A Study of Zimberelimab(GLS-010) Combined With AVD for Newly Diagnosed Early-stage Hodgkin's Lymphoma

Phase 2

Recruiting

• Conditions: Classical Hodgkin Lymphoma
• Interventions: Drug: Zimberelimab 240mg

• Registration Number: NCT05900765
• Lead Sponsor: Sun Yat-sen University

Brief Summary

This is a multicenter, open-label single-arm phase II study to evaluate the efficacy and safety of Zimberelimab (GLS-010) combined with AVD for newly diagnosed early-stage Hodgkin's lymphoma under the guidance of PET/CT.

Detailed Description

Despite achieving good disease control and long-term survival rates for over 80% of classical Hodgkin lymphoma (cHL) patients who receive first-line therapy, approximately 10% of early-stage and 30% of advanced cHL patients experience disease relapse or refractoriness after initial treatment, and only half of the patients can be cured through high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). Meanwhile, the current standard first-line treatment still centers around conventional chemotherapy with cytotoxic agents. As such, the clinical challenge of cHL first-line treatment lies in striking a balance between efficacy and toxicity, and developing low-toxicity, high-efficiency treatment strategies to achieve the optimal treatment goal of maximizing efficacy while minimizing short- and long-term toxicities.

Study Timeline

• Status Verified: 2023-06
• Study First Submitted: 2023-06-02
• Study First Submitted QC: 2023-06-12
• Study First Posted: 2023-06-13
• Study Start: 2023-06-14
• Last Update Submitted: 2023-06-15
• Last Update Posted: 2023-06-18
• Primary Completion: 2025-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

1. Diagnosed with primary classical Hodgkin lymphoma (HL) based on histopathology.
2. Stage I-II .
3. At least one measurable target lesion（Lugano 2014）.
4. Age 18 years or older (including 18 years) to 45 years (recent fertility requirements and concern about chemotherapy side effects), or age >60 years (older patients who are frail and unwilling to undergo chemotherapy), male or female.
5. ECOG PS 0-3,
6. Expected survival ≥ 3 months.

Exclusion Criteria

1. Hodgkin's lymphoma with nodular lymphocyte predominant type.
2. Patients who are scheduled to undergo subsequent autologous stem cell transplantation.
3. Contraindications to radiotherapy.
4. With central nervous system (meningeal or parenchymal) involvement.
5. Contraindications to immune checkpoint inhibitors.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Zimberelimab combined with or without AVD sequential radiotherapy	Zimberelimab 240mg	1. Combination therapy： Subjects received Zimberelimab 240mg Q3W 2 cycle. According to the results of PET/CT evaluation: CR: Additional 2 cycles of Zimberelimab (4 cycles of Zimberelimab monotherapy in total); PR: 2 cycles of Zimberelimab+ AVD therapy (only PR patients combined with AVD). Subjects who did not achieve a Partial Response (PR) or Complete Response (CR) in their initial or subsequent efficacy evaluations, and whose potential for benefit was deemed unlikely by the investigator, were discontinued from the study. 2. Radiotherapy treatment period (patients with CR/PR): Sequentially radiation therapy 20-30Gy.

Primary Outcome Measures

Name	Time	Method
Complete response rate (CRR) after 2 cycles	Up to approximately 2 months	Percentage of the sum of the number of patients in complete remission (CR), complete remission without confirmation (CRu) to the total number of patients in the full analysis set

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to approximately 2 years	Overall survival (OS) is defined as the time from the first dose of investigational products until death due to any cause
Incidence and severity of adverse events(AEs)	Up to approximately 2 years	Incidence and severity of AEs is aim to evaluate the safety of Zimberelimab(GLS-010) Combined With AVD
Objective response rate (ORR) after 4 cycles ( Lugano2014)	Up to approximately 2 years	ORR is proportion of subjects with complete response(CR) or partial response(PR)
Complete response rate (CRR) after 4 cycles ( Lugano2014)	Up to approximately 2 years	Percentage of the sum of the number of patients in complete remission (CR), complete remission without confirmation (CRu) to the total number of patients in the full analysis set
Total ORR and CRR after Zimberelimab treatment + radiotherapy	Up to approximately 2 years	ORR is proportion of subjects with complete response(CR) or partial response(PR); Percentage of the sum of the number of patients in complete remission (CR), complete remission without confirmation (CRu) to the total number of patients in the full analysis set
Duration of response (DOR)	Up to approximately 2 years	Duration of response (DoR) is defined as the period from the first documentation of confirmed response (CR or PR) to the first documentation of progressive disease(PD) or death due to any cause, whichever occurs first
Progression-free survival time (PFS)	Up to approximately 2 years	Progression-free survival (PFS) is defined as the time from the first dose of investigational products until documentation of PD or death due to any cause, whichever occurs first

Trial Locations

Locations (1)

Department of Medical Oncology, Sun Yat-Sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China