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

January 5, 2023 updated by: Akesobio Australia Pty Ltd

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Sydney, New South Wales, Australia
        • Blacktown Hospital
    • Queensland
      • South Brisbane, Queensland, Australia
        • Icon Cancer Foundation
    • South Australia
      • Kurralta Park, South Australia, Australia
        • Ashford Cancer Centre Research
    • Victoria
      • Heidelberg, Victoria, Australia
        • Austin Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment

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.

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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and nature of adverse events (AEs)
Time Frame: From the time of informed consent signed through 30 days after the last dose of AK117 as monotherapy or in combination with AK104
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)
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: Up to 2 years
ORR defined as the proportion of subjects who achieves a best overall response of CR or PR, assessed by Investigator per RECIST Version 1.1.
Up to 2 years
Disease control rate (DCR)
Time Frame: Up to 2 years
(subjects achieving SD will be included in the DCR if they maintain SD for 16 and 24 weeks respectively).
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
Time Frame: From first dose through to 30 days after last dose of investigational products.
The endpoints for assessment of PK of AK117 and AK104 include serum concentrations of AK117 and AK104 at different timepoints after AK117 and AK104 administration.
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
Time Frame: From first dose through to 30 days after last dose of investigational products.
The immunogenicity of AK117 and AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
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
Time Frame: From first dose through to 30 days after last dose of investigational products.
The endpoints for assessment of PK of AK117 and AK104 include serum concentrations of AK117 and AK104 at different timepoints after AK117 and AK104 administration.
From first dose through to 30 days after last dose of investigational products.
Receptor occupancy (RO) of AK117 as monotherapy or in combination with AK104 to evaluate target engagement
Time Frame: From first dose through to 30 days after last dose of investigational products.
The endpoints will be measured using a flow cytometry-based method on circulating red and white blood cells.
From first dose through to 30 days after last dose of investigational products.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 23, 2020

Primary Completion (Actual)

November 8, 2022

Study Completion (Actual)

November 8, 2022

Study Registration Dates

First Submitted

April 14, 2020

First Submitted That Met QC Criteria

April 14, 2020

First Posted (Actual)

April 16, 2020

Study Record Updates

Last Update Posted (Estimate)

January 9, 2023

Last Update Submitted That Met QC Criteria

January 5, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AK117-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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