Tislelizumab in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (TIRHOL)

A Phase 2, Multicenter, Open-Label Study of Tislelizumab (BGB-A317) in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

This was a Phase 2 trial evaluating the effectiveness and safety of tislelizumab in participants with relapsed or hard-to-treat classical Hodgkin lymphoma (cHL). Participants were grouped by prior treatments. The main outcome was to assess overall response rate (ORR) across both cohorts. Participants continued receiving the study treatment until their disease got worse, side effects became too severe, or they chose to stop for other reasons.

Study Overview

• Status: Completed
• Conditions: Classical Hodgkin Lymphoma
• Intervention / Treatment: Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, VIC 3168
      • Monash Health
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-2013
      • Barbara Ann Karmanos Cancer Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37920-1511
      • University of Tennessee Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Participants had a histologically confirmed diagnosis of relapsed or refractory classical Hodgkin lymphoma (cHL).

2. Participants had either:

   • Relapsed cHL, defined as disease progression after a partial response (PR) or complete response (CR) to their most recent therapy; or
   • Refractory cHL, defined as failure to achieve PR or CR to their most recent therapy.

   Participants were assigned to one of two cohorts based on the following:

   Cohort 1: Participants who were relapsed or refractory after prior autologous hematopoietic stem cell transplantation (HSCT):

   1. Had failed to achieve a response or had experienced disease progression following autologous HSCT (a transplant using the participant's own stem cells).
   2. Were not considered candidates for additional autologous or allogeneic HSCT (a transplant using donor stem cells).

   Cohort 2: Participants who were relapsed or refractory to salvage chemotherapy and had not received prior HSCT:

   1. Were not considered candidates for autologous or allogeneic HSCT.
   2. Had received at least one prior systemic therapy regimen for cHL.
3. Participants had measurable disease, defined as at least one positron emission tomography (PET)-positive, 2-\[18F] fluoro-2-deoxy-D-glucose (FDG)-avid nodal lesion greater than 1.5 centimeters (cm) in longest diameter, or at least one FDG-avid extranodal lesion (hepatic nodule) greater than 1.0 cm in longest diameter.
4. Participants had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, indicating full activity or restricted activity but capable of self-care.

Key Exclusion Criteria:

1. Participants had nodular lymphocyte-predominant Hodgkin lymphoma or gray zone lymphoma.
2. Participants had received prior allogeneic HSCT.
3. Participants had received prior therapy targeting immune checkpoint pathways, including programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
4. Participants had active autoimmune disease or a history of autoimmune disease with potential to relapse.

