Open-Label, Phase 1b/2, Dose-Escalation Study of a Novel Agent in Patients with RRMM (STOMP)

Conference Correspondent —December 16, 2020

In the phase 3 BOSTON study, the combination of selinexor (SEL), a novel, first-in-class oral selective inhibitor of nuclear export, dexamethasone, and bortezomib, significantly increased progression-free survival (PFS) and overall response rate (ORR) with significantly reduced peripheral neuropathy compared with standard twice-weekly bortezomib and dexamethasone (Pd) in heavily pretreated patients with multiple myeloma. This open-label, phase 1b/2 dose-escalation study tested the combination of Pd with the addition of SEL (SPd) to ascertain if the SPd combination improved efficacy and had acceptable tolerability compared with Pd.

STOMP is a multicenter, open-label, phase 1b/2, dose-escalation study. Patients with relapsed/ refractory multiple myeloma (RRMM) who received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor (in separate or the same regimens), were eligible for enrollment. As of June 1, 2020, 52 patients (28 male and 24 female) were enrolled. The median age was 64 years (range, 43-85 years). Patients received a median of 3 (range, 1-10) prior therapies, including 44 (84.6%) with autologous stem-cell transplantation. Oral SEL was evaluated in 2 different dosing schedules in 28-day cycles: once weekly 60, 80, or 100 mg or twice weekly 60 or 80 mg, with escalating doses of pomalidomide 2, 3, or 4 mg (days 1-21), and dexamethasone 20 mg twice weekly or 40 mg once weekly. The primary objectives of the study were to determine the maximum tolerated dose, the recommended phase 2 dose (RP2D), and to assess the safety, tolerability, ORR, and PFS of the combination of SPd in patients with RRMM.

Of the original 52 enrolled patients, 47 were evaluable for response. Previously treated/refractory rates were as follows: lenalidomide (100%, 96%), bortezomib (94%, 45%), carfilzomib (38%, 34%), pomalidomide (30%, 30%), daratumumab (21%, 21%). Among pomalidomide-naïve patients (N = 33), all patients (100%) received prior lenalidomide and 31 patients (94%) had multiple myeloma lenalidomide-refractory disease.

Among the 33 patients who were pomalidomide-naive, the ORR was 58% (1 complete response, 5 very good partial responses, and 13 partial responses) and the median PFS and overall survival (OS) were 12.3 months and 19.0 months, respectively. For the 14 patients who received pomalidomide previously, the ORR was 36% (1 very good partial response and 4 partial responses), and the median PFS and OS were 8.8 months and 8.0 months, respectively.

During the escalation phase, 8 dose-limiting toxicities were observed. Common hematologic treatment-related adverse events (TRAEs) included (all grades, grades ≥3) neutropenia (62%, 56%), anemia (60%, 37%), and thrombocytopenia (56%, 35%). Common nonhematologic TRAEs included nausea (62%, 2%), fatigue (56%, 12%), decreased appetite (48%, 2%), weight loss (42%, 0%), diarrhea (35%, 0%), and vomiting (23%, 2%). Rates of grade ≥3 hematologic TRAEs were lower in the once-weekly versus twice-weekly schedules of SEL: thrombocytopenia (29% vs 44%) and anemia (32% vs 44%). Based on all of the safety data, the RP2D was SEL 60 mg once weekly, pomalidomide 4 mg (days 1-21), and dexamethasone 40 mg once weekly.

The all-oral SPd combination appears to confer relatively high ORR with good durability and promising PFS in patients with heavily pretreated multiple myeloma compared with patients treated with Pd. There were no unexpected TRAEs. All TRAEs were manageable with appropriate supportive care and/or dose modifications.


Reference

Abstract 726. ASH 2020. December 7, 2020. Selinexor in combination with pomalidomide and dexamethasone (SPd) for treatment of patients with relapsed refractory multiple myeloma (RRMM).

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Last modified: December 16, 2020

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