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

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

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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).

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Kon Yew Kwek, MD; +86 (0760) 8987 3999; clinicaltrials@akesobio.com

Locations

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

Akeso

Akesobio Australia Pty Ltd

More Information

• Responsible Party: Akeso
• ClinicalTrials.gov Identifier: NCT04349969
• Other Study ID Numbers: AK117-101
• First Posted: April 16, 2020
• Last Update Posted: April 16, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Neoplasms