Study of the Safety, Pharmacokinetics, and Antitumor Activity of AK105 in Subjects With Advanced Solid Tumors

NCT03352531 | Completed Phase 1

• 1 other identifier: AK105-101
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 5

Brief Summary

This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK105 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 AK105 as a single agent, and a dose expansion phase (Phase 1b) in subjects with specific tumor types which will characterize treatment of AK105 as a single agent at the MTD or RP2D.

Conditions

Advanced Cancer

Keywords

Anti-PD-1 monoclonal antibody; 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 AK105

• 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 (8)

• Objective response rate (ORR)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Area under the curve (AUC) of AK105

  From first dose of AK105 through 30 days after last dose of AK105

Study Arms (1)

AK-105

EXPERIMENTAL

Single-arm

Biological: AK-105

Interventions

AK-105 BIOLOGICAL

Anti-PD-1 monoclonal antibody; Subjects will receive AK105 by intravenous administration.

AK-105

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.
• 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.
• For dose-escalation phase (Phase 1a), prior exposure to any anti-PD-1, anti-PD-L1, anti-CTL4 antibody. For dose-expansion phase (Phase 1b), 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 AK105.
• Prior treatment with systemic immune modulating agents (other than agents specified above) that was within 28 days prior to enrollment, or within 90 days prior to enrollment if there was an immune related adverse event, or associated with toxicity that resulted in discontinuation of the immune modulating agent.
• 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 AK105 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).

Sponsors & Collaborators

• Akesobio Australia Pty Ltd: lead

Study Sites (5)

St Vincent's Hospital, Sydney (The Kinghorn Cancer Centre)

Darlinghurst, New South Wales, 2010, Australia

Location

Border Medical Oncology

East Albury, New South Wales, 2640, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

ICON Cancer Foundation

South Brisbane, Queensland, 4101, Australia

Location

Ashford Cancer Centre Research

Adelaide, South Australia, 5037, Australia

Location

Related Publications (2)

• Huang Z, Pang X, Zhong T, Qu T, Chen N, Ma S, He X, Xia D, Wang M, Xia M, Li B. Penpulimab, an Fc-Engineered IgG1 Anti-PD-1 Antibody, With Improved Efficacy and Low Incidence of Immune-Related Adverse Events. Front Immunol. 2022 Jun 27;13:924542. doi: 10.3389/fimmu.2022.924542. eCollection 2022.

  PMID: 35833116 DERIVED

• Zheng Y, Mislang ARA, Coward J, Cosman R, Cooper A, Underhill C, Zhu J, Xiong J, Jiang O, Wang H, Xie Y, Zhou Y, Jin X, Li B, Wang ZM, Kwek KY, Xia D, Xia Y, Xu N. Penpulimab, an anti-PD1 IgG1 antibody in the treatment of advanced or metastatic upper gastrointestinal cancers. Cancer Immunol Immunother. 2022 Oct;71(10):2371-2379. doi: 10.1007/s00262-022-03160-1. Epub 2022 Feb 15.

  PMID: 35165764 DERIVED

Related Links

• Related Info

Study Design

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

Study Record Dates

• First Submitted: November 21, 2017
• First Posted: November 24, 2017
• Study Start: January 2, 2018
• Primary Completion: November 30, 2020
• Study Completion: October 28, 2023
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)