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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04572152




Registration number
NCT04572152
Ethics application status
Date submitted
27/09/2020
Date registered
1/10/2020
Date last updated
1/10/2020

Titles & IDs
Public title
A Study of AK119 (Anti-CD73) in Combination With 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 Anti-tumor Activity of AK119 in Combination With AK104 in Subjects With Advanced or Metastatic Solid Tumors.
Secondary ID [1] 0 0
AK119-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AK119
Other interventions - AK104

Experimental: AK119/ AK104 - Single-arm


Other interventions: AK119
Subjects will receive AK119 by intravenous administration.

Other interventions: AK104
After AK119 IV, on the same day 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 study drug
Primary outcome [2] 0 0
Number of participants with a Dose Limiting Toxicity (DLT) - DLTs will be assessed during the first 6 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 6 weeks of treatment.
Timepoint [2] 0 0
During the first 6 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 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) based on RECIST Version 1.1.
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Maximum observed concentration (Cmax) of AK119 and AK104 - The endpoints for assessment of PK include serum concentrations of AK119 and AK104 at different timepoints after study drug administration.
Timepoint [3] 0 0
From first dose of study drug through 30 days after last dose of study drug
Secondary outcome [4] 0 0
Minimum observed concentration (Cmin) of AK119 and AK104 at steady state - The endpoints for assessment of PK include serum concentrations of AK119 and AK104 at different timepoints after study drug administration.
Timepoint [4] 0 0
From first dose of study drug through 30 days after last dose of study drug
Secondary outcome [5] 0 0
Number of subjects who develop detectable anti-drug antibodies (ADAs) - The immunogenicity of AK119 and AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).
Timepoint [5] 0 0
From first dose of study drug through 90 days after last dose of study drug

Eligibility
Key inclusion criteria
1. Has provided written informed consent

2. Age = 18 years.

3. In dose-escalation cohorts (Phase 1a), subjects must have histologically or
cytologically confirmed advanced or metastatic solid tumor that is refractory or
relapsed to the current standard therapies, or for which no effective standard therapy
is available, or whereby standard therapy has been refused.

4. In pharmacodynamic-confirmation cohorts (Phase 1a), additional enrolled subjects must
have histologically or cytologically confirmed selected advanced or metastatic solid
tumors, refractory or relapsed to the current standard therapies, or for which no
effective standard therapy is available. Other tumor types can be considered after
discussion with the Sponsor.

5. In dose-expansion cohorts (Phase 1b), subjects with specific tumor types will be
enrolled. Subjects must have received no more than three prior lines of systemic
therapy (including approved and investigational treatments) for advanced or metastatic
disease. Other cohorts of different tumor types may be added based on the emerging
pharmacodynamic and anti-tumor response data.

6. Subjects must have measurable lesions according to RECIST v1.1. A previously
irradiated lesion can be considered a target lesion if the lesion is measurable per
RECIST v1.1, and there is objective evidence of interval increase in size since
radiotherapy.

7. For dose-escalation cohorts (Phase 1a), subjects must have available archived tumor
tissue sample (block or a minimum of 10 unstained slides of formalin-fixed
paraffin-embedded [FFPE] tissues) to allow for correlative biomarker studies.

8. For pharmacodynamic-confirmation cohorts (Phase 1a) and dose-expansion cohorts (Phase
1b), subjects must be willing to provide 2 fresh biopsy samples (pre-treatment and on
treatment), where clinically appropriate.

9. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to1.

10. Adequate organ function

11. Life expectancy =12 weeks;

12. Females of childbearing potential must be willing to use a highly effective method of
birth control for the duration of the study, and within 120 days after the last dose
of investigational product.

13. Non-sterile males must be willing to use a highly effective method of birth control
for the duration of the study and within 120 days after the last dose of
investigational product.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Receipt of the following treatments or procedures:

1. Anticancer small-molecule targeted agent (e.g., tyrosine kinase inhibitor) within
2 weeks prior to the first dose of investigational product;

2. Anti-PD-1/PD-L1 mAb within 4 weeks prior to the first dose of investigational
product;

3. Prior use of approved or investigational anti-CTLA-4 therapy, anti-CD73 therapy
or adenosine 2A receptor inhibitors, or any other antibody or drug targeting T
cell costimulation or immune checkpoint pathways such as ICOS, or agonists such
as CD40, CD137, GITR, OX40 etc.

