A Multicenter, Open-label, Phase II Study of AK104（an Anti-PD-1 and Anti-CTLA-4 Bispecific Antibody) in the Treatment of Recurrent or Metastatic Cervical Cancer
Overview
- Phase
- Phase 2
- Intervention
- AK104
- Conditions
- Recurrent or Metastatic Cervical Cancer
- Sponsor
- Akeso
- Enrollment
- 50
- Locations
- 2
- Primary Endpoint
- AE
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a multicenter, open-label, phase II clinical study conducted in China. All subjects will receive AK104 in combination with standard treatment regimens or AK104 alone. The primary end point is safety. The secondary end point is efficacy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written and signed informed consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or
- •Estimated life expectancy of ≥3 months.
- •Histologically or cytologically confirmed recurrent or metastatic cervical cancer that not appropriate for radical surgical resection and/or radical radiotherapy or chemotherapy.
- •For cohort A and B: The pathological types were squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma. No previous systematic treatment for recurrent or metastatic cervical cancer.
- •For cohort C: The pathological types were squamous cell carcinoma or adenosquamous cell carcinoma. Subjects must have received platinum-containing dual-drug chemotherapy combination with bevacizumab during or after the recurrence or metastasis phase and have demonstrated radiologically confirmed disease progression during or after treatment. Subjects will have no more than 2 lines of systemic therapy in the recurrence or metastatic stages.
- •Subjects must have at least one measurable lesion in accordance with RECIST v1.
- •All subjects must provide archived or freshly acquired tumor tissue samples, approximately 5 unstained FFPE pathological slides.
- •Adequate organ function.
- •Females of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first administration. If having sex with an unsterilized male partner, the subject must use an acceptable contraceptive method since screening and must agree to continue using this contraceptive method for 120 days after the last administration.
Exclusion Criteria
- •Subjects had clinically significant hydronephrosis that could not be relieved by nephrostomy or urethral stenting, as determined by the investigator.
- •Other active malignancies within 2 years prior to the first administration. Subjects with locally curable tumors that appear to be cured, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the breast, were not excluded.
- •Have received other study drugs or study devices within 4 weeks prior to the first administration.
- •Is participating in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period for an interventional study.
- •Subjects received systemic treatment with either proprietary Chinese drugs with anti-tumor indications or herbal medicines with anti-tumor effects, or immunomodulatory drugs (thymopeptide, interferon, interleukin) within 2 weeks prior to the first administration.
- •Had received the last course of systemic antitumor therapy within 4 weeks prior to the first administration; Underwent major surgery within 3 weeks; Received non-specific immunoregulatory system treatment within 2 weeks; Any herbal or proprietary Chinese medicine with anti-tumor indications was received within 2 weeks.
- •Have previously received immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as antibodies targeting ICOS, CD40, CD137, GITR, and Ox40 targets, etc.), immune cell therapy, etc. Any treatment targeted at the immune mechanism of tumor.
- •Subjects had an active autoimmune disease that required systemic treatment within 2 years prior to the first administration, or an autoimmune disease that was determined by the investigator to be likely to recur or for which treatment was planned.
- •Active or documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, or chronic diarrhea).Inability to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting, diarrhea or other gastrointestinal disorders that can seriously affect the administration and absorption of drug.
- •Subjects requiring systemic treatment with glucocorticoids (\> 10 mg/ day equivalent dose of prednisone) or other immunosuppressive agents within 14 days prior to the first administration.
Arms & Interventions
AK104
AK104 IV every 2 weeks (Q2W)
Intervention: AK104
AK104+Paclitaxel+Cisplatin/Carboplatin
AK104 intravenously(IV) every 3 weeks (Q3W) Paclitaxel 175mg/m2 IV every 3 weeks (Q3W) Cisplatin 50mg/m2 or Carboplatin AUC5 IV every 3 weeks (Q3W)
Intervention: AK104
AK104+Paclitaxel+Cisplatin/Carboplatin
AK104 intravenously(IV) every 3 weeks (Q3W) Paclitaxel 175mg/m2 IV every 3 weeks (Q3W) Cisplatin 50mg/m2 or Carboplatin AUC5 IV every 3 weeks (Q3W)
Intervention: Paclitaxel
AK104+Paclitaxel+Cisplatin/Carboplatin
AK104 intravenously(IV) every 3 weeks (Q3W) Paclitaxel 175mg/m2 IV every 3 weeks (Q3W) Cisplatin 50mg/m2 or Carboplatin AUC5 IV every 3 weeks (Q3W)
Intervention: Cisplatin or Carboplatin
AK104+Bevacizumab+Paclitaxel+Cisplatin/Carboplatin
AK104 every 3 weeks (Q3W) Bevacizumab 15mg/kg IV every 3 weeks (Q3W) Paclitaxel 175mg/m2 IV every 3 weeks (Q3W) Cisplatin 50mg/m2 or Carboplatin AUC5 IV every 3 weeks (Q3W)
Intervention: AK104
AK104+Bevacizumab+Paclitaxel+Cisplatin/Carboplatin
AK104 every 3 weeks (Q3W) Bevacizumab 15mg/kg IV every 3 weeks (Q3W) Paclitaxel 175mg/m2 IV every 3 weeks (Q3W) Cisplatin 50mg/m2 or Carboplatin AUC5 IV every 3 weeks (Q3W)
Intervention: Bevacizumab
AK104+Bevacizumab+Paclitaxel+Cisplatin/Carboplatin
AK104 every 3 weeks (Q3W) Bevacizumab 15mg/kg IV every 3 weeks (Q3W) Paclitaxel 175mg/m2 IV every 3 weeks (Q3W) Cisplatin 50mg/m2 or Carboplatin AUC5 IV every 3 weeks (Q3W)
Intervention: Paclitaxel
AK104+Bevacizumab+Paclitaxel+Cisplatin/Carboplatin
AK104 every 3 weeks (Q3W) Bevacizumab 15mg/kg IV every 3 weeks (Q3W) Paclitaxel 175mg/m2 IV every 3 weeks (Q3W) Cisplatin 50mg/m2 or Carboplatin AUC5 IV every 3 weeks (Q3W)
Intervention: Cisplatin or Carboplatin
Outcomes
Primary Outcomes
AE
Time Frame: From the time of informed consent signed through 90 days after the last dose of AK104
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment
Secondary Outcomes
- Minimum observed concentration (Cmin) of AK104 at steady state(From first dose of AK104 through 30 days after last dose of AK104)
- Disease control rate (DCR)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of AK104 through 30 days after last dose of AK104)
- Expression of PD-L1 in tumor tissue samples(Baseline (Tumor tissue samples must be provided to the research center or central laboratory prior to initial administration))
- Objective response rate (ORR)(Up to 2 years)
- Duration of response (DoR)(Up to 2 years)
- Progression-free survival (PFS)(Up to 2 years)