MULTICOHORT PHASE 2 STUDY OF PEMBROLIZUMAB FOR RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA (R/R CHL): KEYNOTE-087
(Abstract release date: 05/19/16)
EHA Library. Chen R. 06/12/16; 135288; S794
Robert Chen
Contributions
Contributions
Abstract
Abstract: S794
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:15 - 08:30
Location: Hall A2
Background
Patients with cHL who relapse after autologous stem cell transplantation (ASCT) or progress after brentuximab vedotin (BV) have a poor prognosis. In cHL, nearly universal 9p24.1 amplification, as well as less likely mechanisms such as Epstein-Barr virus infection and chromosomal rearrangements, induce PD-L1 and PD-L2 expression on the tumor cell surface, suggesting that cHL may have a genetically determined dependence on the PD-1 pathway. Pembrolizumab is a humanized monoclonal antibody against PD-1 that blocks interaction with PD-L1 and PD-L2. In the phase 1b KEYNOTE-013 study, pembrolizumab demonstrated high antitumor activity (objective response rate [ORR] of 65%) in heavily pretreated patients with cHL. KEYNOTE-087 is a phase 2 study designed to further evaluate the clinical activity of pembrolizumab in this patient population.
Aims
To determine the ORR, safety, and tolerability of pembrolizumab in patients with R/R cHL.
Methods
KEYNOTE-087 (NCT02453594) is a multicenter, single-arm, multicohort phase 2 study designed to evaluate the clinical activity of pembrolizumab in 3 cohorts: R/R cHL after ASCT and subsequent BV therapy (cohort 1); ineligible for ASCT due to chemo-resistance (no response to salvage chemotherapy) and BV therapy failure (cohort 2); and R/R cHL after ASCT but not treated with BV after ASCT (cohort 3). Patients received pembrolizumab at a fixed dose of 200 mg intravenously every 3 weeks. Primary end point was ORR, with response assessed every 12 weeks according to Revised Response Criteria for Malignant Lymphomas. A prespecified interim analysis, based on investigator-assessed response, was performed after 30 patients in cohorts 1 and 2 reached the first response assessment. Informed consent was obtained for all patients.
Results
At the time of data cutoff (Feb 1, 2016), 60 patients were evaluable for cohorts 1 and 2. Median (range) age was 36 (19 - 64) years in cohort 1 and 33 (20 - 71) in cohort 2. 35% had primary refractory disease (no response to frontline therapy), 67% received ≥4 prior lines of therapy, and by design 100% failed prior BV. ORR among 30 patients in cohort 1 was 70% (95% CI, 51% - 85%). 6 patients (20%) achieved complete response (CR; residual mass permitted if PET negative), 15 (50%) partial response (PR), and 6 (20%) stable disease as best response. ORR among 30 patients in cohort 2 was 80% (95% CI, 61% - 92%). 8 patients (27%) achieved CR, 16 (53%) PR, and 4 (13%) stable disease as best response. With a median of 6 treatment cycles, the most common treatment-related AEs (TRAEs) were pyrexia (13%), diarrhea (8%), and fatigue, platelet count decrease, dry skin, and cough (7% each). There were 7 grade 3 TRAEs in 3 patients: neutropenia, colitis, diarrhea, cytokine release syndrome, herpes zoster infection, increased amylase, and lichen planus; and only 1 grade 4 TRAE, increased lipase. There were no treatment-related deaths.
Conclusion
PD-1 blockade with pembrolizumab shows frequent responses in heavily pretreated patients with cHL. Of note, pembrolizumab provided a high ORR (80%) in patients who were not candidates for ASCT and failed previous BV therapy. Cohort 3 continues accrual and interim analysis results will be presented.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Keyword(s): Hodgkin's lymphoma
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:15 - 08:30
Location: Hall A2
Background
Patients with cHL who relapse after autologous stem cell transplantation (ASCT) or progress after brentuximab vedotin (BV) have a poor prognosis. In cHL, nearly universal 9p24.1 amplification, as well as less likely mechanisms such as Epstein-Barr virus infection and chromosomal rearrangements, induce PD-L1 and PD-L2 expression on the tumor cell surface, suggesting that cHL may have a genetically determined dependence on the PD-1 pathway. Pembrolizumab is a humanized monoclonal antibody against PD-1 that blocks interaction with PD-L1 and PD-L2. In the phase 1b KEYNOTE-013 study, pembrolizumab demonstrated high antitumor activity (objective response rate [ORR] of 65%) in heavily pretreated patients with cHL. KEYNOTE-087 is a phase 2 study designed to further evaluate the clinical activity of pembrolizumab in this patient population.