4. Other anticancer mAb within 4 weeks or 5 half-lives (whichever is less) prior to
the first dose of investigational product;

5. Other anticancer therapy (e.g., chemotherapy, radiotherapy, etc.) within 4 weeks
prior to the first dose of investigational product; [Note: Palliative
radiotherapy > 1 week prior to first dose is allowed]

6. Any major surgery (e.g., laparotomy, thoracotomy, removal of organ[s]) within 4
weeks prior to the first dose of investigational product;

7. Any other non-approved investigational product or procedure within 4 weeks prior
to the first dose of investigational product, or concurrent participation in
another therapeutic clinical study;

2. Any condition that required systemic treatment with corticosteroids (> 10 mg daily
prednisone or equivalent) or other immunosuppressive agents within 14 days prior to
the first dose of investigational product.

3. Receipt of live attenuated vaccines within 4 weeks prior to the first dose of
investigational product; Note: seasonal vaccine for influenza which is generally
inactivated is allowed.

4. Prior organ transplantation;

5. 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 cancer or carcinoma in situ of the cervix or
breast;

6. Subjects with history of brain metastases that have been treated may participate
provided they show evidence of stable supra-tentorial lesions at Screening (based on 2
sets of brain images, performed = 4 weeks apart, and obtained after the brain
metastases treatment).

7. Active infections (including tuberculosis) requiring systemic antibacterial,
antifungal, or antiviral therapy within 14 days prior to the first dose of
investigational products. Note: antiviral therapy is permitted for patients with viral
hepatitis;

8. Known history of human immunodeficiency virus (HIV) infection;

9. Known active hepatitis B or C infections (Active hepatitis B is defined as a known
positive Hepatitis B surface antigen [HBsAg] result. Active hepatitis C is defined by
a known positive Hepatitis C virus [HCV] antibody with detectable HCV ribonucleic acid
[RNA] results);

10. Active autoimmune diseases or history of autoimmune diseases that may relapse. Note:
Subjects with controlled type 1 diabetes mellitus, thyroiditis in euthyroid state or
hypothyroidism well managed by hormone replacement therapy (HRT), or skin diseases not
requiring systemic treatment (e.g., vitiligo, psoriasis) are eligible;

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

12. Uncontrolled massive ascites or pleural effusion, as determined by the Investigator;

13. Patients with clinically significant cardio-cerebrovascular disease.

14. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) = 470 msec
calculated from 3 ECGs (within 5 minutes at least 1 minute apart);

15. Uncontrolled intercurrent illness including, but not limited to, uncontrolled
hypertension, uncontrolled diabetes, uncontrolled endocrinopathy, severe active peptic
ulcer disease or gastritis, or psychiatric illness/social situations that would limit
compliance with study requirement or compromise the ability of the subject to give
written informed consent;

16. History of severe hypersensitivity reactions to other mAbs;

17. Toxicities of prior anticancer therapy have not resolved to NCI-CTCAE version 5.0
Grade =1, or to levels dictated in the inclusion/exclusion criteria, except toxicities
not considered a safety risk (e.g., alopecia, neuropathy, or asymptomatic laboratory
abnormalities);

18. Pregnant or breastfeeding women;

19. Any other conditions that, in the opinion of the Investigator, would interfere with
evaluation of the investigational product or interpretation of subject safety or study
results.

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
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
Recruitment hospital [1] 0 0
Blacktown Cancer and Haematology Centre (Blacktown Hospital) - Blacktown
Recruitment hospital [2] 0 0
ICON Cancer Centre - South Brisbane
Recruitment hospital [3] 0 0
Ashford Cancer Centre - Adelaide
Recruitment hospital [4] 0 0
Monash Health - Clayton
Recruitment hospital [5] 0 0
Alfred Health (The Alfred Hospital) - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5037 - Adelaide
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Akeso
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a first-in-human (FIH), Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and
Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of
AK119 (Anti-CD73) in Combination with AK104 in Subjects with Advanced or Metastatic Solid
Tumors.
Trial website
https://clinicaltrials.gov/show/NCT04572152
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
Address 0 0
Country 0 0
Phone 0 0
+86 (0760) 8987 3999
Fax 0 0
Email 0 0
global.trials@akesobio.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04572152