Clinical Trials /

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

NCT04380805

Description:

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.

Related Conditions:
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: AK104-201-AU
  • NCT ID: NCT04380805

Conditions

  • Recurrent Cervical Cancer
  • Metastatic Cervical Cancer

Interventions

DrugSynonymsArms
AK104AK104

Purpose

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 Arms

NameTypeDescriptionInterventions
AK104ExperimentalAK104 monotherapy
  • AK104

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:ORR assessed by Investigator
Time Frame:Up to 2 years
Safety Issue:
Description:The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR per RECIST v1.1.
Measure:Disease control rate (DCR)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Duration of Response (DoR)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Progression-free survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Number of participants with adverse events (AEs)
Time Frame:From the time of informed consent signed through 30 days after the last dose, up to 2 years
Safety Issue:
Description:
Measure:Minimum observed concentration (Cmin) of AK104 at steady state
Time Frame:From first dosing date of AK104 through 30 days post last dose of AK104, up to 2 years
Safety Issue:
Description:
Measure:Number of subjects who develop detectable anti-drug antibodies
Time Frame:From first dosing date of AK104 through 90 days post last dose of AK104, up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Akeso

Last Updated

May 7, 2020