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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04380805




Registration number
NCT04380805
Ethics application status
Date submitted
1/05/2020
Date registered
8/05/2020
Date last updated
21/09/2020

Titles & IDs
Public title
A Study of AK104, a PD-1/CTLA-4 Bispecific Antibody in Subjects With Recurrent/Metastatic Cervical Cancer
Scientific title
A Phase 2, Multicenter, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of AK104 in Subjects With Recurrent or Metastatic Cervical Cancer
Secondary ID [1] 0 0
AK104-201-AU
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Cervical Cancer 0 0
Metastatic Cervical Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)

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

Experimental: AK104 - AK104 monotherapy


Other interventions: AK104
All subjects will receive AK104 as a single agent at a dose of 6 mg/kg Q2W (Day 1 and Day 15 of each 28 day treatment cycle) via IV infusion.

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

Outcomes
Primary outcome [1] 0 0
Objective response rate (ORR) assessed by Independent Radiological Review Committee (IRRC)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [1] 0 0
ORR assessed by Investigator - The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR per RECIST v1.1.
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
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 2 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 2 years
Secondary outcome [5] 0 0
Number of participants with adverse events (AEs)
Timepoint [5] 0 0
From the time of informed consent signed through 30 days after the last dose, up to 2 years
Secondary outcome [6] 0 0
Minimum observed concentration (Cmin) of AK104 at steady state
Timepoint [6] 0 0
From first dosing date of AK104 through 30 days post last dose of AK104, up to 2 years
Secondary outcome [7] 0 0
Number of subjects who develop detectable anti-drug antibodies
Timepoint [7] 0 0
From first dosing date of AK104 through 90 days post last dose of AK104, up to 2 years

Eligibility
Key inclusion criteria
1. Able to provide written and signed informed consent and any locally required
authorization obtained from the subject/legal representative.

2. Women aged =18 years at the time of study entry.

3. Subjects must have histologically or cytologically confirmed recurrent or metastatic
squamous carcinoma or adenosquamous carcinoma of the cervix, and meet the following
criteria: disease progression confirmed by radiologic imaging during or following
prior platinum based doublet chemotherapy, with or without bevacizumab for recurrent
or metastatic cervical cancer; No more than 2 prior systemic therapies in the
recurrent or metastatic setting.

4. Subjects must have measurable lesions according to RECIST v1.1. The presence of
measurable lesions must be confirmed by the IRRC. A previously irradiated lesion is
not considered measurable and cannot be selected as a target lesion.

5. Available archived tumor tissue sample - block or a minimum of 10 unstained slides of
formalin fixed paraffin embedded [FFPE] tissues - preferably from the most recent
biopsy of a tumor lesion collected either at the time of or after the diagnosis of
locally advanced, recurrent, and/or metastatic disease has been made.

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

7. Life expectancy =12 weeks.

8. Adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Concurrent enrollment in another clinical study, unless it is an observational
(noninterventional) clinical study or the follow-up period of an interventional study.

2. Histological types of cervical cancer other than squamous carcinoma and adeno-squamous
carcinoma (eg, adenocarcinoma, small cell carcinoma, clear cell carcinoma, sarcoma,
etc).

3. Prior malignancy active within the previous 2 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 breast.

4. Brain/central nervous system (CNS) metastases.

5. Clinically significant hydronephrosis, as determined by the investigator, not
alleviated by nephrostomy or ureteral stent

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

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

8. 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).

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

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

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 severe hypersensitivity reactions to other mAbs.

14. Prior allogeneic stem cell transplantation or organ transplantation.

15. Known allergy or reaction to any component of the AK104 formulation.

16. Receipt of the following treatments or procedures: anticancer small molecule targeted
agent within 2 weeks, radiation therapy within 2 weeks, other anticancer therapy
within 4 weeks, any major surgery within 4 weeks, any other investigational product or
procedure within 4 weeks, or agents with immunomodulatory effect within 2 weeks prior
to the first dose of investigational product.

17. 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.

18. Receipt of live attenuated vaccines within 30 days prior to the first dose of
investigational product.

19. Prior exposure to any experimental antitumor vaccines, or any agent targeting T-cell
costimulation or immune checkpoint pathways (eg, anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CTLA-4, anti-CD137 or anti-OX40 antibody, etc).

20. 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.

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 2
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
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [3] 0 0
Adelaide Cancer Centre - Adelaide
Recruitment hospital [4] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [5] 0 0
ICON Cancer Centre - Brisbane
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Nedlands
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
- Blacktown
Recruitment postcode(s) [5] 0 0
- Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Oklahoma
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
New Zealand
State/province [12] 0 0
Auckland

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 Phase 2, global, multicenter, open label, single arm study designed to evaluate the
efficacy, safety, tolerability, pharmacokinetic (PK), and immunogenicity of AK104 monotherapy
in adult subjects with previously treated recurrent or metastatic cervical carcinoma.
Trial website
https://clinicaltrials.gov/show/NCT04380805
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Leslie Randall, MD
Address 0 0
Virginia Commonwealth University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kon Yew Kwek, BMBCh, DPhil
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/NCT04380805