Background：

Patients (pts) with relapsed/refractory (R/R) DLBCL and iNHL who are ineligible for, or relapse after, high-dose chemotherapy (HDC)/autologous stem cell transplantation (ASCT) have a poor prognosis and limited treatment options. Selinexor, a selective inhibitor of nuclear export has received accelerated approval by the U.S. Food and Drug Administration, for the treatment of adult patients with R/R DLBCL. Phase I/II study (NCT05265975), selinexor in combination with lenalidomide and rituximab (R2) for R/R DLBCL and iNHL, is ongoing. Phase I results were previously reported at ICML 2023 (Weili Zhao et al., ICML 2023, #658) and the recommended phase 2 dosing (RP2D) was determined.

Aims:

Here we update the preliminary results of SWATCH study.

Methods：

Additional 6 subjects will be recruited at this dose level 60mg to further confirm the safety and tolerability of RP2D. Eligible pts were treated with 6 cycles of rituximab (375mg/m2 on day 1), lenalidomide (25mg on d1-10) and selinexor (dose level: 60mg, on days 1, 8,15 of each 28-day cycle), followed by selinexor and lenalidomide maintenance until disease progression. Dose limiting toxicities (DLT) was defined as the occurrence of severe toxicities during the first cycle: grade 3 febrile neutropenia> 5 days, grade 4 neutropenia or thrombocytopenia >7 days, grade 3/4 thrombocytopenia with hemorrhage, or any grade 3 non-hematologic toxicity >7 days.

Results:

From May 2022 to April 2023, 16 pts were enrolled and no DLT occurred. At baseline in these 16 pts, refractory to last line was 93.75% and primary refractory was 68.75%. Among 12 efficacy evaluable pts, 3 pts achieved complete response (CR), 5 pts achieved partial response (PR) and another 4 pts achieved progressive disease (PD). Most AEs were grade 1 or 2 and were reversible with supportive care or dose modification. At data cutoff (June 1, 2023), 7 pts were still receiving treatment and no pts came off study due to intolerability or AEs. Median PFS and median DOR were 11.2 months and not reached.

Conclusion：

Selinexor in combination with lenalidomide and rituximab showed encouraging preliminary efficacy and generally tolerable toxicity with an ORR of 66.7%, CR of 25% and median PFS 11.2 months in all evaluable dose level pts, and with an ORR of 80% and CR of 20% in evaluable selinexor 60mg dose (RP2D). This study is currently enrolling patients in the dose expansion group.

No relevant conflicts of interest to declare.

Selinexor, a selective inhibitor of nuclear export has been approved by the US Food and Drug Administration for the treatment of R/R DLBCL. We want to ehvaluating the safety and tolerability of selinexor in combination with R2 for R/R DLBCL and iNHL.

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2023
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