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A Study of AK119 (Anti-CD73) in Combination With AK104 in Subjects With Advanced Solid Tumors

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: NCT04572152
Recruitment Status : Not yet recruiting
First Posted : October 1, 2020
Last Update Posted : October 1, 2020
Sponsor:
Information provided by (Responsible Party):
Akeso

Brief Summary:
This is a first-in-human (FIH), Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 (Anti-CD73) in Combination with AK104 in Subjects with Advanced or Metastatic Solid Tumors.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Solid Tumors Biological: AK119 Biological: AK104 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 195 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description: Open label
Primary Purpose: Treatment
Official Title: A Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 in Combination With AK104 in Subjects With Advanced or Metastatic Solid Tumors.
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : January 2022

Arm Intervention/treatment
Experimental: AK119/ AK104
Single-arm
Biological: AK119
Subjects will receive AK119 by intravenous administration.

Biological: AK104
After AK119 IV, on the same day subjects will receive AK104 by intravenous administration.




Primary Outcome Measures :
  1. Number of participants with adverse events (AEs) [ Time Frame: From the time of informed consent signed through 90 days after the last dose of study drug ]
    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.

  2. Number of participants with a Dose Limiting Toxicity (DLT) [ Time Frame: During the first 6 weeks ]
    DLTs will be assessed during the first 6 weeks of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 6 weeks of treatment.


Secondary Outcome Measures :
  1. 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

  2. Disease control rate (DCR) [ Time Frame: Up to 2 years ]
    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.

  3. Maximum observed concentration (Cmax) of AK119 and AK104 [ Time Frame: From first dose of study drug through 30 days after last dose of study drug ]
    The endpoints for assessment of PK include serum concentrations of AK119 and AK104 at different timepoints after study drug administration.

  4. Minimum observed concentration (Cmin) of AK119 and AK104 at steady state [ Time Frame: From first dose of study drug through 30 days after last dose of study drug ]
    The endpoints for assessment of PK include serum concentrations of AK119 and AK104 at different timepoints after study drug administration.

  5. Number of subjects who develop detectable anti-drug antibodies (ADAs) [ Time Frame: From first dose of study drug through 90 days after last dose of study drug ]
    The immunogenicity of AK119 and AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has provided written informed consent
  2. Age ≥ 18 years.
  3. In dose-escalation cohorts (Phase 1a), subjects must have histologically or cytologically confirmed advanced or metastatic solid tumor that is refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available, or whereby standard therapy has been refused.
  4. In pharmacodynamic-confirmation cohorts (Phase 1a), additional enrolled subjects must have histologically or cytologically confirmed selected advanced or metastatic solid tumors, refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available. Other tumor types can be considered after discussion with the Sponsor.
  5. In dose-expansion cohorts (Phase 1b), subjects with specific tumor types will be enrolled. Subjects must have received no more than three prior lines of systemic therapy (including approved and investigational treatments) for advanced or metastatic disease. Other cohorts of different tumor types may be added based on the emerging pharmacodynamic and anti-tumor response data.
  6. Subjects must have measurable lesions according to RECIST v1.1. A previously irradiated lesion can be considered a target lesion if the lesion is measurable per RECIST v1.1, and there is objective evidence of interval increase in size since radiotherapy.
  7. For dose-escalation cohorts (Phase 1a), subjects must have available archived tumor tissue sample (block or a minimum of 10 unstained slides of formalin-fixed paraffin-embedded [FFPE] tissues) to allow for correlative biomarker studies.
  8. For pharmacodynamic-confirmation cohorts (Phase 1a) and dose-expansion cohorts (Phase 1b), subjects must be willing to provide 2 fresh biopsy samples (pre-treatment and on treatment), where clinically appropriate.
  9. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to1.
  10. Adequate organ function
  11. Life expectancy ≥12 weeks;
  12. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and within 120 days after the last dose of investigational product.
  13. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and within 120 days after the last dose of investigational product.

Exclusion Criteria:

  1. Receipt of the following treatments or procedures:

    1. Anticancer small-molecule targeted agent (e.g., tyrosine kinase inhibitor) within 2 weeks prior to the first dose of investigational product;
    2. Anti-PD-1/PD-L1 mAb within 4 weeks prior to the first dose of investigational product;
    3. Prior use of approved or investigational anti-CTLA-4 therapy, anti-CD73 therapy or adenosine 2A receptor inhibitors, or any other antibody or drug targeting T cell costimulation or immune checkpoint pathways such as ICOS, or agonists such as CD40, CD137, GITR, OX40 etc.
    4. Other anticancer mAb within 4 weeks or 5 half-lives (whichever is less) prior to the first dose of investigational product;
    5. Other anticancer therapy (e.g., chemotherapy, radiotherapy, etc.) within 4 weeks prior to the first dose of investigational product; [Note: Palliative radiotherapy > 1 week prior to first dose is allowed]
    6. Any major surgery (e.g., laparotomy, thoracotomy, removal of organ[s]) within 4 weeks prior to the first dose of investigational product;
    7. Any other non-approved investigational product or procedure within 4 weeks prior to the first dose of investigational product, or concurrent participation in another therapeutic clinical study;
  2. Any condition that required systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of investigational product.
  3. Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product; Note: seasonal vaccine for influenza which is generally inactivated is allowed.
  4. Prior organ transplantation;
  5. Prior malignancy active within the previous 3 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 cancer or carcinoma in situ of the cervix or breast;
  6. Subjects with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at Screening (based on 2 sets of brain images, performed ≥ 4 weeks apart, and obtained after the brain metastases treatment).
  7. Active infections (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to the first dose of investigational products. Note: antiviral therapy is permitted for patients with viral hepatitis;
  8. Known history of human immunodeficiency virus (HIV) infection;
  9. Known active hepatitis B or C infections (Active hepatitis B is defined as a known positive Hepatitis B surface antigen [HBsAg] result. Active hepatitis C is defined by a known positive Hepatitis C virus [HCV] antibody with detectable HCV ribonucleic acid [RNA] results);
  10. Active autoimmune diseases or history of autoimmune diseases that may relapse. Note: Subjects with controlled type 1 diabetes mellitus, thyroiditis in euthyroid state or hypothyroidism well managed by hormone replacement therapy (HRT), or skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis) are eligible;
  11. History of interstitial lung disease, noninfectious pneumonitis except for those induced by radiation therapies;
  12. Uncontrolled massive ascites or pleural effusion, as determined by the Investigator;
  13. Patients with clinically significant cardio-cerebrovascular disease.
  14. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec calculated from 3 ECGs (within 5 minutes at least 1 minute apart);
  15. Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, uncontrolled endocrinopathy, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent;
  16. History of severe hypersensitivity reactions to other mAbs;
  17. Toxicities of prior anticancer therapy have not resolved to NCI-CTCAE version 5.0 Grade ≤1, or to levels dictated in the inclusion/exclusion criteria, except toxicities not considered a safety risk (e.g., alopecia, neuropathy, or asymptomatic laboratory abnormalities);
  18. Pregnant or breastfeeding women;
  19. Any other conditions that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04572152


Contacts
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Contact: Kon Yew Kwek +86 (0760) 8987 3999 global.trials@akesobio.com

Locations
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Australia, New South Wales
Blacktown Cancer and Haematology Centre (Blacktown Hospital)
Blacktown, New South Wales, Australia, 2148
Contact: Raymond TANGUNAN       raymond.tangunan@health.nsw.gov.au   
Contact: Amanda BRYANT       amanda.bryant1@health.nsw.gov.au   
Principal Investigator: Matteo CARLINO, MBBS PHD         
Australia, Queensland
ICON Cancer Centre
South Brisbane, Queensland, Australia, 4101
Contact: Adam STONELEY       adam.stoneley@icon.team   
Contact: Jane HOLT       jane.holt@icon.team   
Principal Investigator: Jim COWARD, MBBS, MRCP (UK), FR         
Australia, South Australia
Ashford Cancer Centre
Adelaide, South Australia, Australia, 5037
Contact: Sue YEEND       syeend@adelaidecancercentre.com.au   
Contact: Tanya DAYMAN       tdayman@adelaidecancercentre.com.au   
Principal Investigator: Amy HSIEH, MBBS FRACP         
Australia, Victoria
Monash Health
Clayton, Victoria, Australia, 3168
Contact: Penny MACQUIRE       Penelope.Macquire@monashhealth.org   
Contact: Kelly HOFFMAN         
Principal Investigator: Sophia FRENTZAS, MBBS PHD         
Alfred Health (The Alfred Hospital)
Melbourne, Victoria, Australia, 3004
Contact: Cheryl-Ann HAWKINS       N.Cross@alfred.org.au   
Principal Investigator: Benjamin MARKMAN, MBBS (HONS) FRACP         
Sponsors and Collaborators
Akeso
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Responsible Party: Akeso
ClinicalTrials.gov Identifier: NCT04572152    
Other Study ID Numbers: AK119-102
First Posted: October 1, 2020    Key Record Dates
Last Update Posted: October 1, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Akeso:
Anti CD73
PD-1/ CTLA-4
Bispecific
Additional relevant MeSH terms:
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Neoplasms