Clinical trial NCT04380805: A Study of AK104, a PD-1/CTLA-4 Bispecific Antibody in Subjects With Recurrent/Metastatic Cervical Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Cervical Cancer
Metastatic Cervical Cancer
Lead sponsor: Akeso
Sponsor class: INDUSTRY
Collaborators: name: Akesobio Australia Pty Ltd
First posted: 2020-05-08
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR) assessed by Independent Radiological Review Committee (IRRC)
timeFrame: Up to 2 years
Secondary outcomes:
measure: ORR assessed by Investigator
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Duration of Response (DoR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Number of participants with adverse events (AEs)
timeFrame: From the time of informed consent signed through 30 days after the last dose, up to 2 years
measure: Minimum observed concentration (Cmin) of AK104 at steady state
timeFrame: From first dosing date of AK104 through 30 days post last dose of AK104, up to 2 years
measure: Number of subjects who develop detectable anti-drug antibodies
timeFrame: From first dosing date of AK104 through 90 days post last dose of AK104, up to 2 years
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Womens Cancer Research Foundation
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center
state: Florida
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology (Plum Orchard)
state: Maryland
city: Lake Success
country: United States
facility: Monter Cancer Center
state: New York
city: New York
country: United States
facility: The Blavatnik Family - Chelsea Medical Center at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute, LLC
state: Oklahoma
city: Chattanooga
country: United States
facility: Chattanooga's Program In Women's Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology - Centennial Clinic
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth Cancer Center
state: Texas
city: Houston
country: United States
facility: Lyndon B. Johnson Hospital (MD Anderson)
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology (Woodlands)
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Pacific Gynecology Specialists, P. C.
state: Washington
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Adelaide
country: Australia
facility: Ashford Cancer Centre Research
city: Blacktown
country: Australia
facility: Blacktown Hospital
city: Brisbane
country: Australia
facility: ICON Cancer Centre
city: Grafton
country: New Zealand
facility: Auckland City Hospital
state: Auckland
Study officials:
affiliation: Virginia Commonwealth University
name: Leslie Randall, MD
role: STUDY_CHAIR
References: