Sym021 Monotherapy and in Combination With Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies or Lymphomas

Part 1 of this study will evaluate the preliminary safety, tolerability, and dose-limiting
toxicities (DLTs) of Sym021, an anti-programmed cell death protein 1 (PD-1) 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 Sym021 when administered once every 2
weeks (Q2W) by 30-minute intravenous (IV) infusion. Sym021 will be given to patients in
escalating dose cohorts; each patient will be given one fixed dose level.

Part 2 of this study will evaluate the safety, tolerability, and DLTs to establish the MTD
and/or RP2D of sequential escalating doses of Sym022 and Sym023 when administered Q2W in
combination with the RP2D of Sym021, each by IV infusion. Dose levels of Sym021+Sym022 and
Sym021+Sym023 will be evaluated until for each combination the MTD is identified, a maximum
administered dose (MAD) is reached, or until a RP2D for the added mAb (Sym022 or Sym023) in
combination with Sym021 is selected. Each patient will be given one fixed dose level of an
assigned combination.

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 lymphoma.

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

- Persons of childbearing potential agreeing 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(s); men agreeing to
refrain from sperm donation during this period.

Exclusion Criteria:

- Women who are pregnant or intending to become pregnant before, during, or within 6
months after the last dose of study drug; women who are breastfeeding; persons of
childbearing potential and not willing to use a highly effective method of
contraception.

- Central nervous system (CNS) malignancies; patients with known, untreated 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 lymphoma.

- 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 an 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 organ transplantation (e.g., stem cell or solid organ transplant).

- 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 except for persistent Grade 2 alopecia, peripheral neuropathy, decreased
hemoglobin, hypomagnesemia, and/or end-organ failure being adequately managed by
hormone replacement 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).

Drugs and Other Treatments Exclusion Criteria:

- Part 2 Combination Dose-Escalations ONLY: Prior therapy with:

- Sym021 or other inhibitors of PD-1/PD-L1.

- Sym022 or other inhibitors of LAG-3, if participating in Arm A.

- Sym023 or other inhibitors of TIM-3, if participating in Arm B.

- Any antineoplastic agent for the primary malignancy (standard or investigational)
without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest,
prior to first study drug administration and during study, with exceptions.

- Any other investigational treatments within 2 weeks prior to and during study;
includes participation in any medical device or supportive care therapeutic
intervention trials.

- Radiotherapy, with exceptions.

- Use of live vaccines against infectious diseases 4 weeks prior to first study drug
administration and during study.

- Immunosuppressive or systemic hormonal therapy within 2 weeks prior to first study
drug administration and during study, with exceptions.

- Prophylactic use of hematopoietic growth factors within 1 week prior to first study
drug administration and during Cycle 1 of study.