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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03261011




Registration number
NCT03261011
Ethics application status
Date submitted
20/08/2017
Date registered
24/08/2017
Date last updated
9/03/2018

Titles & IDs
Public title
Study of the Safety, Pharmacokinetics, and Antitumor Activity of AK104 in Subjects With Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
AK104-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AK-104

Experimental: AK-104 - Single-arm


Other interventions: AK-104
Subjects will receive AK104 by intravenous administration.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
From the time of informed consent signed through 90 days after the last dose of AK104, up to 2 years and 3 months
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
During the first 4 weeks
Secondary outcome [1] 0 0
Objective response rate (ORR) - The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Disease control rate (DCR) - 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.
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Duration of response (DoR) - 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.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Progression-free survival (PFS) - 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.
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Overall survival (OS) - Overall survival is defined as the time from the start of treatment with AK104 until death due to any cause.
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Area under the curve (AUC) of AK104 - The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
Timepoint [6] 0 0
From first dose of AK104 through 90 days after last dose of AK104; Up to 2 years and 3 months.
Secondary outcome [7] 0 0
Maximum observed concentration (Cmax) of AK104 - The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
Timepoint [7] 0 0
From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.
Secondary outcome [8] 0 0
Minimum observed concentration (Cmin) of AK104 at steady state - The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
Timepoint [8] 0 0
From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.
Secondary outcome [9] 0 0
Number of subjects who develop detectable anti-drug antibodies (ADAs) - The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Timepoint [9] 0 0
From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Monash Health - Clayton
Recruitment hospital [2] 0 0
Austin Health - Heidelberg
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Linear Clinical Research/Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Akesobio Australia Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03261011
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Xiaoping Jin, PhD
Address 0 0
Country 0 0
Phone 0 0
+86 (0760) 8987 3999
Fax 0 0
Email 0 0
clinicaltrials@akesobio.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03261011