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Phase 1, Dose Escalation and Dose Expansion Study of AK117, a CD47-targeting Antibody

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. Identifier: NCT04349969
Recruitment Status : Not yet recruiting
First Posted : April 16, 2020
Last Update Posted : April 16, 2020
Akesobio Australia Pty Ltd
Information provided by (Responsible Party):

Brief Summary:
This is a first-in-human, Phase 1, multicenter, open label, single arm, integrated 3-part dose escalation and dose expansion study designed to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK117 administered intravenously to adult subjects with relapsed/refractory advanced or metastatic solid tumors or lymphomas.

Condition or disease Intervention/treatment Phase
Neoplasms Malignant Drug: AK117 Phase 1

Detailed Description:
The study comprises 3 parts: a dose escalation phase for estimating the optimal priming dose (Part A), a dose escalation phase for estimating the optimal maintenance dose (Part B), and a dose expansion phase (Part C). The 3 parts will be conducted sequentially. Approximately 159 subjects (up to 27 subjects in Part A, up to 72 subjects in Part B, and up to approximately 60 subjects in Part C) will be enrolled in this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 159 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 in Subjects With Relapsed/Refractory Advanced or Metastatic Solid Tumors or Lymphomas
Estimated Study Start Date : April 25, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment
AK117 monotherapy
Drug: AK117
An intravenous (IV) infusion of AK117 as monotherapy. All subjects will receive 4 weekly infusions (Days 1, 8, 15, and 22) of AK117 in each 28-day treatment cycle until unacceptable toxicity, documentation of confirmed progressive disease (PD), or subject withdrawal

Primary Outcome Measures :
  1. Number of participants with adverse events (AEs) [ Time Frame: From the time of informed consent signed through 30 days after the last dose of AK117 ]
    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 4 weeks ]
    DLTs will be assessed during the first 4 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 cycle (4 weeks) of treatment.

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    ORR defined as the proportion of subjects who achieves a best overall response of CR or PR, assessed by Investigator per RECIST Version 1.1 for solid tumor or the Lugano 2014 Classification for lymphoma

  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).

  3. Maximum observed concentration (Cmax) of AK117 [ Time Frame: From first dose of AK117 through to 30 days after last dose of AK117 ]
    The endpoints for assessment of PK of AK104 include serum concentrations of AK117 at different timepoints after AK117 administration.

  4. Minimum observed concentration (Cmin) of AK117 at steady state [ Time Frame: From first dose of AK117 through to 30 days after last dose of AK117 ]
    The endpoints for assessment of PK of AK104 include serum concentrations of AK117 at different timepoints after AK117 administration.

  5. Number of subjects who develop detectable anti-drug antibodies (ADAs) [ Time Frame: From first dose of AK117 through to 30 days after last dose of AK117 ]
    The immunogenicity of AK117 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

All Subjects

  1. Able to provide written and signed informed consent and any locally required authorization obtained from the subject/legal representative, which must be obtained prior to performing any protocol related procedures, including screening evaluations.
  2. Men or women aged ≥18 years at the time of study entry.
  3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
  4. Life expectancy ≥12 weeks.
  5. Female subjects are eligible to participate if at least 1 of following conditions applies:For a woman of childbearing potential (WOCBP) who is sexually active with a non sterilized male partner: must have a negative pregnancy test at the Screening Visit (within 3 days prior to the first dose of the investigational product), should not be lactating, and must agree to use 2 methods of contraception up to 120 days after the last dose of investigational product; Is a woman of non childbearing potential.
  6. Non sterilized male subjects who are sexually active with female partners of childbearing potential must agree to use contraception up to 120 days after the last dose of investigational product.
  7. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures as specified in the protocol.
  8. Willing to receive blood transfusion(s) when so advised by the investigator. Subjects with Solid Tumors (Parts A, B, and C)
  9. Subjects must have a histologically or cytologically confirmed advanced solid tumor that is refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available.
  10. Subject must have at least 1 measurable lesion according to RECIST v1.1. A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per RECIST v1.1, and there is objective evidence of interval increase in size since radiotherapy.
  11. Adequate organ function. Subjects with Lymphomas (Part B cohort expansion and Part C)
  12. Subjects must have histologically confirmed non-Hodgkin lymphoma (NHL), which may include transformed lymphoma, relapsed or refractory to autologous hematopoietic stem cell transplantation, or at least 2 lines of prior chemotherapy.
  13. Subjects must have disease that is measurable or assessable for response as per Lugano Classification 2014.
  14. Adequate organ function.

Exclusion Criteria:

All Subjects

  1. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow up period of an interventional study.
  2. 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 skin cancer, or carcinoma in situ of the cervix or breast.
  3. Active brain/central nervous system (CNS) metastases (defined as neurologically stable for <4 weeks and/or symptomatic and/or requiring treatment with steroids and/or leptomeningeal disease).
  4. Active infections (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to the first dose of investigational product.
  5. Known history of testing positive for human immunodeficiency virus (HIV) or known active acquired immunodeficiency syndrome.
  6. 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).
  7. Active or prior documented autoimmune disease that may relapse.
  8. History of interstitial lung disease or noninfectious pneumonitis, except for those induced by radiation therapies.
  9. History of hemolytic anemia of any cause (including Evans syndrome) within 3 months prior to the first dose of investigational product.
  10. History of defects in RBC production, or hemoglobin production or metabolism (eg, glucose 6 phosphate dehydrogenase deficiency, thalassemia, sickle cell disease, hereditary spherocytosis).
  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 hemophagocytic lymphohistiocytosis.
  14. History of severe hypersensitivity reactions to other mAbs.
  15. History of organ transplantation.
  16. Known allergy or reaction to any component of the investigational product formulation.
  17. Receipt of the following treatments or procedures: Any anticancer therapy targeting the CD47/SIRPα signaling axis; Anticancer small molecule targeted agent within 2 weeks prior to the first dose of investigational product; Anticancer mAbs within 6 weeks prior to the first dose of investigational product or 5 half lives (whichever is lesser); Other anticancer therapy (eg, chemotherapy, radiotherapy, etc) within 4 weeks prior to the first dose of investigational product.
  18. 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.
  19. Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product.

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 identifier (NCT number): NCT04349969

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Contact: Kon Yew Kwek, MD +86 (0760) 8987 3999

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Australia, New South Wales
Blacktown Hospital
Sydney, New South Wales, Australia
Contact: Adnan Nagrial         
Principal Investigator: Adnan Nagrial, MBBS         
Australia, Queensland
ICON Cancer Foundation
South Brisbane, Queensland, Australia, 4101
Contact    +61 3737 4500      
Principal Investigator: Jermain Coward, MBBS         
Australia, South Australia
Adelaide Cancer Centre
Kurralta Park, South Australia, Australia, 5037
Contact    +61 8 8292 2220      
Principal Investigator: Anna Mislang, MBBS         
Australia, Victoria
Austin Health
Heidelberg, Victoria, Australia, 3084
Contact    +61 (03) 9496 5354      
Principal Investigator: Hui Gan, MBBS         
Australia, Western Australia
Linear Clinical Research/Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Contact    +61 (0) 8 6382 5100      
Principal Investigator: Michael Millward, MBBS         
Sponsors and Collaborators
Akesobio Australia Pty Ltd
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Responsible Party: Akeso Identifier: NCT04349969    
Other Study ID Numbers: AK117-101
First Posted: April 16, 2020    Key Record Dates
Last Update Posted: April 16, 2020
Last Verified: April 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:
Antineoplastic Agents, Immunological
Additional relevant MeSH terms:
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