A Study of AK112, a PD-1/VEGF Bispecific Antibody, for Advanced Solid Tumors

Inclusion Criteria:

• Written and signed informed consent and any locally required authorization obtainedfrom the subject/legal representative.

• In dose-escalation cohorts (Phase 1a), histologically or cytologically documentedadvanced or metastatic solid tumor that is refractory/relapsed to standardtherapies, or for which no effective standard therapy is available, or the subjectrefuses standard therapy.

• In the dose-expansion cohorts (Phase 1b), histologically or cytologically confirmedselected advanced solid tumors.

• Subject must have at least one measurable lesion according to RECIST Version1.1.

• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.

• Available archived tumor tissue sample to allow for correlative biomarker studies.If unavailable or unsuitable, the subject must consent and undergo fresh tumorbiopsy.

• Adequate organ function.

• Subjects with central nervous system (CNS) metastases must have been treated, beasymptomatic.

• Females of childbearing potential and non-sterilized males who are sexually activemust use an effective method of contraception from screening until 120 days afterfinal dose of investigational product or women of non child bearing potential.

• Life expectancy ≥12 weeks.

Exclusion Criteria:

• History of severe hypersensitivity reactions to other mAbs.

• Prior malignancy active within the previous 3 years except for the tumor for which asubject is enrolled in the study, and locally curable cancers that have beenapparently cured, (e.g. basal cell skin cancer, or carcinoma in situ of the cervixor breast).

• For subjects enrolled in the dose escalation phase, having received prior anti-PD-1,anti-PD-L1, anti-CTLA-4 or any other immunotherapy or immune-oncology (IO) agentwithin 28 days of commencing treatment with AK112 or experienced a toxicity that ledto permanent discontinuation of prior immunotherapy. All AEs while receiving priorimmunotherapy have not completely resolved or resolved to Grade 1 prior toscreening, required the use of additional immunosuppression other thancorticosteroids

• Receiving any immunotherapy, conventional or investigational systemic anticancertherapy within 4 weeks prior to the first dose

• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancertreatment (hormones use for non-cancer related conditions is acceptable).

• Subjects with clinically significant cardiovascular disease

• Subjects with a condition requiring systemic treatment with either corticosteroid (> 10 mg daily ) or other immunosuppressive medications within 2 weeks of study drugadministration.

• Current or recent use of aspirin (> 325 mg/day) or treatment with dipyramidole,ticlopidine, clopidogrel, and cilostazol.

• Current unstable of full-dose oral or parenteral anticoagulants or thrombolyticagents for > 2 weeks prior to the first dose of AK112

• Active or prior documented autoimmune disease within the past 2 years or conditionsnot expected to recur in the absence of an external trigger)

• Active or prior documented inflammatory bowel disease

• History of primary immunodeficiency.

• History of organ transplant.

• Known allergy or reaction to any component of the AK112 formulation.

• History of interstitial lung disease or non-infectious pneumonitis except for thoseinduced by radiation therapies.

• Unresolved toxicities from prior anticancer therapy, defined as having not resolvedto NCI CTCAE v5.0 Grade 0 or 1

• Major surgical procedure within 30 days prior to the first dose of AK112 or stillrecovering from prior surgery.

• Known history of HIV.

• Known active hepatitis B or C infections. Note: Subjects with HCC and positive HBsAgresult are eligible if the subjects were treated with antiviral therapy and HBVviral load less than 500 IU/mL prior to first dose of AK112.

• An active infection requiring systemic therapy

• Received live attenuated vaccination within 30 days prior to the first dose ofAK112.