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

NCT04349969 | Completed Phase 1

• 1 other identifier: AK117-101
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 4

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.

Conditions

Neoplasms Malignant

Keywords

Antineoplastic Agents, Immunological

Outcome Measures

Primary Outcomes (2)

• Incidence and nature of adverse events (AEs)

  An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.

  From the time of informed consent signed through 30 days after the last dose of AK117 as monotherapy or in combination with AK104

• Number of participants with a Dose Limiting Toxicity (DLT)

  DLTs will be assessed during the first 4 weeks (AK117 monotherapy) or first 3 weeks (AK117+AK104 combination therapy) of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment.

  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 (6)

• Objective response rate (ORR)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• 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

  From first dose through to 30 days after last dose of investigational products.

• Number of subjects who develop detectable anti-drug antibodies (ADAs) of AK117 as monotherapy or in combination with AK104

  From first dose through to 30 days after last dose of investigational products.

• Area under the curve (AUC) of AK117 as monotherapy or in combination with AK104 for assessment of pharmacokinetics

  From first dose through to 30 days after last dose of investigational products.

Study Arms (1)

Treatment

EXPERIMENTAL

Parts A and B: AK117 monotherapy intravenous (IV) infusion- weekly doses in a 28-day cycle. Parts A2: AK117 (QW) + AK104 (Q3W) combination therapy intravenous (IV) infusion in a 21-day cycle.

Drug: AK117; Drug: AK117+AK104

Interventions

AK117 DRUG

All subjects will receive 4 weekly infusions (Days 1, 8, 15, and 22) of AK117 in each 28-day treatment cycle until unacceptable toxicity, documentation of confirmed progressive disease (PD), or subject withdrawal.

Treatment

AK117+AK104 DRUG

All Subjects will receive 3 weekly infusions of AK117 (Days 1, 8, and 15) and 1 infusion of AK104 (on Day 1) as combination therapy in each 21-day treatment cycle until unacceptable toxicity, documentation of confirmed PD, or subject withdrawal.

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written and signed informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
• Life expectancy ≥12 weeks
• 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.
• Willing to receive blood transfusion(s) when so advised by the investigator.
• Adequate organ function.
• 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.
• At least 1 measurable lesion according to RECIST v1.1

You may not qualify if:

• Concurrent enrollment in another clinical study excluding observational trials
• Prior malignancy active within the previous 3 years except for the tumor for which a subject is enrolled in the study
• Active brain/central nervous system (CNS) metastases
• Active infections requiring systemic therapy within 2 weeks prior to the first dose of investigational product.
• Known history of HIV.
• Known active hepatitis B or C infections
• Active or prior documented autoimmune disease that may relapse.
• History of interstitial lung disease or non-infectious pneumonitis, except those induced by radiation therapies.
• History of defects in RBC production, or hemoglobin production or metabolism
• Patients with clinically significant cardio-cerebrovascular disease.
• History of severe hypersensitivity reactions to other mAbs.
• History of organ transplantation.
• 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;
• 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.
• Received a live attenuated vaccine within 4 weeks prior to the first dose of investigational product.

Sponsors & Collaborators

• Akesobio Australia Pty Ltd: lead

Study Sites (4)

Blacktown Hospital

Sydney, New South Wales, Australia

Location

ICON Cancer Foundation

South Brisbane, Queensland, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, Australia

Location

Austin Health

Heidelberg, Victoria, Australia

Location

MeSH Terms

Conditions

Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2020
• First Posted: April 16, 2020
• Study Start: April 23, 2020
• Primary Completion: November 8, 2022
• Study Completion: November 8, 2022
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)