Valemetostat Yields Enduring Responses in Relapsed/Refractory PTCL

"This phase 2 trial showed a favorable risk/benefit profile of valemetostat monotherapy in patients with relapsed or refractory [PTCL], with high and durable responses observed," according to the study authors.

Treatment with valemetostat (Ezharmia) demonstrated enduring responses with a manageable safety profile among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL), according to findings from the phase 2 VALENTINE-PTCL01 trial (NCT04703192) published in Lancet Oncology.

Based on blinded independent central review (BICR), valemetostat yielded an objective response in 44% (n = 52/119; 95% CI, 35%-53%) of patients, which included complete responses (CRs) in 14% (n = 17/119) and partial responses (PRs) in 29% (n = 35/119). Additionally, the median time to first response was 8.1 weeks (IQR, 7.8-8.3), and the median duration of response (DOR) was 11.9 months (95% CI, 7.8-not evaluable [NE]). Data also showed a median duration of CR of 11.2 months (95% CI, 4.2-NE).

Study treatment produced a median progression-free survival (PFS) of 5.5 months (95% CI, 3.5-8.3) among all patients. Among those with a CR and a PR, respectively, the median PFS was 16.6 months (95% CI, 9.7-NE) and 11.3 months (95% CI, 6.1-NE). The estimated median overall survival (OS) was 17.0 months (95% CI, 13.5-NE).

“This phase 2 trial showed a favorable risk/benefit profile of valemetostat monotherapy in patients with relapsed or refractory [PTCL], with high and durable responses observed. Valemetostat also demonstrated an acceptable safety profile with mostly manageable treatment-emergent adverse events [TEAEs] in patients with relapsed or refractory [PTCL] and adult T-cell leukemia [or] lymphoma,” Pier Luigi Zinzani MD, PhD, of the Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, in Bologna, Italy, and coauthor wrote in the publication. “Treatment options are scarce for patients with relapsed or refractory T-cell lymphomas, and thus a great need exists for additional effective therapies.”

In the open-label, multicenter, single-arm phase 2 VALENTINE-PTCL01 trial, 133 patients with relapsed/refractory PTCL and 22 patients with relapsed/refractory adult T-cell leukemia or lymphoma were assigned to receive valemetostat at 200 mg orally daily in continuous 28-day cycles until progressive disease or unacceptable toxicity.

The trial’s primary end point in the PTCL population was ORR based on BICR evaluation. Secondary end points for this group included CR rate, PR rate, DOR, duration of CR, PFS, and OS.

Patients 18 years and older with a locally confirmed diagnosis of PTCL based on 2016 World Health Organization criteria or adult T-cell leukemia or lymphoma per Lymphoma Study Group diagnostic guidelines were eligible for enrollment on the trial. Other requirements for study entry included having an estimated life expectancy of more than 3 months, an ECOG performance status of 0 to 2, relapsed/refractory disease following at least 1 prior line of systemic therapy, and at least 1 measurable lesion.

The median age was 69.0 years (IQR, 58.0-74.0) in the PTCL cohort and 66.5 years (IQR, 54.0-73.0) in the adult T-cell leukemia or lymphoma cohort. In each respective population, most patients were male (68% vs 68%) and had an ECOG performance status of 1 (49% vs 59%). A higher proportion of patients were White in the PTCL population (60%), and most were Black or African American in the adult T-cell leukemia or lymphoma cohort (45%).

TEAEs affected 96% (n = 128/133) of patients with PTCL and 100% (n = 22/22) of those in the adult T-cell leukemia or lymphoma group. Additionally, grade 3 or higher TEAEs occurred in 58% (n = 77/133) and 86% (n = 19/22) of patients, respectively, with the most common types in each group including thrombocytopenia (23% vs 50%), anemia (19% vs 46%), and neutropenia (17% vs 18%).

Serious TEAEs occurred in 40% (n = 53/133) of patients with PTCL and 68% (n = 15/22) of those with adult T-cell lymphoma or leukemia. In each respective cohort, data showed TEAEs leading to treatment interruption (50% vs 68%), dose reductions (16% vs 5%), and treatment discontinuation (10% vs 9%). Additionally, 39% (n = 52/133) and 73% (n = 16/22) of patients in each group died before the data cutoff; investigators considered all deaths as unrelated to treatment with valemetostat.

Reference

Zinzani PL, Izutsu K, Mehta-Shah N, et al. Valemetostat for patients with relapsed or refractor peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. Published online October 29, 2024. doi:10.1016/S1470-2045(24)00503-5