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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/NCT04349969




Registration number
NCT04349969
Ethics application status
Date submitted
14/04/2020
Date registered
16/04/2020
Date last updated
9/01/2023

Titles & IDs
Public title
A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 as Monotherapy or in Combination With AK104
Scientific title
A Phase 1 Multicenter, Open Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 as Monotherapy or in Combination With AK104 in Subjects With Relapsed/Refractory Advanced or Metastatic Solid Tumors or Lymphomas
Secondary ID [1] 0 0
AK117-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms Malignant 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AK117
Treatment: Drugs - AK117+AK104

Experimental: Treatment - Parts A and B: AK117 monotherapy intravenous (IV) infusion- weekly doses in a 28-day cycle.
Parts A2: AK117 (QW) + AK104 (Q3W) combination therapy intravenous (IV) infusion in a 21-day cycle.


Treatment: Drugs: AK117
All subjects will receive 4 weekly infusions (Days 1, 8, 15, and 22) of AK117 in each 28-day treatment cycle until unacceptable toxicity, documentation of confirmed progressive disease (PD), or subject withdrawal.

Treatment: Drugs: AK117+AK104
All Subjects will receive 3 weekly infusions of AK117 (Days 1, 8, and 15) and 1 infusion of AK104 (on Day 1) as combination therapy in each 21-day treatment cycle until unacceptable toxicity, documentation of confirmed PD, or subject withdrawal.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and nature of adverse events (AEs)
Timepoint [1] 0 0
From the time of informed consent signed through 30 days after the last dose of AK117 as monotherapy or in combination with AK104
Primary outcome [2] 0 0
Number of participants with a Dose Limiting Toxicity (DLT)
Timepoint [2] 0 0
During the first 4 weeks of first treatment dose of AK117 as monotherapy or during the first 3 weeks of treatment dose of AK117+AK104 as combination therapy.
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
Maximum observed concentration (Cmax) of AK117 as monotherapy or in combination with AK104 and Minimum observed concentration (Cmin) of AK117 at steady stateconcentration (Cmin) of AK117 at steady state
Timepoint [3] 0 0
From first dose through to 30 days after last dose of investigational products.
Secondary outcome [4] 0 0
Number of subjects who develop detectable anti-drug antibodies (ADAs) of AK117 as monotherapy or in combination with AK104
Timepoint [4] 0 0
From first dose through to 30 days after last dose of investigational products.
Secondary outcome [5] 0 0
Area under the curve (AUC) of AK117 as monotherapy or in combination with AK104 for assessment of pharmacokinetics
Timepoint [5] 0 0
From first dose through to 30 days after last dose of investigational products.
Secondary outcome [6] 0 0
Receptor occupancy (RO) of AK117 as monotherapy or in combination with AK104 to evaluate target engagement
Timepoint [6] 0 0
From first dose through to 30 days after last dose of investigational products.

Eligibility
Key inclusion criteria
1. Able to provide written and signed informed consent

2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.

3. Life expectancy =12 weeks

4. Females of childbearing potential and non-sterilized males who are sexually active
must use an effective method of contraception from screening until 120 days after
final dose of investigational product or women of non-childbearing potential.

5. Willing to receive blood transfusion(s) when so advised by the investigator.

6. Adequate organ function.

7. Subjects must have a histologically or cytologically confirmed advanced solid tumor
that is refractory or relapsed to the current standard therapies or which no effective
standard therapy is available.

8. At least 1 measurable lesion according to RECIST v1.1
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Concurrent enrollment in another clinical study excluding observational trials

2. Prior malignancy active within the previous 3 years except for the tumor for which a
subject is enrolled in the study

3. Active brain/central nervous system (CNS) metastases

4. Active infections requiring systemic therapy within 2 weeks prior to the first dose of
investigational product.

5. Known history of HIV.

6. Known active hepatitis B or C infections

7. Active or prior documented autoimmune disease that may relapse.

8. History of interstitial lung disease or non-infectious pneumonitis, except those
induced by radiation therapies.

9. History of defects in RBC production, or hemoglobin production or metabolism

10. Patients with clinically significant cardio-cerebrovascular disease.

11. History of severe hypersensitivity reactions to other mAbs.

12. History of organ transplantation.

13. Receiving any anticancer therapy targeting the CD47/SIRPa ; Anticancer small molecule
targeted agent within 2 weeks prior to the first dose of the investigational product;
Anticancer mAbs within 6 weeks prior to the first dose of investigational product or 5
half-lives (whichever is lesser); Other anticancer therapy within 4 weeks prior to the
first dose of the investigational product;

14. Subjects with a condition requiring systemic treatment with either corticosteroid (>10
mg daily doses)) or other immunosuppressive medications within 2 weeks prior to the
first dose of investigational product.

15. Received a live attenuated vaccine within 4 weeks prior to the first dose of
investigational product.

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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/04/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/11/2022
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital - Sydney
Recruitment hospital [2] 0 0
ICON Cancer Foundation - South Brisbane
Recruitment hospital [3] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment postcode(s) [3] 0 0
- Kurralta Park
Recruitment postcode(s) [4] 0 0
- Heidelberg

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

Ethics approval
Ethics application status

Summary
Brief summary
This was a first-in-human, Phase 1 study designed to evaluate the safety, tolerability, PK,
immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK117 as monotherapy
or in combination with AK104 in subjects with advanced or metastatic solid tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04349969
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/NCT04349969