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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04349969




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

Titles & IDs
Public title
Phase 1, Dose Escalation and Dose Expansion Study of AK117, a CD47-targeting Antibody
Scientific title
A Phase 1, Multicenter, Open Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 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

Experimental: Treatment - AK117 monotherapy


Treatment: Drugs: AK117
An intravenous (IV) infusion of AK117 as monotherapy. 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

Intervention code [1] 0 0
Treatment: Drugs
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 30 days after the last dose of AK117
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) - ORR defined as the proportion of subjects who achieves a best overall response of CR or PR, assessed by Investigator per RECIST Version 1.1 for solid tumor or the Lugano 2014 Classification for lymphoma
Timepoint [1] 0 0
Up to 2 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).
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Maximum observed concentration (Cmax) of AK117 - The endpoints for assessment of PK of AK104 include serum concentrations of AK117 at different timepoints after AK117 administration.
Timepoint [3] 0 0
From first dose of AK117 through to 30 days after last dose of AK117
Secondary outcome [4] 0 0
Minimum observed concentration (Cmin) of AK117 at steady state - The endpoints for assessment of PK of AK104 include serum concentrations of AK117 at different timepoints after AK117 administration.
Timepoint [4] 0 0
From first dose of AK117 through to 30 days after last dose of AK117
Secondary outcome [5] 0 0
Number of subjects who develop detectable anti-drug antibodies (ADAs) - The immunogenicity of AK117 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Timepoint [5] 0 0
From first dose of AK117 through to 30 days after last dose of AK117

Eligibility
Key inclusion criteria
All Subjects

1. Able to provide written and signed informed consent and any locally required
authorization obtained from the subject/legal representative, which must be obtained
prior to performing any protocol related procedures, including screening evaluations.

2. Men or women aged =18 years at the time of study entry.

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

4. Life expectancy =12 weeks.

5. Female subjects are eligible to participate if at least 1 of following conditions
applies:For a woman of childbearing potential (WOCBP) who is sexually active with a
non sterilized male partner: must have a negative pregnancy test at the Screening
Visit (within 3 days prior to the first dose of the investigational product), should
not be lactating, and must agree to use 2 methods of contraception up to 120 days
after the last dose of investigational product; Is a woman of non childbearing
potential.

6. Non sterilized male subjects who are sexually active with female partners of
childbearing potential must agree to use contraception up to 120 days after the last
dose of investigational product.

7. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures as specified in the protocol.

8. Willing to receive blood transfusion(s) when so advised by the investigator. Subjects
with Solid Tumors (Parts A, B, and C)

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

10. Subject must have at least 1 measurable lesion according to RECIST v1.1. A previously
irradiated lesion can be considered a target lesion if the lesion is well defined,
measurable per RECIST v1.1, and there is objective evidence of interval increase in
size since radiotherapy.

11. Adequate organ function. Subjects with Lymphomas (Part B cohort expansion and Part C)

12. Subjects must have histologically confirmed non-Hodgkin lymphoma (NHL), which may
include transformed lymphoma, relapsed or refractory to autologous hematopoietic stem
cell transplantation, or at least 2 lines of prior chemotherapy.

13. Subjects must have disease that is measurable or assessable for response as per Lugano
Classification 2014.

14. Adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
All Subjects

1. Concurrent enrollment in another clinical study, unless it is an observational (non
interventional) clinical study or the follow up period of an interventional study.

2. Prior malignancy active within the previous 3 years except for the tumor for which a
subject is enrolled in the study, and locally curable cancers that have been
apparently cured, such as basal cell skin cancer, or carcinoma in situ of the cervix
or breast.

3. Active brain/central nervous system (CNS) metastases (defined as neurologically stable
for <4 weeks and/or symptomatic and/or requiring treatment with steroids and/or
leptomeningeal disease).

4. Active infections (including tuberculosis) requiring systemic antibacterial,
antifungal, or antiviral therapy within 14 days prior to the first dose of
investigational product.

5. Known history of testing positive for human immunodeficiency virus (HIV) or known
active acquired immunodeficiency syndrome.

6. Known active hepatitis B or C infections (known positive hepatitis B surface antigen
[HBsAg] result or positive hepatitis C virus [HCV] antibody with detectable HCV
ribonucleic acid [RNA] results).

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

8. History of interstitial lung disease or noninfectious pneumonitis, except for those
induced by radiation therapies.

9. History of hemolytic anemia of any cause (including Evans syndrome) within 3 months
prior to the first dose of investigational product.

10. History of defects in RBC production, or hemoglobin production or metabolism (eg,
glucose 6 phosphate dehydrogenase deficiency, thalassemia, sickle cell disease,
hereditary spherocytosis).

11. Patients with clinically significant cardio cerebrovascular disease.

12. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
NCI CTCAE v5.0 Grade 0 or 1, or to levels dictated in the eligibility criteria with
the exception of toxicities not considered a safety risk.

13. History of hemophagocytic lymphohistiocytosis.

14. History of severe hypersensitivity reactions to other mAbs.

15. History of organ transplantation.

16. Known allergy or reaction to any component of the investigational product formulation.

17. Receipt of the following treatments or procedures: Any anticancer therapy targeting
the CD47/SIRPa signaling axis; Anticancer small molecule targeted agent within 2 weeks
prior to the first dose of 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 (eg, chemotherapy, radiotherapy, etc) within 4 weeks
prior to the first dose of investigational product.

18. Subjects with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily doses of prednisone or equivalent) or other immunosuppressive
medications within 14 days prior to the first dose of investigational product.

19. Receipt of live attenuated vaccines 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
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital - Sydney
Recruitment hospital [2] 0 0
ICON Cancer Foundation - South Brisbane
Recruitment hospital [3] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
Linear Clinical Research/Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Akeso
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Akesobio Australia Pty Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a first-in-human, Phase 1, multicenter, open label, single arm, integrated 3-part
dose escalation and dose expansion study designed to evaluate the safety, tolerability, PK,
immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK117 administered
intravenously to adult subjects with relapsed/refractory advanced or metastatic solid tumors
or lymphomas.
Trial website
https://clinicaltrials.gov/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
Kon Yew Kwek, MD
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/NCT04349969