A Study of AK129 With or Without AK117 in PD(L)1-refractory Classic Hodgkin Lymphoma

A Phase I/II Study of AK129 (Bispecific Antibody Targeting LAG-3 and PD-1) Monotherapy or in Combination With AK117 (Anti-CD47 Monoclonal Antibody) in Relapse or Refractory Classic Hodgkin Lymphoma With PD-1/L1 Inhibitor Treatment Failure

This is a phase I/II study. All subjects are patients diagnosed with relapse or refractory (R/R) classic Hodgkin lymphoma (cHL) and has progressed on treatment with PD-1/L1 inhibitor therapy. The purpose of this study is to evaluate the safety and efficacy of AK129 (bispecific antibody targeting LAG-3 and PD-1) monotherapy or in combination with AK117 (anti-CD47 monoclonal antibody) in R/R cHL with PD-1/L1 inhibitor treatment failure.

Study Overview

• Status: Recruiting
• Conditions: Classic Hodgkin Lymphoma
• Intervention / Treatment: Drug: AK117; Drug: AK129

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Wenting Li, MD; Phone Number: +86(0760)89873999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Contact: Yuqin Song

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old at the time of enrolment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected Survival of ≥ 12 weeks.
• Diagnosed as R/R cHL according to Lugano 2014 criteria.
• Has progressed on treatment with PD-1/L1 inhibitior therapy.
• Has adequate organ function.
• All female and male subjects of reproductive potential must agree to use an effective method of contraception from the start of screening until 120 days after the last dose of study treatment.

Exclusion Criteria:

• Diagnosed with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) or gray zone lymphoma.
• Central nervous system (CNS) lymphoma involvement.
• Known history of human T-cell leukemia virus type 1 (HTLV-1) infection.
• Autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor T cell immunotherapy (CAR-T) within 90 days prior to the first dose of study treatment.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• Previous use of any agents targeting the CD47-SIRPα pathway, LAG-3 pathway, or similar targets.
• Has other malignancies within 3 years prior to the first dose or residual lesions from other malignancies diagnosed more than 3 years ago.
• Has an active autoimmune disease requiring systemic treatment within 2 years prior to the first dose.
• History of active or previously confirmed inflammatory bowel disease.
• History of interstitial lung disease requiring corticosteroid therapy, or current interstitial lung disease.
• Has known active Hepatitis B or Hepatitis C.
• Unresolved toxicity from previous anti-tumor treatment.
• Uncontrolled comorbidities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK129; Phase Ia: Subjects will receive AK129: different doses on every 2 weeks.	Drug: AK129; Subjects receive AK129 intravenously.
Experimental: AK129+AK117; Phase Ib: Subjects will receive: AK129: different doses on every 2 weeks, AK117: 30mg/kg on every 2 weeks. Phase II: Subjects will receive: AK129: recommended phase II dose (RP2D) from phase Ib on every 2 weeks, AK117: 30mg/kg on every 2 weeks.	Drug: AK117; Subjects receive AK117 intravenously.; Drug: AK129; Subjects receive AK129 intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Number of participants with dose limiting toxicity (DLT)	Any untoward medical occurrence in a subject within the first 28 days following the first dose, considered related to the study treatment.	Within the first 28 days following the first dose of study treatment.
Phase I/II: Incidence and severity of adverse events (AEs)	Any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to approximately 2 years.
Phase I/II: Objective response rate (ORR)	The proportion of subjects achieving complete response (CR) or partial response (PR) assessed by investigator per Lugano 2014 criteria.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	The proportion of subjects achieving complete response (CR) , partial response (PR) or stable disease (SD) assessed by investigator per Lugano 2014 criteria.	Up to approximately 2 years
Time to response (TTR)	The time from cycle 1 day 1(C1D1) to the first recorded response assessed by investigator per Lugano 2014 criteria.	Up to approximately 2 years
Duration of response (DoR)	The time from the first recorded response until disease progression assessed by investigator or death due to any cause, whichever occurs first.	Up to approximately 2 years
Progression-free survival (PFS)	The time from C1D1 until disease progression assessed by investigator or death due to any cause, whichever occurs first.	Up to approximately 2 years
Overall survival (OS)	The time from C1D1 until death due to any cause.	Up to approximately 2 years
Maximum concentration (Cmax)	The maximum concentration of the drug observed in the blood plasma after administration.	Up to approximately 2 years
Time to maximum concentration (Tmax)	The time taken to reach the maximum concentration (Cmax) of the drug in the blood plasma.	Up to approximately 2 years
Area under the curve (AUC)	The area under the plasma concentration versus time curve, which represents the total drug exposure over time.	Up to approximately 2 years
Half-life (T1/2)	The time required for the plasma concentration of the drug to decrease by half.	Up to approximately 2 years
Anti-drug antibody (ADA)	Number of subjects with detectable anti-drug antibodies.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Study Director: Wenting Li, MD, Akeso

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: September 26, 2024
• First Submitted That Met QC Criteria: October 12, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 9, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease
• Other Study ID Numbers: AK129-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No