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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03352531




Registration number
NCT03352531
Ethics application status
Date submitted
21/11/2017
Date registered
24/11/2017
Date last updated
21/10/2022

Titles & IDs
Public title
Study of the Safety, Pharmacokinetics, and Antitumor Activity of AK105 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 AK105 in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
AK105-101
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-105

Experimental: AK-105 - Single-arm


Other interventions: AK-105
Anti-PD-1 monoclonal antibody; Subjects will receive AK105 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)
Timepoint [1] 0 0
From the time of informed consent signed through 90 days after the last dose of AK105
Primary outcome [2] 0 0
Number of participants with a Dose Limiting Toxicity (DLT)
Timepoint [2] 0 0
During the first 4 weeks
Secondary outcome [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Disease control rate (DCR)
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Progression-free survival (PFS)
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Area under the curve (AUC) of AK105
Timepoint [5] 0 0
From first dose of AK105 through 30 days after last dose of AK105
Secondary outcome [6] 0 0
Maximum observed concentration (Cmax) of AK105
Timepoint [6] 0 0
From first dose of AK105 through 30 days after last dose of AK105
Secondary outcome [7] 0 0
Minimum observed concentration (Cmin) of AK105 at steady state
Timepoint [7] 0 0
From first dose of AK105 through 30 days after last dose of AK105
Secondary outcome [8] 0 0
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Timepoint [8] 0 0
From first dose of AK105 through to 90 days after last dose of AK105

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.

- 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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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).

- Known active hepatitis B or C infections, or any positive test at screening for
hepatitis B or C virus indicating acute or chronic infection except for subjects with
HCC. Subjects with past or resolved HBV infection are eligible. Subjects positive for
HCV antibody are eligible only if qualitative HCV RNA tests is negative.

- An active infection requiring systemic therapy with the exception of antiviral therapy
for hepatitis as specified by the protocol.

- Receipt of live or attenuated vaccination within 30 days prior to the first dose of
AK105.

- Active or prior documented esophageal or gastric variceal bleeding

- Clinically apparent ascites on physical examination. Ascites that requires active
ongoing paracentesis (within 6 weeks prior to the first scheduled dose) to control
symptoms. Note: ascites detectable on imaging studies only are allowed.

- Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac
involvement of HCC based on imaging.

- Clinically diagnosed hepatic encephalopathy characterized by asterixis.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/12/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2023
Actual
Sample size
Target
108
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
St Vincent's Hospital, Sydney (The Kinghorn Cancer Centre) - Darlinghurst
Recruitment hospital [2] 0 0
Border Medical Oncology - East Albury
Recruitment hospital [3] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 0 0
ICON Cancer Foundation - South Brisbane
Recruitment hospital [5] 0 0
Ashford Cancer Centre Research - Adelaide
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2640 - East Albury
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5037 - Adelaide

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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03352531
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03352531