A Phase III Clinical Study Comparing JS004 Plus Toripalimab With Investigator-Selected Chemotherapy in Patients With PD-(L)1monoclonal Antibody Refractory Classic Hodgkin Lymphoma (cHL)

Study Overview
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Brief Summary
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The study is being conducted to compare JS004 plus Toripalimab with Investigator-Selected Chemotherapy in Patients with PD-(L)1 monoclonal antibody refractory Classic Hodgkin Lymphoma (cHL)

Detailed Description
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The study is a randomized, open-label, phase III clinical trial. The main objective is to compare the efficacy of JS004 plus Toripalimab with Investigator-Selected Chemotherapy in treating patients with PD-(L)1 monoclonal antibody refractory Classic Hodgkin Lymphoma (cHL). The study will assess the safety and tolerability of JS004 combined with Toripalimab.

Official Title
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A Phase III, Randomised, Open-label,, Multi-Center Clinical Study Comparing JS004 Plus Toripalimab With Investigator-Selected Chemotherapy in Patients With PD-(L)1 Monoclonal Antibody Refractory Classic Hodgkin Lymphoma (cHL)

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Biological: JS004 in combination with Toripalimab
* Drug: Bendamustine or gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet all of the following inclusion criteria to be enrolled: Age at least 18 years old, both males and females are eligible Pathologically confirmed classical Hodgkin Lymphoma (cHL) with either relapsed (disease progression after achieving CR/PR in recent treatment) or refractory (failure to achieve CR/PR in recent treatment) status. Has exhausted all standard treatment and refractory to PD-(L)1 monoclonal antibody (mAb) ECOG: 0-2 At least one measurable lesion meeting the criteria specified in the Lugano 2014 response assessment. Exclusion Criteria: Known allergy or contraindication to the investigational drug or its components Permanent discontinuation of anti-PD-(L)1 antibody due to immune-related adverse reactions. Presence of central nervous system (CNS) metastasis. Presence of pleural effusion, ascites, or pericardial effusion requiring intervention (e.g., aspiration, drainage) Active autoimmune diseases requiring systemic treatment (such as corticosteroids or immunosuppressive drugs) within the past 2 years

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JS004 plus Toripalimab<br>JS004 200mg plus Toripalimab 240mg IV on day 1 of each cycle, every 3 weeks for up to 2 years | Biological: JS004 in combination with Toripalimab<br>* Participants will receive JS004 in combination with Toripalimab (200 mg/240 mg) by intravenous (IV) infusion on Day 1, then every three weeks (Q3W), for up to 35 infusions.<br>|
| Active Comparator: Investigator-Selected Chemotherapy<br>Bendamustine or gemcitabine | Drug: Bendamustine or gemcitabine<br>* Participants will receive Investigator-Selected chemotherapy of EITHER bendamustine by IV infusion at a dose of 90 or 120 mg/m^2 on Day 1 and Day 2 of either a 3- or 4-week cycle for up to 6 cycles OR gemcitabine by IV infusion at a dose of 1000 mg/m^2 on Day 1 and Day 8 of a 3-week cycle for up to 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) per Lugano criteria 2014 as Assessed by Independent review committee (IRC) | PFS is defined as the time from randomization to the first documented disease progression per Lugano criteria 2014 as assessed by IRC or death due to any cause, whichever occurs first. | Up to approximately 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to approximately 45 months | 
| Progression Free Survival (PFS) per Lugano criteria 2014 Assessed by Investigator | PFS is defined as the time from randomization to the first documented disease progression per Lugano criteria 2014 assessed by Investigator or death due to any cause, whichever occurs first. | Up to approximately 36 months | 
| Objective Response Rate (ORR) per Lugano criteria 2014 Assessed by Investigator | ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano criteria 2014 assessed by Investigator | Up to approximately 36 months | 
| Complete response rate (CRR) per Lugano criteria 2014 Assessed by Investigator | Complete response rate (CRR) is defined as the proportion of subjects in which BoR is CR, best overall response (BoR) refers to the best response as determined by the investigator. | Up to approximately 36 months | 
| Duration of Response (DOR) per Lugano Response Criteria as Assessed by Investigator | For participants who demonstrate CR or PR per Lugano criteria 2014 as assessed by Investigator, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. | Up to approximately 36 months | 
| Incidence and severity of all adverse events (AE) that occurred during the clinical trial | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number and sverity of participants who experience an AE will be presented. | Up to approximately 36 months | 
| Pharmacokinetics | To characterize the trough concentrations of JS004 and toripalimab; | Up to approximately 36 months | 
| Immunogenicity profiles | To characterize incidence and titer of antidrug antibodies (ADA) and/or neutralizing antibodies (Nab); | Up to approximately 36 months |