unresectable
loco-regional disease or distant metastases) while on active treatment or within 6
months of stopping anti-PD-1

- Have submitted pre-trial imaging and provided a baseline tumor sample

Exclusion Criteria:

- For all phases of the study: Has received previous treatment with another agent
targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4

- For Dose Confirmation phase only: Has received previous treatment with another agent
targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1
(PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or
co-inhibitory T-cell receptor

- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4
weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or
has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or
better from any AEs that were due to cancer therapeutics administered more than 4
weeks earlier

- Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first
dose of study treatment

- Is currently participating and receiving study therapy in a study of an
investigational agent or has participated and received study therapy in a study of an
investigational agent or has used an investigational device within 28 days of
administration of MK-1308.

- Has a history of a second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for 3 years

- For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E) ONLY: Has known
untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis

- Has received any prior immunotherapy and was discontinued from that treatment due to a
Grade 3 or higher immune-related adverse events (irAE)

- Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody
or components of the study drug

- Has any active infection requiring therapy

- Has a history of interstitial lung disease, history of non-infectious pneumonitis that
required steroids (or has current pneumonitis), or history of inflammatory bowel
disease

- Has an active autoimmune disease that has required systemic treatment in the past 2
years

- Has clinically significant cardiac disease

- Has received a live-virus vaccine within 28 days of planned treatment start

- Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis
B or C infections, and/or known to be positive for hepatitis B surface antigen
(HBsAg)/ hepatitis B virus (HBV) DNA

- Has known psychiatric or substance abuse disorders that would interfere with the
participant's ability to cooperate with the requirements of the trial

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with screening and for up to 120 days
following cessation of study medication(s)

- Has not fully recovered from any effects of major surgery without significant
detectable infection

- For Efficacy Expansion Phase Arms (F and G) ONLY: Has known active CNS metastases
and/or carcinomatous meningitis

- Has ocular melanoma

- Has uvular melanoma