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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Cervical Cancer; Recurrent Cervical Cancer
• Intervention / Treatment: Biological: AK104

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Ashford Cancer Centre Research
  • Blacktown, Australia
    • Blacktown Hospital
  • Brisbane, Australia
    • Icon Cancer Centre
  • Victoria
    • Clayton, Victoria, Australia
      • Monash Health
  • Western Australia
    • Nedlands, Western Australia, Australia
      • Sir Charles Gairdner Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand
      • Auckland City Hospital
• United States
  • California
    • Newport Beach, California, United States, 92663
      • Womens Cancer Research Foundation
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
    • Plantation, Florida, United States, 33322
      • BRCR Medical Center
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60005-2380
      • Illinois Cancer Specialists
  • Maryland
    • Silver Spring, Maryland, United States, 20904
      • Maryland Oncology Hematology (Plum Orchard)
  • New York
    • Lake Success, New York, United States, 11042
      • Monter Cancer Center
    • New York, New York, United States, 10011
      • The Blavatnik Family - Chelsea Medical Center at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute, LLC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Chattanooga's Program in Women's Oncology
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Centennial Clinic
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology-Fort Worth Cancer Center
    • Houston, Texas, United States, 77026
      • Lyndon B. Johnson Hospital (MD Anderson)
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology (Woodlands)
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists, P. C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104; AK104 monotherapy	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR) assessed by Independent Radiological Review Committee (IRRC)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Akeso
• Collaborators: Akesobio Australia Pty Ltd
• Investigators: Study Chair: Leslie Randall, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2020
• Primary Completion (Actual): August 29, 2022
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: May 1, 2020
• First Submitted That Met QC Criteria: May 7, 2020
• First Posted (Actual): May 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Disease Attributes; Uterine Cervical Neoplasms; Recurrence
• Other Study ID Numbers: AK104-201-AU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No