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A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK127 in Combination With AK104 in Advanced and Metastatic Solid Tumours

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05021120
Recruitment Status : Recruiting
First Posted : August 25, 2021
Last Update Posted : January 9, 2023
Sponsor:
Information provided by (Responsible Party):
Akeso ( Akesobio Australia Pty Ltd )

Tracking Information
First Submitted Date  ICMJE August 12, 2021
First Posted Date  ICMJE August 25, 2021
Last Update Posted Date January 9, 2023
Actual Study Start Date  ICMJE October 12, 2021
Estimated Primary Completion Date January 10, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2021)
  • Incidence and Nature of Adverse Events (AEs) [ Time Frame: From the time of informed consent signed through to 90 days after end of treatment ]
    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.
  • Number of participants with a Dose Limiting Toxicity (DLT) [ Time Frame: Within the first six weeks of treatment ]
    DLTs will be assessed during the first treatment cycle and assessed as having a suspected relationship to study drug according to pre-specific criteria in the protocol.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2021)
  • Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
  • Disease control rate (DCR) [ Time Frame: Up to 2 years ]
    Progression-free survival is defined as the time from the start of treatment with AK127 + AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.
  • Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    Progression-free survival is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first.
  • Overall survival (OS) [ Time Frame: Up to 2 years ]
    Overall survival is defined as the time from the start of treatment until death due to any cause.
  • Area under the curve (AUC) of AK127+AK104 for assessment of pharmacokinetics [ Time Frame: From first dose of treatment through to 90 days after end of treatment ]
    The endpoints for assessment of PK including serum concentrations of AK127+AK104 at different timepoints after treatment administration.
  • Maximum observed concentration (Cmax) of AK127 + AK104 [ Time Frame: From first dose of treatment through to 90 days after end of treatment. ]
    The endpoints for assessment of PK of AK127+AK104 include serum concentrations of AK127+AK104 at different timepoints after treatment administration.
  • Minimum observed concentration (Cmin) of AK127+AK104 [ Time Frame: From first dose of treatment through to 90 days after end of treatment ]
    The endpoints for assessment of PK of AK127+AK104 include serum concentrations of AK127+AK104 at different timepoints after treatment administration.
  • Number of subjects who develop detectable anti-drug antibodies (ADAs) [ Time Frame: From first dose of treatment through to 90 days after end of treatment ]
    The immunogenicity of AK127+AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK127 in Combination With AK104 in Advanced and Metastatic Solid Tumours
Official Title  ICMJE A Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumour Activity of AK127 in Combination With AK104 in Subjects With Advanced or Metastatic Solid Tumours
Brief Summary A Phase 1 study to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK127 in combination with AK104.
Detailed Description This is a , Phase 1, first-in-human, multicenter, open label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK127 in combination with AK104 in subjects with advanced and metastatic solid tumours. The study comprises of 2 phases: a dose escalation phase and a dose expansion phase. Dose escalation for AK127 will occur using the 3+3+3 model given with a fixed regimen of AK104. Dose expansion will open at the discretion of the Sponsor.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Sequential Assignment
Masking: None (Open Label)
Masking Description:
None (open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced or Metastatic Solid Tumours
Intervention  ICMJE
  • Drug: AK127
    Subjects will receive AK127 by intravenous administration
  • Drug: AK104
    After AK127 infusion, on the same day subjects will receive AK104 by intravenous administration
Study Arms  ICMJE Experimental: Intervention/treatment
Experimental
Interventions:
  • Drug: AK127
  • Drug: AK104
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 24, 2021)		 143
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 7, 2025
Estimated Primary Completion Date January 10, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Written and signed informed consent
  2. In Phase 1a, patients with relapsed or refractory advanced solid malignancies
  3. In Phase 1b, patients must have received no more than three prior lines of systemic therapy
  4. Subject must have at least one measurable lesion according to RECIST Version1.1.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
  6. Available archived or fresh tumor tissue
  7. Adequate organ function.
  8. For dose-expansion cohorts (Phase 1b), subjects must be willing to provide two fresh biopsy samples (pre-treatment and on treatment), where clinically appropriate.
  9. Females of childbearing potential and non-sterilized males who are sexually active must use an effective method of contraception from screening until 120 days after final dose of investigational product.

Exclusion Criteria:

  1. History of severe hypersensitivity reactions to other mAbs.
  2. Subjects with a condition requiring systemic treatment with either corticosteroid (> 10 mg daily ) or other immunosuppressive medications within 2 weeks of study drug administration.
  3. Prior use of approved or investigational anti-TIGIT, anti-PVRIG, or anti-CD96 therapy
  4. Receiving any Other anticancer therapy (e.g., chemotherapy, radiotherapy, biologic or hormonal therapy for cancer treatment. etc.) within 4 weeks prior to the first dose of treatment
  5. Any major surgery within 4 weeks prior to the first dose of treatment
  6. Receiving agents with immunomodulatory effect within 2 weeks prior to the first dose of treatment.
  7. Active or prior documented inflammatory bowel disease
  8. History of organ transplant.
  9. History of interstitial lung disease, noninfectious pneumonitis except for those induced by radiation therapies.
  10. Known active hepatitis B or C infections or history of HIV.
  11. Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product.
  12. Patients with severe heart and lung dysfunction.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Baiyong Li +86 (0760) 8987 3999 global.trials@akesobio.com
Contact: Dennis Xia global.trials@akesobio.com
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05021120
Other Study ID Numbers  ICMJE AK127-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Akeso ( Akesobio Australia Pty Ltd )
Original Responsible Party Akeso
Current Study Sponsor  ICMJE Akesobio Australia Pty Ltd
Original Study Sponsor  ICMJE Akeso
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Akeso
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP