A Study of AK104, a PD-1/CTLA-4 Bispecific Antibody in Subjects With Recurrent/Metastatic Cervical Cancer

Recurrent Cervical Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04380805
• Other study ID #: AK104-201-AU
• Status: Completed
• Phase: Phase 2
• Start date: July 15, 2020
• Est. completion date: September 15, 2022

Study information

• Verified date: October 2022
• Source: Akeso
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 15, 2022
• Est. primary completion date: August 29, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Metastatic Cervical Cancer
• Recurrence
• Recurrent Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
Australia	Ashford Cancer Centre Research	Adelaide
Australia	Blacktown Hospital	Blacktown
Australia	ICON Cancer Centre	Brisbane
Australia	Monash Health	Clayton	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
New Zealand	Auckland City Hospital	Grafton	Auckland
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Augusta University Medical Center	Augusta	Georgia
United States	Chattanooga's Program In Women's Oncology	Chattanooga	Tennessee
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Texas Oncology-Fort Worth Cancer Center	Fort Worth	Texas
United States	Lyndon B. Johnson Hospital (MD Anderson)	Houston	Texas
United States	Monter Cancer Center	Lake Success	New York
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Tennessee Oncology - Centennial Clinic	Nashville	Tennessee
United States	The Blavatnik Family - Chelsea Medical Center at Mount Sinai	New York	New York
United States	Womens Cancer Research Foundation	Newport Beach	California
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	BRCR Medical Center	Plantation	Florida
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Pacific Gynecology Specialists, P. C.	Seattle	Washington
United States	Maryland Oncology Hematology (Plum Orchard)	Silver Spring	Maryland
United States	Texas Oncology (Woodlands)	The Woodlands	Texas
United States	Oklahoma Cancer Specialists and Research Institute, LLC	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Akeso	Akesobio Australia Pty Ltd

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

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