Clinical trial NCT04349969: A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 as Monotherapy or in Combination With AK104
Official title: A Phase 1 Multicenter, Open Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 as Monotherapy or in Combination With AK104 in Subjects With Relapsed/Refractory Advanced or Metastatic Solid Tumors or Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms Malignant
Keywords: Antineoplastic Agents, Immunological
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2020-04-16
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Primary outcomes:
measure: Incidence and nature of adverse events (AEs)
timeFrame: From the time of informed consent signed through 30 days after the last dose of AK117 as monotherapy or in combination with AK104
measure: Number of participants with a Dose Limiting Toxicity (DLT)
timeFrame: During the first 4 weeks of first treatment dose of AK117 as monotherapy or during the first 3 weeks of treatment dose of AK117+AK104 as combination therapy.
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Maximum observed concentration (Cmax) of AK117 as monotherapy or in combination with AK104 and Minimum observed concentration (Cmin) of AK117 at steady stateconcentration (Cmin) of AK117 at steady state
timeFrame: From first dose through to 30 days after last dose of investigational products.
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs) of AK117 as monotherapy or in combination with AK104
timeFrame: From first dose through to 30 days after last dose of investigational products.
measure: Area under the curve (AUC) of AK117 as monotherapy or in combination with AK104 for assessment of pharmacokinetics
timeFrame: From first dose through to 30 days after last dose of investigational products.
measure: Receptor occupancy (RO) of AK117 as monotherapy or in combination with AK104 to evaluate target engagement
timeFrame: From first dose through to 30 days after last dose of investigational products.
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: ICON Cancer Foundation
state: Queensland
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
Study officials:
References: