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Heavily pre-treated patients with relapsed or refractory classical Hodgkin lymphoma: Pembrolizumab, as a monotherapy, shows overall response rates of 73 to 83%, with complete response rates of 27 to 30%


The findings from KEYNOTE-087, the phase 2 study investigating the use of Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, as a monotherapy in patients with relapsed or refractory classical Hodgkin lymphoma ( cHL ) were announced.

Results included an analysis of outcome measurements from the study’s three patient cohorts: patients whose disease progressed following an autologous stem cell transplantation and subsequent treatment with Brentuximab vedotin ( Adcetris ), an antibody drug conjugate ( Cohort 1 ); patients who failed salvage chemotherapy and were ineligible for a transplant and whose disease progressed following treatment with Brentuximab vedotin ( Cohort 2 ); and patients whose disease progressed after transplant and who did not receive Brentuximab vedotin after transplant ( Cohort 3 ).
Data showed that the overall response rate ( ORR ) was more than 70% across all three cohorts with the highest ORR, at 83%, observed in Cohort 2.
Results also included an analysis of patients with primary refractory disease, defined as failure to achieve complete or partial response to first-line treatment.
In this patient population, the ORR ( by investigator review ) was 78%. Additionally, 90 to 93% of patients experienced a reduction in tumor size across all three cohorts.

Data from KEYNOTE-087 supported the recent Breakthrough Therapy Designation granted to Pembrolizumab by the U.S. Food and Drug Administration ( FDA ) for this type of blood cancer.
Additionally, findings from this study support the continued development of Pembrolizumab in patients with cHL, including a phase 3 registration-enabling study ( KEYNOTE-204 ) designed to evaluate monotherapy Pembrolizumab versus Brentuximab vedotin in patients with relapsed or refractory cHL.

Results presented at ASCO were based on an analysis of 90 patients across three study cohorts. These data showed ( per investigator review ):

In Cohort 1 ( progressed after transplant and subsequent Brentuximab vedotin treatment; n=30 ), ORR was 73% ( 95% CI, 54-88 ), with complete responses in 27% ( 95% CI, 12-46 ) and partial responses in 47% ( 95% CI, 28-66 ) of patients. Seventeen percent of patients had stable disease ( 95% CI, 6-35 ) and 10% of patients had progressive disease ( 95% CI, 2-27 ).

In Cohort 2 ( progressed following salvage chemotherapy, transplant-ineligible, and progressed following Brentuximab vedotin treatment; n=30 ), ORR was 83% ( 95% CI, 65-94 ), with complete responses in 30% ( 95% CI, 15-49 ) and partial responses in 53% ( 95% CI, 34-72 ) of patients. Seven percent of patients had stable disease ( 95% CI, 1-22 ) and 7% of patients had progressive disease ( 95% CI, 1-22 ).

In Cohort 3 ( progressed after transplant and not treated with Brentuximab vedotin after transplant; n=30 ), ORR was 73% ( 95% CI, 54-88 ), with complete responses in 30% ( 95% CI, 15-49 ) and partial responses in 43% of patients ( 95% CI, 26-63 ). Thirteen percent of patients had stable disease ( 95% CI, 4-31 ) and 13% of patients had progressive disease ( 95% CI, 4-31 ).

In patients with primary refractory disease ( n=37 ), ORR was 78% ( 95% CI, 62-90 ), with complete responses in 35% ( 95% CI, 20-53 ) and partial responses in 43% ( 95% CI, 27-61 ) of patients. Eleven percent of patients had stable disease ( 95% CI, 3-25 ) and 8% of patients had progressive disease ( 95% CI, 2-22 ).

The safety profile of Pembrolizumab was consistent with that observed in previously reported studies. Grade 3-4 treatment-related adverse events were observed in 4% of patients and included neutropenia ( n=1 ), increased amylase ( n=1 ), cytokine release syndrome ( n=1 ), herpes zoster ( n=1 ), increased lipase ( n=1 ), lichenoid dermatosis ( n=1 ), colitis ( n=1 ), and diarrhea ( n=1 ).
Two patients discontinued due to treatment-related adverse events ( grade 2 infusion-related reaction and grade 2 pneumonitis; both Cohort 2 ).
The immune-mediated adverse events ( any grade ) were rash ( n=4, all grade 1 ), pneumonitis ( n=2, both grade 2 ), and colitis ( n=1, grade 3 ).

There were no treatment-related deaths.

KEYNOTE-087 is a multicenter, open-label, multi-cohort, activity-estimating phase 2 trial evaluating Pembrolizumab ( 200 mg fixed dose every three weeks ) monotherapy in patients with relapsed or refractory cHL across three cohorts.
The primary endpoints include overall safety, tolerability, and ORR ( per central review ); secondary endpoints include ORR ( per investigator review ), progression-free survival ( PFS ), and overall survival ( OS ).
The patient cohorts are intended to assess the outcome measures in patients whose disease progressed following an autologous stem cell transplantation and subsequent treatment with Brentuximab vedotin, an antibody drug conjugate ( Cohort 1 ); patients who failed salvage chemotherapy and were ineligible for a transplant and whose disease progressed following treatment with Brentuximab vedotin ( Cohort 2 ); and patients whose disease progressed after transplant and who did not receive Brentuximab vedotin after transplant ( Cohort 3 ).

Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. ( Xagena )

Source: Merck, 2016

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