Aims
To determine the ORR, safety, and tolerability of pembrolizumab in patients with R/R cHL.
Methods
KEYNOTE-087 (NCT02453594) is a multicenter, single-arm, multicohort phase 2 study designed to evaluate the clinical activity of pembrolizumab in 3 cohorts: R/R cHL after ASCT and subsequent BV therapy (cohort 1); ineligible for ASCT due to chemo-resistance (no response to salvage chemotherapy) and BV therapy failure (cohort 2); and R/R cHL after ASCT but not treated with BV after ASCT (cohort 3). Patients received pembrolizumab at a fixed dose of 200 mg intravenously every 3 weeks. Primary end point was ORR, with response assessed every 12 weeks according to Revised Response Criteria for Malignant Lymphomas. A prespecified interim analysis, based on investigator-assessed response, was performed after 30 patients in cohorts 1 and 2 reached the first response assessment. Informed consent was obtained for all patients.
Results
At the time of data cutoff (Feb 1, 2016), 60 patients were evaluable for cohorts 1 and 2. Median (range) age was 36 (19 - 64) years in cohort 1 and 33 (20 - 71) in cohort 2. 35% had primary refractory disease (no response to frontline therapy), 67% received ≥4 prior lines of therapy, and by design 100% failed prior BV. ORR among 30 patients in cohort 1 was 70% (95% CI, 51% - 85%). 6 patients (20%) achieved complete response (CR; residual mass permitted if PET negative), 15 (50%) partial response (PR), and 6 (20%) stable disease as best response. ORR among 30 patients in cohort 2 was 80% (95% CI, 61% - 92%). 8 patients (27%) achieved CR, 16 (53%) PR, and 4 (13%) stable disease as best response. With a median of 6 treatment cycles, the most common treatment-related AEs (TRAEs) were pyrexia (13%), diarrhea (8%), and fatigue, platelet count decrease, dry skin, and cough (7% each). There were 7 grade 3 TRAEs in 3 patients: neutropenia, colitis, diarrhea, cytokine release syndrome, herpes zoster infection, increased amylase, and lichen planus; and only 1 grade 4 TRAE, increased lipase. There were no treatment-related deaths.
Conclusion
PD-1 blockade with pembrolizumab shows frequent responses in heavily pretreated patients with cHL. Of note, pembrolizumab provided a high ORR (80%) in patients who were not candidates for ASCT and failed previous BV therapy. Cohort 3 continues accrual and interim analysis results will be presented.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Keyword(s): Hodgkin's lymphoma
Abstract: S794
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:15 - 08:30
Location: Hall A2
Background
Patients with cHL who relapse after autologous stem cell transplantation (ASCT) or progress after brentuximab vedotin (BV) have a poor prognosis. In cHL, nearly universal 9p24.1 amplification, as well as less likely mechanisms such as Epstein-Barr virus infection and chromosomal rearrangements, induce PD-L1 and PD-L2 expression on the tumor cell surface, suggesting that cHL may have a genetically determined dependence on the PD-1 pathway. Pembrolizumab is a humanized monoclonal antibody against PD-1 that blocks interaction with PD-L1 and PD-L2. In the phase 1b KEYNOTE-013 study, pembrolizumab demonstrated high antitumor activity (objective response rate [ORR] of 65%) in heavily pretreated patients with cHL. KEYNOTE-087 is a phase 2 study designed to further evaluate the clinical activity of pembrolizumab in this patient population.
Aims
To determine the ORR, safety, and tolerability of pembrolizumab in patients with R/R cHL.
Methods
KEYNOTE-087 (NCT02453594) is a multicenter, single-arm, multicohort phase 2 study designed to evaluate the clinical activity of pembrolizumab in 3 cohorts: R/R cHL after ASCT and subsequent BV therapy (cohort 1); ineligible for ASCT due to chemo-resistance (no response to salvage chemotherapy) and BV therapy failure (cohort 2); and R/R cHL after ASCT but not treated with BV after ASCT (cohort 3). Patients received pembrolizumab at a fixed dose of 200 mg intravenously every 3 weeks. Primary end point was ORR, with response assessed every 12 weeks according to Revised Response Criteria for Malignant Lymphomas. A prespecified interim analysis, based on investigator-assessed response, was performed after 30 patients in cohorts 1 and 2 reached the first response assessment. Informed consent was obtained for all patients.
