Study of the Safety, Pharmacokinetics, and Antitumor Activity of AK104 in Subjects With Advanced Solid Tumors

NCT03261011 | Completed Phase 1

• 1 other identifier: AK104-101
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 6

Brief Summary

This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK104 as a single agent in adult subjects with advanced solid tumor malignancies. The study consists of a dose escalation phase (Phase 1a) to determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D) for AK104 as a single agent, and a dose expansion phase (Phase 1b) which will characterize treatment of AK104 as a single agent at the MTD or RP2D.

Conditions

Advanced Cancer

Keywords

immunotherapy; immuno-oncology; advanced solid tumors

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 AK104, up to 2 years and 3 months

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

  DLTs will be assessed during the first 4 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 cycle (4 weeks) of treatment.

  During the first 4 weeks

Secondary Outcomes (9)

• Objective response rate (ORR)

  Up to 3 years

• Disease control rate (DCR)

  Up to 3 years

• Duration of response (DoR)

  Up to 3 years

• Progression-free survival (PFS)

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

Study Arms (1)

AK-104

EXPERIMENTAL

Single-arm

Biological: AK-104

Interventions

AK-104 BIOLOGICAL

Subjects will receive AK104 by intravenous administration.

AK-104

Eligibility Criteria

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

You may qualify if:

• Written and signed informed consent and any locally required authorization obtained from the subject/legal representative.
• In dose-escalation cohorts (Phase 1a), histologically or cytologically documented advanced or metastatic solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject refuses standard therapy.
• In the dose-expansion cohorts (Phase 1b), histologically or cytologically confirmed selected advanced solid tumors (to be determined). Subjects must have received no more than three prior lines of systemic therapy for advanced or metastatic disease.
• Subject must have at least one measurable lesion according to RECIST Version1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
• Available archived tumor tissue sample to allow for correlative biomarker studies. In the setting where archival material is unavailable or unsuitable for use, the subject must consent and undergo fresh tumor biopsy.
• Adequate organ function.

You may not qualify if:

• History of severe hypersensitivity reactions to other mAbs.
• Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTL4 antibody or any other antibody or drug targeting T-cell costimulation or checkpoint pathways such as ICOS, or agonists such as CD40, CD137, GITR, OX40 etc.
• Receipt of any immunotherapy, any conventional or investigational systemic anticancer therapy within 4 weeks prior to the first dose of AK104; in the case of mAbs, 6 weeks prior to the first dose of AK104.
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.
• Subjects with a condition requiring systemic treatment with either corticosteroid (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
• Active or prior documented autoimmune disease within the past 2 years.
• Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of organ transplant or hematopoietic stem cell that requires use of immunosuppressives.
• Known allergy or reaction to any component of the AK104 formulation.
• History of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
• Known history of tuberculosis.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection except for subjects with HCC.

Sponsors & Collaborators

• Akesobio Australia Pty Ltd: lead

Study Sites (6)

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Integrated Clinical Oncology Network (ICON)

South Brisbane, Queensland, 4101, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

Linear Clinical Research/Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (2)

• Wang J, Li X, Xiao G, Desai J, Frentzas S, Wang ZM, Xia Y, Li B. CD74 is associated with inflamed tumor immune microenvironment and predicts responsiveness to PD-1/CTLA-4 bispecific antibody in patients with solid tumors. Cancer Immunol Immunother. 2024 Jan 27;73(2):36. doi: 10.1007/s00262-023-03604-2.

  PMID: 38280003 DERIVED

• Frentzas S, Gan HK, Cosman R, Coward J, Tran B, Millward M, Zhou Y, Wang W, Xia D, Wang ZM, Li B, Xia M, Desai J. A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors. Cell Rep Med. 2023 Nov 21;4(11):101242. doi: 10.1016/j.xcrm.2023.101242. Epub 2023 Oct 17.

  PMID: 37852261 DERIVED

Related Links

• Related Info

Study Design

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

Study Record Dates

• First Submitted: August 20, 2017
• First Posted: August 24, 2017
• Study Start: October 3, 2017
• Primary Completion: August 27, 2021
• Study Completion: April 13, 2023
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6)