A Phase 1 Dose Escalation and Expansion Study of AK117

Phase 1

Completed

• Conditions: Neoplasms Malignant
• Interventions: Drug: AK117

• Registration Number: NCT04728334
• Lead Sponsor: Akeso

Brief Summary

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

Detailed Description

The study comprises a dose escalation phase and a dose expansion phase. The phases will be conducted sequentially. Approximately 162 subjects will be enrolled in this study.

Study Timeline

• Study First Submitted: 2021-01-24
• Study First Submitted QC: 2021-01-24
• Study First Posted: 2021-01-28
• Study Start: 2021-03-23
• Primary Completion: 2022-01-25
• Study Completion: 2023-05-12
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-28
• Last Update Posted: 2025-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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.
  2. Men or women aged ≥18 years and ≤75 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. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures as specified in the protocol.
  6. Subjects must provide the tumor tissue samples after the diagnosis of solid tumor or lymphoma.
  7. Adequate organ function.
  8. Subjects with Solid Tumors：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. Subject must have at least 1 measurable lesion according to RECIST v1.1.
  9. Subjects with Lymphomas：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. Subjects must have disease that is measurable or assessable for response as per Lugano Classification 2014.

Exclusion Criteria

• All Subjects

  1. Concurrent enrollment in another clinical study, unless it is an observational 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.
  3. Receipt: The last cycle of anticancer therapy within 3 weeks prior to the first dose of investigational product; Anticancer small molecule targeted agent, palliative local treatment for non-target lesions, non-specific immunomodulatory therapy within 2 weeks prior to the first dose of investigational product; Chinese medicines with anti-tumor indications within 1 week prior to the first dose of investigational product; Any major surgery within 4 weeks; RBC infusion within 3 months.
  4. Metastasis or infiltration of brainstem and meninges;Metastasis or compression of the spinal cord; Active brain/central nervous system (CNS) metastases.
  5. Subjects with clinical symptoms or repeated drainage of pleural effusion, pericardial effusion or ascites.
  6. Cancer invasion of important surrounding organs or risk of esophageal tracheal fistula or esophageal pleural fistula.
  7. Known history of testing positive for human immunodeficiency virus (HIV) or known active acquired immunodeficiency syndrome.
  8. Known active hepatitis B or C infections (known positive HBsAg result or positive HCV antibody with detectable HCV ribonucleic acid [RNA] results).
  9. Active or prior documented autoimmune disease that may relapse.
  10. History of interstitial lung disease or noninfectious pneumonitis, except for those induced by radiation therapies.
  11. History of hemolytic anemia of any cause within 3 months prior to the first dose of investigational product.
  12. History of defects in RBC production, or hemoglobin production or metabolism.History of hemophagocytic lymphohistiocytosis.
  13. Previous or current gastrointestinal perforation, surgical incision, wound healing complications and bleeding events.
  14. Patients with clinically significant cardio-cerebrovascular disease.
  15. 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.
  16. Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to the first dose of investigational product.
  17. Subjects with prior use of anti-PD-1, anti-PD-L1, anti-CTLA-4, or any other immuno-oncology agents, receipt of the following treatments or procedures: Use of immunotherapy or IO drug within 21 days prior to the first dose; Subjects had an irAE that resulted in permanent discontinuation of previous immunotherapy; Subjects had a history of grade 3 or higher irAE or cardiac, neurological, or ocular irAE of any grade at the time of prior immunotherapy; Prior to screening in this study, all AEs at the time of previous immunotherapy had not been completely remission or remission to grade 1; Subjects need to use other immunosuppressants other than glucocorticoids systematically to treat irAE.
  18. History of severe hypersensitivity reactions to other mAbs.
  19. History of organ transplantation.
  20. Known allergy or reaction to any component of the investigational product formulation.
  21. Receipt any anticancer therapy targeting the CD47/SIRPα signaling axis.
  22. Known history of mental illness, alcohol or drug abuse.
  23. Existing uncontrolled comorbiditions; Or a mental illness/social condition that may limit the subject's compliance with study requirements or affect the subject's ability to provide written informed consent.
  24. Other exclusion criteria for subjects with lymphoma:History of HTLV-1 infection.Subjects with primary or secondary central nervous system lymphoma. Subjects with history of allogeneic hematopoietic stem cell transplantation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AK117 monotherapy	AK117	AK117 monotherapy intravenous (IV) infusion - Weekly doses

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events (AEs)	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.
Number of participants with a Dose Limiting Toxicity (DLT)	During the first 21 days	DLTs will be assessed during the first 21 days 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 .

Secondary Outcome Measures

Name	Time	Method
Disease control rate (DCR)	Up to 2 years	The DCR is defined as the proportion of subjects with CR, PR, or SD .
Maximum observed concentration (Cmax) of AK117	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.
Objective response rate (ORR)	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
Minimum observed concentration (Cmin) of AK117 at steady state	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.
Number of subjects who develop detectable anti-drug antibodies (ADAs)	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 antidrug antibodies (ADAs).

Trial Locations

Locations (1)

FuDan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China