FDA Grants Priority Review Pembrolizumab for Relapsed/Refractory Classical Hodgkin Lymphoma

The FDA has granted Priority Review to a supplemental Biologics License Application (sBLA) for pembrolizumab (Keytruda) as treatment of patients with relapsed or refractory classic Hodgkin lymphoma (cHL). The FDA has set a target action date of October 30, 2020.¹

The sBLA was granted this designation based on data from the pivotal phase 3 KEYNOTE-204 clinical trial, in which the checkpoint inhibitor significantly improved the progression-free survival (PFS) compared with the current standard of care, brentuximab vedotin (Adcetris).

“cHL accounts for more than 9 in 10 cases of Hodgkin lymphoma, which impacts approximately 7400 patients a year in the United States. For patients with cHL who do not achieve remission after first-line treatment, there is a particularly poor prognosis due to the limited options available,” said Jonathan Cheng, MD, vice president, Oncology Clinical Research, Merck Research Laboratories, in a statement. “We look forward to working with the FDA to bring KEYTRUDA to more patients with cHL after initial treatment.”

Pembrolizumab induced a 4.9-month PFS benefit over the standard of care as treatment of patients with relapsed/refractory cHL in the KEYNOTE-204 study, according to data presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program. The median PFS with pembrolizumab was 13.2 months versus 8.3 months with brentuximab vedotin (HR, 0.65; 95% CI, 0.48-0.88; P =.00271).²

PFS also favored pembrolizumab over brentuximab vedotin in several subgroups, which included patients ineligible for autologous stem cell transplant (HR, 0.61; 95% CI, 0.42-1.23), patients with primary disease (HR, 0.52; 95% CI, 0.33-0.83), and patients who had not received prior brentuximab vedotin (HR, 0.67; 95% CI, 0.49-0.92).

The overall response rate for pembrolizumab was 65.6% versus 54.2% for the control arm. In the pembrolizumab arm, 24.5% of patients achieved a complete response and 41.1% achieved a partial response. The duration of response with pembrolizumab was 20.7 months versus 13.8 months, showing a 6.9-month increase over the standard of care.

The safety profiles observed in this study were consistent with the known profiles of each agent. Serious treatment-related adverse events (TRAEs) were observed more frequently in patients receiving the checkpoint inhibitor, where 16.2% (n = 24) of patients reported a serious TRAE. The most common TRAEs included hypothyroidism (15.5%), pyrexia (12.8%), pruritis (10.8%), and fatigue (8.8%).

A total of 19 patients (12.8%) in the pembrolizumab arm discontinued treatment due to TRAEs compared with 25 (16.4%) in the brentuximab vedotin arm. There was 1 death due to a TRAE with pembrolizumab, which was a case of grade 5 pneumonia.

Immune-mediated adverse events (IRAEs) were also higher in the pembrolizumab arm, with the most common IRAEs being hypothyroidism (18.9%) and pneumonitis (10.8%). Only 5.4% of cases of pneumonitis were grade 3/4. Of the 16 patients who reported pneumonitis, 15 patients required treatment with corticosteroids, which led to resolution in 12 patients.

Overall, 304 patients were enrolled in the randomized, open-label KEYNOTE-204 clinical trial (NCT02684292). A total of 151 patients were assigned to the pembrolizumab group and 153 to the control group. Patients had to be at least 18 years of age to participate in the clinical trial, and they had to be either post autologous stem cell transplant or ineligible for transplant. Patients who had not received prior brentuximab vedotin as well as those who had been exposed to this agent were included in the study.

KEYNOTE-204 also served as the confirmatory trial for the accelerated approval of pembrolizumab in hematologic indications. Merck continues to evaluate pembrolizumab in other hematologic malignancies through a broad clinical program, which includes 3 registrational studies in cHL and primary mediastinal large B-cell lymphoma, with over 60 investigator-initiated trials across 15 tumor types.¹

_References

_{1. FDA Grants Priority Review to Merck’s Supplemental Biologics License Application for KEYTRUDA® (pembrolizumab) for Second-Line Treatment of Patients With Relapsed or Refractory Classical Hodgkin Lymphoma. Merck. July 9, 2020. Accessed July 9, 2020. https://bit.ly/3iLDfNX}

_{2. Kuruvilla J, Ramchandren R, Santoro A, et al. KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). Presented at: 2020 American Society of Clinical Oncology Virtual Scientific Program; May 29, 2020. Abstract 8005}