Results
At the time of data cutoff (Feb 1, 2016), 60 patients were evaluable for cohorts 1 and 2. Median (range) age was 36 (19 - 64) years in cohort 1 and 33 (20 - 71) in cohort 2. 35% had primary refractory disease (no response to frontline therapy), 67% received ≥4 prior lines of therapy, and by design 100% failed prior BV. ORR among 30 patients in cohort 1 was 70% (95% CI, 51% - 85%). 6 patients (20%) achieved complete response (CR; residual mass permitted if PET negative), 15 (50%) partial response (PR), and 6 (20%) stable disease as best response. ORR among 30 patients in cohort 2 was 80% (95% CI, 61% - 92%). 8 patients (27%) achieved CR, 16 (53%) PR, and 4 (13%) stable disease as best response. With a median of 6 treatment cycles, the most common treatment-related AEs (TRAEs) were pyrexia (13%), diarrhea (8%), and fatigue, platelet count decrease, dry skin, and cough (7% each). There were 7 grade 3 TRAEs in 3 patients: neutropenia, colitis, diarrhea, cytokine release syndrome, herpes zoster infection, increased amylase, and lichen planus; and only 1 grade 4 TRAE, increased lipase. There were no treatment-related deaths.
Conclusion
PD-1 blockade with pembrolizumab shows frequent responses in heavily pretreated patients with cHL. Of note, pembrolizumab provided a high ORR (80%) in patients who were not candidates for ASCT and failed previous BV therapy. Cohort 3 continues accrual and interim analysis results will be presented.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Keyword(s): Hodgkin's lymphoma
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:15 - 08:30
Location: Hall A2
Background
Patients with cHL who relapse after autologous stem cell transplantation (ASCT) or progress after brentuximab vedotin (BV) have a poor prognosis. In cHL, nearly universal 9p24.1 amplification, as well as less likely mechanisms such as Epstein-Barr virus infection and chromosomal rearrangements, induce PD-L1 and PD-L2 expression on the tumor cell surface, suggesting that cHL may have a genetically determined dependence on the PD-1 pathway. Pembrolizumab is a humanized monoclonal antibody against PD-1 that blocks interaction with PD-L1 and PD-L2. In the phase 1b KEYNOTE-013 study, pembrolizumab demonstrated high antitumor activity (objective response rate [ORR] of 65%) in heavily pretreated patients with cHL. KEYNOTE-087 is a phase 2 study designed to further evaluate the clinical activity of pembrolizumab in this patient population.
Aims
To determine the ORR, safety, and tolerability of pembrolizumab in patients with R/R cHL.
Methods
KEYNOTE-087 (NCT02453594) is a multicenter, single-arm, multicohort phase 2 study designed to evaluate the clinical activity of pembrolizumab in 3 cohorts: R/R cHL after ASCT and subsequent BV therapy (cohort 1); ineligible for ASCT due to chemo-resistance (no response to salvage chemotherapy) and BV therapy failure (cohort 2); and R/R cHL after ASCT but not treated with BV after ASCT (cohort 3). Patients received pembrolizumab at a fixed dose of 200 mg intravenously every 3 weeks. Primary end point was ORR, with response assessed every 12 weeks according to Revised Response Criteria for Malignant Lymphomas. A prespecified interim analysis, based on investigator-assessed response, was performed after 30 patients in cohorts 1 and 2 reached the first response assessment. Informed consent was obtained for all patients.
Results
At the time of data cutoff (Feb 1, 2016), 60 patients were evaluable for cohorts 1 and 2. Median (range) age was 36 (19 - 64) years in cohort 1 and 33 (20 - 71) in cohort 2. 35% had primary refractory disease (no response to frontline therapy), 67% received ≥4 prior lines of therapy, and by design 100% failed prior BV. ORR among 30 patients in cohort 1 was 70% (95% CI, 51% - 85%). 6 patients (20%) achieved complete response (CR; residual mass permitted if PET negative), 15 (50%) partial response (PR), and 6 (20%) stable disease as best response. ORR among 30 patients in cohort 2 was 80% (95% CI, 61% - 92%). 8 patients (27%) achieved CR, 16 (53%) PR, and 4 (13%) stable disease as best response. With a median of 6 treatment cycles, the most common treatment-related AEs (TRAEs) were pyrexia (13%), diarrhea (8%), and fatigue, platelet count decrease, dry skin, and cough (7% each). There were 7 grade 3 TRAEs in 3 patients: neutropenia, colitis, diarrhea, cytokine release syndrome, herpes zoster infection, increased amylase, and lichen planus; and only 1 grade 4 TRAE, increased lipase. There were no treatment-related deaths.
Conclusion
PD-1 blockade with pembrolizumab shows frequent responses in heavily pretreated patients with cHL. Of note, pembrolizumab provided a high ORR (80%) in patients who were not candidates for ASCT and failed previous BV therapy. Cohort 3 continues accrual and interim analysis results will be presented.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Keyword(s): Hodgkin's lymphoma
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