HOUSTON – The according to a speaker at the Transplantation & Cellular Therapy Meetings.
In an ongoing phase 2 trial (NCT02841995), KD025 produced an overall response rate of 59%. Responses occurred in all affected organ systems, and 72% of responders experienced an improvement in Lee Symptom Scale (LSS) score.
The median duration of response was 28 weeks, but durability data are still maturing, according to Madan Jagasia, MBBS, of Vanderbilt University in Nashville, Tenn.
Dr. Jagasia and his colleagues evaluated KD025 in 54 adults who had persistent, active cGVHD after at least 2 months of steroid therapy. Sixty-seven percent of patients had received at least two prior lines of therapy, and 48% had involvement in four or more organs.
KD025 was given at three doses: 200 mg once daily (cohort 1), 200 mg twice daily (cohort 2), and 400 mg once daily (cohort 3). Patients also received glucocorticoid therapy, with or without calcineurin inhibitor therapy.
Cohort 1 included 17 patients who had a median age of 50 years (range, 20-63). They received KD025 for a median of 37 weeks, and six patients were still receiving KD025 at last follow-up.
Cohort 2 included 16 patients who had a median age of 55 years (range, 30-75). They received KD025 for a median of 33 weeks, and three patients were still receiving KD025 at last follow-up.
Cohort 3 included 21 patients who had a median age of 46 years (range, 25-75). They received KD025 for a median of 27 weeks, and 11 patients were still receiving KD025 at last follow-up.
The ORR was 59% (32/54) across the study, 65% (11/17) in cohort 1, 63% (10/16) in cohort 2, and 52% (11/21) in cohort 3. Three patients in cohort 3 didn’t reach the first response assessment, so the ORR in response-evaluable patients was 61% (11/18).
The ORR was 58% in patients who had received two or more prior lines of therapy, 55% in patients with severe cGVHD, and 62% in patients who had four or more organs involved.
“Responses were observed across all affected organ systems,” Dr. Jagasia said. “CRs [complete responses] were seen in all organs except the lung, and there were two partial responses observed in the lung.”
The median duration of response was 28 weeks. Eighty-two percent of responders in cohort 1, 50% of responders in cohort 2, and 36% of responders in cohort 3 had responses lasting 20 weeks or more.
“Keep in mind, the median duration of follow-up in cohort 3 is still short, and the durability data will continue to mature,” Dr. Jagasia said.
Most responders (72%) had at least a 7-point reduction in LSS score. Considering responders and nonresponders together, 65% of patients in cohort 1, 56% in cohort 2, and 52% in cohort 3 had an improvement in LSS score.
In all, 69% of patients stopped or reduced their use of steroids or other immunosuppressants. Seven patients completely discontinued steroids.
Forty-four percent of patients (n = 24) had a treatment-related adverse event (AE), but none of these AEs were considered serious. Four percent of patients (n = 2) had a related AE that led to treatment discontinuation, and 15% (n = 8) had grade 3/4 related AEs.
“The AEs were, overall, consistent with those expected in chronic graft-versus-host disease patients receiving corticosteroids,” Dr. Jagasia said. “Most important to note, there was no apparent increased risk of infection. Specifically, there was no CMV [cytomegalovirus] infection.”
The most common AEs were upper respiratory tract infection, fatigue, nausea, AST/ALT increase, and diarrhea. The most common grade 3/4 AEs were gamma-glutamyltransferase increase, hyperglycemia, anemia, and dyspnea.
There were three on-study deaths, all considered unrelated to KD025. One patient died of leukemia relapse, one died of lung infection, and one died of cardiac arrest.
Dr. Jagasia presented these results at the Transplantation & Cellular Therapy Meetings, held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: the American Society for Transplantation and Cellular Therapy (ASTCT).
Dr. Jagasia reported relationships with Kadmon Holdings, Mallinckrodt, and Janssen. The trial was sponsored by Kadmon Holdings.
SOURCE: Jagasia M et al. TCT 2019, Abstract 36.