A Study of AK119 (Anti-CD73) in Combination With AK104 in Subjects With Advanced Solid Tumors

NCT04572152 | Completed Phase 1

• 1 other identifier: AK119-102
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 5

Brief Summary

This is a first-in-human (FIH), Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 (Anti-CD73) in Combination with AK104 in Subjects with Advanced or Metastatic Solid Tumors.

Conditions

Advanced or Metastatic Solid Tumors

Keywords

Anti CD73; PD-1/ CTLA-4; Bispecific

Outcome Measures

Primary Outcomes (2)

• Number of participants with 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 90 days after the last dose of study drug

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

  DLTs will be assessed during the first 6 weeks 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 6 weeks of treatment.

  During the first 6 weeks

Secondary Outcomes (5)

• Objective response rate (ORR)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Maximum observed concentration (Cmax) of AK119 and AK104

  From first dose of study drug through 30 days after last dose of study drug

• Minimum observed concentration (Cmin) of AK119 and AK104 at steady state

  From first dose of study drug through 30 days after last dose of study drug

• Number of subjects who develop detectable anti-drug antibodies (ADAs)

  From first dose of study drug through 90 days after last dose of study drug

Study Arms (1)

AK119/ AK104

EXPERIMENTAL

Single-arm

Biological: AK119; Biological: AK104

Interventions

AK119 BIOLOGICAL

Subjects will receive AK119 by intravenous administration.

AK119/ AK104

AK104 BIOLOGICAL

On the same day subjects will receive AK104 by intravenous administration.

AK119/ AK104

Eligibility Criteria

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

You may qualify if:

• Has provided written informed consent
• Age ≥ 18 years.
• In dose-escalation cohorts (Phase 1a), subjects must have histologically or cytologically confirmed advanced or metastatic solid tumor that is refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available, or whereby standard therapy has been refused.
• In pharmacodynamic-confirmation cohorts (Phase 1a), additional enrolled subjects must have histologically or cytologically confirmed selected advanced or metastatic solid tumors, refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available. Other tumor types can be considered after discussion with the Sponsor.
• In dose-expansion cohorts (Phase 1b), subjects with specific tumor types will be enrolled. Subjects must have received no more than three prior lines of systemic therapy (including approved and investigational treatments) for advanced or metastatic disease. Other cohorts of different tumor types may be added based on the emerging pharmacodynamic and anti-tumor response data.
• Subjects must have measurable lesions according to RECIST v1.1. A previously irradiated lesion can be considered a target lesion if the lesion is measurable per RECIST v1.1, and there is objective evidence of interval increase in size since radiotherapy.
• For dose-escalation cohorts (Phase 1a), subjects must have available archived tumor tissue sample (block or a minimum of 10 unstained slides of formalin-fixed paraffin-embedded \[FFPE\] tissues) to allow for correlative biomarker studies.
• For pharmacodynamic-confirmation cohorts (Phase 1a) and dose-expansion cohorts (Phase 1b), subjects must be willing to provide 2 fresh biopsy samples (pre-treatment and on treatment), where clinically appropriate.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to1.
• Adequate organ function
• Life expectancy ≥12 weeks;
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and within 120 days after the last dose of investigational product.
• Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and within 120 days after the last dose of investigational product.

You may not qualify if:

• Receipt of the following treatments or procedures:
• Anticancer small-molecule targeted agent (e.g., tyrosine kinase inhibitor) within 2 weeks prior to the first dose of investigational product;
• Anti-PD-1/PD-L1 mAb within 4 weeks prior to the first dose of investigational product;
• Prior use of approved or investigational anti-CTLA-4 therapy, anti-CD73 therapy or adenosine 2A receptor inhibitors, or any other antibody or drug targeting T cell costimulation or immune checkpoint pathways such as ICOS, or agonists such as CD40, CD137, GITR, OX40 etc.
• Other anticancer mAb within 4 weeks or 5 half-lives (whichever is less) prior to the first dose of investigational product;
• Other anticancer therapy (e.g., chemotherapy, radiotherapy, etc.) within 4 weeks prior to the first dose of investigational product; \[Note: Palliative radiotherapy \> 1 week prior to first dose is allowed\]
• Any major surgery (e.g., laparotomy, thoracotomy, removal of organ\[s\]) within 4 weeks prior to the first dose of investigational product;
• Any other non-approved investigational product or procedure within 4 weeks prior to the first dose of investigational product, or concurrent participation in another therapeutic clinical study;
• Any condition that required systemic treatment with corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of investigational product.
• Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product; Note: seasonal vaccine for influenza which is generally inactivated is allowed.
• Prior organ transplantation;
• Prior malignancy active within the previous 3 years except for the tumor for which a subject is enrolled in the study, and locally curable cancers that have been apparently cured, such as basal cell cancer or carcinoma in situ of the cervix or breast;
• Subjects with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at Screening (based on 2 sets of brain images, performed ≥ 4 weeks apart, and obtained after the brain metastases treatment).
• Active infections (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to the first dose of investigational products. Note: antiviral therapy is permitted for patients with viral hepatitis;
• Known history of human immunodeficiency virus (HIV) infection;

Sponsors & Collaborators

• Akeso: lead

Study Sites (5)

Blacktown Cancer and Haematology Centre (Blacktown Hospital)

Blacktown, New South Wales, 2148, Australia

Location

ICON Cancer Centre

South Brisbane, Queensland, 4101, Australia

Location

Ashford Cancer Centre

Adelaide, South Australia, 5037, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Alfred Health (The Alfred Hospital)

Melbourne, Victoria, 3004, Australia

Location

Study Design

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

Study Record Dates

• First Submitted: September 27, 2020
• First Posted: October 1, 2020
• Study Start: December 7, 2020
• Primary Completion: May 2, 2023
• Study Completion: August 31, 2023
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)