Note: Additional inclusion and exclusion criteria defined in the protocol may have applied.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants who had relapsed or refractory classical Hodgkin lymphoma and had either not achieved a response or had disease progression following autologous hematopoietic stem cell transplantation received tislelizumab 200 milligrams (mg) intravenously every 3 weeks.	Drug: Tislelizumab; 200 milligrams (mg) intravenously every 3 weeks (Q3W); Other Names: BGB-A317
Experimental: Cohort 2; Participants who had relapsed or refractory classical Hodgkin lymphoma and had either not achieved a response or had disease progression after at least one prior systemic therapy and were not candidates for autologous or allogeneic hematopoietic stem cell transplantation received tislelizumab 200 mg intravenously every 3 weeks.	Drug: Tislelizumab; 200 milligrams (mg) intravenously every 3 weeks (Q3W); Other Names: BGB-A317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) by Positron Emission Tomography (PET) and Computed Tomography (CT) per the Lugano Classification and as determined by the investigator. CR was defined as the complete disappearance of all target lesions on PET-CT, with no new lesions detected. PR was defined as a significant reduction in metabolic activity or lesion size consistent with partial tumor shrinkage as per Lugano criteria.	From first dose to primary analysis data cutoff (12 Dec 2022) or new anti-lymphoma therapy start, whichever came first. Median follow-up was 11.4 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate (CRR)	CRR was defined as the percentage of participants who achieved a best overall response of complete response (CR) by PET-CT or CT per the Lugano Classification and determined by the investigator. CR was defined as the complete disappearance of all target lesions on PET-CT or CT, with no new lesions detected.	From first dose to primary analysis data cutoff (12 Dec 2022) or new anti-lymphoma therapy start, whichever came first. Median follow-up was 11.4 months.
Duration of Response (DOR)	DOR was defined as the time from the date that response criteria (CR or PR) were first met to the date of objectively documented disease progression or death, whichever occurred first. Participants without an event were censored at the data cutoff or end of study, whichever occurred first. Participants who received new anti-lymphoma therapies, including Hematopoietic Stem Cell Transplantation (HSCT), before having an event were censored at the date of therapy initiation. Only participants with confirmed response were included in the analysis. Median DOR was estimated using the Kaplan-Meier method.	From first dose to primary analysis data cutoff (12 Dec 2022) or new anti-lymphoma therapy start, whichever came first. Median follow-up was 11.4 months.
Time to Response (TTR)	TRR was defined as the time from the date of the first dose of tislelizumab to the date the response criteria were first met CR or PR per the Lugano Classification, and was analyzed only in participants who achieved an overall response; CR was defined as complete disappearance of disease, PR as ≥50% reduction in tumor burden, and Overall Response Rate (ORR) included participants with either CR or PR.	From first dose to primary analysis data cutoff (12 Dec 2022) or new anti-lymphoma therapy start, whichever came first. Median follow-up was 11.4 months.
Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Treatment-emergent adverse events (TEAEs) were defined as any AE that began or worsened in severity after the first dose of study treatment and up to 90 days following the last dose, regardless of initiation of new anti-lymphoma therapy. The following safety data are reported: Number of participants with any TEAEs: Participants who experienced at least one TEAE of any grade. Number of participants with any Grade ≥3 TEAEs: Participants who experienced at least one TEAE that was Grade 3 or higher in severity. Number of participants with any SAEs: Participants who experienced at least one serious adverse event, regardless of relationship to study treatment, occurring up to 90 days after the last dose.	From the date of the first dose of tislelizumab through 90 days after the last dose (maximum duration of tislelizumab exposure was 168 weeks)

Collaborators and Investigators

• Sponsor: BeiGene
• Collaborators: Lymphoma Study Association
• Investigators: Principal Investigator: Herve Ghesguieres, Lymphoma Study Association

Publications and helpful links

General Publications

• Ghesquières H, López-Guillermo A, De la Cruz F, et al. Tislelizumab, an anti-PD-1 antibody, in patients with relapsed/refractory classical Hodgkin lymphoma in TIRHOL BGB-A317-210: a prospective multicenter LYSA phase 2 study conducted in Western countries. Blood. 2023;142(Suppl 1):1717. DOI:10.1182/blood-2023-188545
• Ghesquières H, et al. TIRHOL (BGB-A317-210): International Phase 2 Study in Relapsed/Refractory Classical Hodgkin Lymphoma. Presented at: Congrès de la Société Française d'Hématologie (SFH); March 2024; Paris, France.
• Ghesquières H, López-Guillermo A, De la Cruz F, et al. Final analysis from the LYSA phase 2 TIRHOL study (BGB-A317-210): tislelizumab in relapsed/refractory classical Hodgkin lymphoma. Presented at: 18th International Conference on Malignant Lymphoma (ICML); June 18-22, 2025; Lugano, Switzerland. https://doi.org/10.1002/hon.70093_130

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2020
• Primary Completion (Actual): December 12, 2022
• Study Completion (Actual): August 29, 2024

Study Registration Dates

• First Submitted: March 20, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (Actual): March 23, 2020

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 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; Antineoplastic Agents, Immunological; Antineoplastic Agents; tislelizumab
• Other Study ID Numbers: BGB-A317-210; 2019-002105-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.
• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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