Merck, known as MSD outside the United States and Canada, announced findings from the phase 2 KEYNOTE-170 trial investigating the use of Keytruda (pembrolizumab), the company’s anti-PD-1 therapy, in the cohort of patients with relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL), a type of non-Hodgkin lymphoma.
In the PMBCL cohort of KEYNOTE-170, Keytruda demonstrated an overall response rate (ORR) of 41 per cent (n=12/29), including a 24 per cent (n=7/29) complete response rate and a 17 percent (n=5/29) partial response rate, in patients who relapsed after or were refractory to autologous stem cell transplant (ASCT), or were ineligible for ASCT and failed two or more prior lines of therapy. These data were presented at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta on Sunday, December 10.
“There is a significant unmet need for patients with relapsed or refractory primary mediastinal large B-cell lymphoma,” said Pier Luigi Zinzani, M.D., Ph.D., associate professor of haematology, Institute of Hematology “L. e A. Seràgnoli,” University of Bologna. “These encouraging results represent another step in understanding the potential of Keytruda to help these patients who have already tried and progressed on prior therapies.”
Based on data from KEYNOTE-170 and the phase 1b KEYNOTE-013 trial, which is evaluating the safety, tolerability and efficacy of Keytruda monotherapy in patients with various blood cancers, the US Food and Drug Administration (FDA) has accepted for review a supplemental Biologics License Application (sBLA) for Keytruda (pembrolizumab) for the treatment of adult and paediatric patients with refractory primary mediastinal B-cell lymphoma, or who have relapsed after two or more prior lines of therapy. The FDA granted Priority Review status with a PDUFA, or target action, date of April 3, 2018. In January 2017, Keytruda was granted Breakthrough Therapy Designation by the FDA for this indication.
“These findings in patients with PMBCL are promising for a rare lymphoma that affects mainly young adults and has few effective treatment options in the relapsed or refractory treatment setting,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “If approved by the FDA, this would be our second blood cancer indication for Keytruda, following FDA approval for certain patients with classical Hodgkin Lymphoma earlier this year. The acceptance of our sBLA reinforces our ongoing commitment to finding new treatment advances in haematology.”
The Keytruda haematology programme includes more than 50 ongoing studies – including company sponsored, investigator sponsored and collaborative studies; several of these are registration-enabling trials.
KEYNOTE-170 is an ongoing, non-randomized, two-cohort, multicenter, phase 2 study evaluating the efficacy and safety of Keytruda (200 mg fixed dose every three weeks) in patients with relapsed or refractory PMBCL and in patients with relapsed or refractory Richter syndrome. The PMBCL cohort enrolled patients who relapsed after or were refractory to ASCT, or were ineligible for ASCT; patients ineligible for ASCT had to have relapsed or refractory disease after two or more lines of prior therapy. The primary endpoint was ORR by blinded independent central review; key secondary endpoints included duration of response and safety and tolerability.
In the efficacy population (n=29), ORR was 41 per cent (n=12) (95% CI, 24-61), with a complete response rate of 24 per cent (n=7) (95% CI,10-44) and a partial response rate of 17 per cent (n=5) (95% CI, 6-36). Median duration of follow-up was 10.5 months (range: 0.1-17.7). Median time to response was 2.8 months (range: 2.4-5.5). Median duration of response was not reached (range: 1.1+ to 13.6+ months).
Treatment-related adverse events (TRAEs) were consistent with previously reported safety data for Keytruda. Of the 53 patients evaluated for safety, 57 per cent (n=30) experienced TRAEs, including 21 per cent (n=11) who experienced Grade 3-4 TRAEs. The most common TRAEs (greater than or equal to 5%) were neutropenia (n=11), hypothyroidism (n=4), asthenia (n=3) and pyrexia (n=3). Immune-mediated adverse events of all grades occurred in 11 percent (n=6) of patients; these include hypothyroidism (n=4), hyperthyroidism (n=2), pneumonitis (n=1) and thyroiditis (n=1). There were no treatment-related deaths.
PMBCL is a sub-type of diffuse large B-cell lymphoma (a type of non-Hodgkin lymphoma) that starts in the space between the lungs, called the mediastinum. PMBCL mainly affects young adults (with a median age of 35), and occurs slightly more often in women. PMBCL accounts for two to four percent of all non-Hodgkin lymphomas in the US.
Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that 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.