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

• ClinicalTrials.gov Identifier: NCT03261011
• Recruitment Status: Recruiting
• First Posted: August 24, 2017
• Last Update Posted: March 9, 2018
• Sponsor: Akesobio Australia Pty Ltd
• Information provided by (Responsible Party): Akeso ( Akesobio Australia Pty Ltd )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Cancer	Biological: AK-104	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 153 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open-label
• Primary Purpose: Treatment
• Official Title: A Phase 1A/1B Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK104 in Subjects With Advanced Solid Tumors
• Actual Study Start Date: October 3, 2017
• Estimated Primary Completion Date: March 2020
• Estimated Study Completion Date: September 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: AK-104; Single-arm	Biological: AK-104; Subjects will receive AK104 by intravenous administration.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events (AEs) [ Time Frame: From the time of informed consent signed through 90 days after the last dose of AK104, up to 2 years and 3 months ]
   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.
2. Number of participants with a Dose Limiting Toxicity (DLT) [ Time Frame: During the first 4 weeks ]
   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.

Secondary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: Up to 3 years ]
   The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
2. Disease control rate (DCR) [ Time Frame: Up to 3 years ]
   The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
3. Duration of response (DoR) [ Time Frame: Up to 3 years ]
   Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
4. Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
   Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.
5. Overall survival (OS) [ Time Frame: Up to 3 years ]
   Overall survival is defined as the time from the start of treatment with AK104 until death due to any cause.
6. Area under the curve (AUC) of AK104 [ Time Frame: From first dose of AK104 through 90 days after last dose of AK104; Up to 2 years and 3 months. ]
   The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
7. Maximum observed concentration (Cmax) of AK104 [ Time Frame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months. ]
   The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
8. Minimum observed concentration (Cmin) of AK104 at steady state [ Time Frame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months. ]
   The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
9. Number of subjects who develop detectable anti-drug antibodies (ADAs) [ Time Frame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months. ]
   The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• An active infection requiring systemic therapy with the exception of anti-viral therapy for hepatitis as specified by the protocol.
• Receipt of live or attenuated vaccination within 30 days prior to the first dose of AK104.

Contacts and Locations

Contacts

Contact: Xiaoping Jin, PhD; +86 (0760) 8987 3999; clinicaltrials@akesobio.com

Locations

Australia, Victoria

Monash Health; Recruiting

Clayton, Victoria, Australia, 3168

Contact +61 (0) 3 8572 2429

Principal Investigator: Benjamin Markman, MBBS

Austin Health; Recruiting

Heidelberg, Victoria, Australia, 3084

Contact +61 (03) 9496 5354

Principal Investigator: Hui Gan, MBBS

Peter MacCallum Cancer Centre; Recruiting

Melbourne, Victoria, Australia, 3002

Contact +61 (03) 8559 5000

Principal Investigator: Ben Tran, MBBS

Australia, Western Australia

Linear Clinical Research/Sir Charles Gairdner Hospital; Recruiting

Nedlands, Western Australia, Australia, 6009

Contact +61 (0) 8 6382 5100

Principal Investigator: Michael Millward, MBBS

Sponsors and Collaborators

Akesobio Australia Pty Ltd

More Information

• Responsible Party: Akesobio Australia Pty Ltd
• ClinicalTrials.gov Identifier: NCT03261011 History of Changes
• Other Study ID Numbers: AK104-101
• First Posted: August 24, 2017
• Last Update Posted: March 9, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Akeso ( Akesobio Australia Pty Ltd ):

immunotherapy; immuno-oncology; advanced solid tumors