A Study of PD-1/CTLA-4 Bispecific AK104 in Relapsed or Refractory Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of AK104，an anti- PD-1 and CTLA-4 bispecific antibody, in subjects with relapsed or refractory peripheral T cell lymphoma. The subject will receive AK104 450mg Q2W until unacceptable toxicity, confirmed disease progression, withdrawal of consent, or for a maximum of 24 months.

Official Title
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A Multicenter, Open-label, Phase Ib/II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Subjects With Relapsed or Refractory Peripheral T Cell Lymphoma

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Biological: AK104


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically confirmed advanced Peripheral T-cell lymphoma. Relapsed or refractory disease after at least 1 prior systemic treatment for the primary malignancy and not a candidate for other curative treatments. Eastern Cooperative Oncology Group (ECOG) physical fitness score is 0 or 1. Adequate organ functions Effective methods of contraception. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments. Exclusion Criteria: Patients diagnosed as adult T cell lymphoma / leukemia (ATLL). Any prior exposure to PD-1/PD-L1、CTLA-4 targeting agents. Previous allogeneic stem cell transplant within 3 months prior to enrolment, active graft vs host disease (GVHD), or requiring transplant-related immunosuppression. Serious systemic infections or local infections during the 2 months before screening. History of cancer in 5 years before screening., including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved). Have a known allergy or hypersensitivity to any biologic therapy at screening that would pose an unacceptable risk to the subject if participating in this study. Has enrolled in any other trials during 3 months prior to screening or concurrently enrolled in any other trials. Received allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. Subjects who received immunomodulatory drugs in 4 weeks before screening, including thymosin, interferon and interleukin, et al. Patients who received radiotherapy, chemotherapy, targeted therapy (except TKI), immunotherapy within 4 weeks before screening, and patients who received TKI drugs within 2 weeks before screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK104<br>AK104 450mg IV every 2 weeks (Q2W) | Biological: AK104<br>* The subjects will receive AK104 till disease progression or for a maximum of 24 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response is defined as the proportion of subjects with confirmed CR or PR according to the Lugano 2014 classification for lymphoma, assessed by the investigator. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first. | Up to 2 years | 
| Disease control rate (DCR) | The DCR is defined as the proportion of subjects with CR, PR, or SD according to the Lugano 2014 classification for lymphoma. | Up to 2 years | 
| Duration of response (DoR) | Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first. | Up to 2 years | 
| Number of subjects experiencing adverse events (AEs) | The incidence and severity of adverse events, containing clinically significant abnormal laboratory tests, vital signs and electrocardiogram (ECG) results. | From the time of informed consent signed through 90 days after the last dose of AK104 | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs). | From first dose of AK104 through 90 days after last dose of AK104 | 
| Observed concentrations of AK104 | The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration. | From first dose of AK104 through 90 days after last dose of AK104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-PD-1, Anti-CTLA-4, Bispecific