Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities
(DLTs) of Sym023, a recombinant, fully human, anti-T-cell immunoglobulin and mucin-domain
containing-3 (anti-TIM-3) monoclonal antibody (mAb). The goal is to establish the maximum
tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of
Sym023 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient
cohorts with locally advanced/unresectable or metastatic solid tumor malignancies or
lymphomas that are refractory to available therapy or for which no standard therapy is
available. If an MTD is not identified, a maximum administered dose (MAD) will be determined.
Sym023 will be given to patients in escalating dose cohorts; each patient will be given one
fixed dose level.

Inclusion Criteria:

- Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.

- Documented (histologically- or cytologically-proven) solid tumor malignancy that is
locally advanced or metastatic; patients with documented lymphomas.

- Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical
intervention due to either medical contraindications or nonresectability of the tumor.

- Refractory to or intolerant of existing therapy(ies) known to provide clinical
benefit.

- Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

- Not of childbearing potential or who agree to use a highly effective method of
contraception during the study beginning within 2 weeks prior to the first dose and
continuing until 6 months after the last dose of study drug.

Exclusion Criteria:

- Women who are pregnant or lactating, or intending to become pregnant before, during,
or within 6 months after the last dose of study drug. Women of childbearing potential
(WOCBP) and fertile men with WOCBP-partner(s) not using and not willing to use a
highly effective method of contraception.

- Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal
cord compression, patients with any of the above not controlled by prior surgery or
radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment
is required.

- Hematologic malignancies other than lymphomas.

- Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism
(PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and
considered stable.

- Active uncontrolled bleeding or a known bleeding diathesis.

- Clinically significant cardiovascular disease or condition.

- Significant ocular disease or condition, including history of autoimmune or
inflammatory disorder.

- Significant pulmonary disease or condition.

- Current or recent (within 6 months) significant gastrointestinal (GI) disease or
condition.

- An active, known, or suspected autoimmune disease, or a documented history of
autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive
medications.

- History of significant toxicities associated with previous administration of immune
checkpoint inhibitors that necessitated permanent discontinuation of that therapy.

- Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic
therapy.

- Inadequate recovery from any prior surgical procedure, or having undergone any major
surgical procedure within 4 weeks prior to C1/D1.

- Known history of human immunodeficiency virus (HIV) or known active infection with
hepatitis B virus (HBV) or hepatitis C virus (HCV).