A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 as Monotherapy or in Combination With AK104

This was a first-in-human, Phase 1 study designed to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK117 as monotherapy or in combination with AK104 in subjects with advanced or metastatic solid tumors.

The study was conducted across 2 parts. Part A of the study was the dose escalation part of AK117 monotherapy as priming dose to evaluate the safety and tolerability of AK117 weekly dosing in solid tumors. Part B which was to evaluate the optimal maintenance dose of AK117 was not performed as the MAD dose level of AK117 monotherapy was determined in Part A.

Part A2 was the dose escalation part of AK117 in combination with AK104 to evaluate the safety and tolerability of AK117 monotherapy in solid tumors.

Eligibility Criteria:
Inclusion Criteria:

1. Able to provide written and signed informed consent
2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
3. Life expectancy ≥12 weeks
4. Females of childbearing potential and non-sterilized males who are sexually active must use an effective method of contraception from screening until 120 days after final dose of investigational product or women of non-childbearing potential.
5. Willing to receive blood transfusion(s) when so advised by the investigator.
6. Adequate organ function.
7. Subjects must have a histologically or cytologically confirmed advanced solid tumor that is refractory or relapsed to the current standard therapies or which no effective standard therapy is available.
8. At least 1 measurable lesion according to RECIST v1.1

Exclusion Criteria:

1. Concurrent enrollment in another clinical study excluding observational trials
2. Prior malignancy active within the previous 3 years except for the tumor for which a subject is enrolled in the study
3. Active brain/central nervous system (CNS) metastases
4. Active infections requiring systemic therapy within 2 weeks prior to the first dose of investigational product.
5. Known history of HIV.
6. Known active hepatitis B or C infections
7. Active or prior documented autoimmune disease that may relapse.
8. History of interstitial lung disease or non-infectious pneumonitis, except those induced by radiation therapies.
9. History of defects in RBC production, or hemoglobin production or metabolism
10. Patients with clinically significant cardio-cerebrovascular disease.
11. History of severe hypersensitivity reactions to other mAbs.
12. History of organ transplantation.
13. Receiving any anticancer therapy targeting the CD47/SIRPα ; Anticancer small molecule targeted agent within 2 weeks prior to the first dose of the investigational product; Anticancer mAbs within 6 weeks prior to the first dose of investigational product or 5 half-lives (whichever is lesser); Other anticancer therapy within 4 weeks prior to the first dose of the investigational product;
14. Subjects with a condition requiring systemic treatment with either corticosteroid (\>10 mg daily doses)) or other immunosuppressive medications within 2 weeks prior to the first dose of investigational product.
15. Received a live attenuated vaccine within 4 weeks prior to the first dose of investigational product.