Classical Hodgkin Lymphoma
Conditions
Brief summary
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.
Interventions
DRUGTislelizumab
200 milligrams (mg) intravenously every 3 weeks (Q3W)
Sponsors
Lymphoma Study Association
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) | 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. | 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. |
| Duration of Response (DOR) | 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. | 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. |
| Time to Response (TTR) | 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. | 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. |
| Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the date of the first dose of tislelizumab through 90 days after the last dose (maximum duration of tislelizumab exposure was 168 weeks) | 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. |
Countries
Australia, United States
Participant flow
Recruitment details
This study was conducted at multiple centers across France, the United States, Belgium, and Australia from August 20, 2020, to August 29, 2024.
Pre-assignment details
After enrollment, open-label tislelizumab treatment began. Screening was completed within 28 days before the first dose. Treatment started within 14 days of eligibility confirmation, within the screening window. Treatment continued until disease progression, unacceptable toxicity, or withdrawal. Participants who did not meet eligibility criteria during screening were excluded prior to assignment to treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 14 |
| 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. | 31 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 9 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Study closed by sponsor | 10 | 22 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 43.9 Years STANDARD_DEVIATION 15.78 | 59.6 Years STANDARD_DEVIATION 21.95 | 54.7 Years STANDARD_DEVIATION 21.37 |
| Number of prior lines of therapy for cHL 1 | 0 Participants | 7 Participants | 7 Participants |
| Number of prior lines of therapy for cHL 2 | 9 Participants | 17 Participants | 26 Participants |
| Number of prior lines of therapy for cHL 3 | 4 Participants | 6 Participants | 10 Participants |
| Number of prior lines of therapy for cHL 4 | 1 Participants | 1 Participants | 2 Participants |
| Patient Status at Time of Enrollment Refractory | 0 Participants | 13 Participants | 13 Participants |
| Patient Status at Time of Enrollment Relapse/Progression | 14 Participants | 18 Participants | 32 Participants |
| Race/Ethnicity, Customized Not Reported | 11 Participants | 26 Participants | 37 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 20 Participants | 30 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Normal activities) | 10 Participants | 18 Participants | 28 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Ambulatory able to carry out work) | 4 Participants | 13 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 14 | 9 / 31 |
| other Total, other adverse events | 12 / 14 | 30 / 31 |
| serious Total, serious adverse events | 4 / 14 | 9 / 31 |
Outcome results
Primary
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.
Time frame: 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.
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Overall Response Rate (ORR) | 64.3 Percentage of Participants |
| Cohort 2 | Overall Response Rate (ORR) | 64.5 Percentage of Participants |
| Total | Overall Response Rate (ORR) | 64.4 Percentage of Participants |
Comparison: The primary analysis was conducted on both cohorts combined, A binomial exact test was performed to test the null hypothesis (H0: ORR = 45% based on previous clinical trials) and alternative hypothesis (ORR \>45%). If the one-sided p-value was ≤ 0.05, tislelizumab was considered to statistically significantly increase ORR compared to the historical control.p-value: 0.0044Binomial Exact Test
Secondary
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.
Time frame: 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.
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Complete Response Rate (CRR) | 42.9 Percentage of Participants |
| Cohort 2 | Complete Response Rate (CRR) | 25.8 Percentage of Participants |
| Total | Complete Response Rate (CRR) | 31.1 Percentage of Participants |
Secondary
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.
Time frame: 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.
Population: The responder analysis set only included participants with a confirmed response (CR) or partial response (PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Duration of Response (DOR) | 12.25 months |
| Cohort 2 | Duration of Response (DOR) | 6.64 months |
| Total | Duration of Response (DOR) | 12.25 months |
Secondary
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.
Time frame: From the date of the first dose of tislelizumab through 90 days after the last dose (maximum duration of tislelizumab exposure was 168 weeks)
Population: Safety Analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with any TEAEs | 12 Participants |
| Cohort 1 | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with any TEAEs with grade >= 3 | 4 Participants |
| Cohort 1 | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with any SAEs | 4 Participants |
| Cohort 2 | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with any TEAEs | 30 Participants |
| Cohort 2 | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with any TEAEs with grade >= 3 | 12 Participants |
| Cohort 2 | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of participants with any SAEs | 9 Participants |
Secondary
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.
Time frame: 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.
Population: Safety Analysis Set. Only participants who had achieved an overall response were included in the analysis of time to response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Time to Response (TTR) | 2.69 months |
| Cohort 2 | Time to Response (TTR) | 2.69 months |
| Total | Time to Response (TTR) | 2.69 months |