Selinexor in Combination With Weekly Paclitaxel in Patients With Metastatic Solid Tumors: Results of an Open Label, Single-Center, Multi-Arm Phase 1b Study With Expansion Phase in Ovarian Cancer

Authors

Shannon N Westin
Siqing Fu
Apostolia Tsimberidou
Sarina Piha-Paul
Fechukwu Akhmedzhanov
Bulent Yilmaz
Lacey McQuinn
Amanda L Brink
Jing Gong
Cheuk Hong Leung
Heather Lin
David S Hong
Shubham Pant
Brett Carter
Amir Jazaeri
David Gershenson
Anil K Sood
Robert L Coleman
Jatin Shah
Funda Meric-Bernstam
Aung Naing

Publication Date

1-1-2023

Journal

Gynecologic Oncology

Abstract

OBJECTIVE: Selinexor is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound which blocks Exportin-1 (XPO1). Our objective was to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel.

METHODS: This was an open label, single-center, multi-arm phase 1b study utilizing a "3 + 3" design and a "basket-type" expansion in recurrent solid tumors. Selinexor (60 mg or 80 mg twice weekly orally) and weekly paclitaxel (80 mg IV 2 week on, 1 week off) were one of 13 parallel arms. Efficacy was evaluated using RECIST version 1.1.

RESULTS: All 35 patients treated were evaluable for toxicity and 31 (88%) were evaluable for response. Patient diagnoses included platinum-resistant/refractory ovarian (n = 28), breast (n = 4), prostate (n = 2), and cervical (n = 1) cancer. Patients had a median of four prior therapies (range 1-10), and 47% had a prior taxane in the recurrent setting. There were no DLTs and 60 mg was chosen as the RP2D due to long-term tolerability. Ninety-seven percent of patients had at least one treatment-emergent adverse event (TEAE), and the most common grade ≥ 3 TEAE were neutropenia (46%), anemia (31%), and nausea (21%). Among 24 evaluable patients with ovarian cancer, response rate was 17%, CBR was 58%, and median PFS was 6.8 months (95% CI 3.7, not reached (NR)).

CONCLUSIONS: Oral selinexor in combination with weekly paclitaxel demonstrated promising clinical activity with manageable toxicity. This combination should be considered for further exploration in a randomized study, especially in ovarian malignancies.

Keywords

Male, Humans, Female, Paclitaxel, Neoplasm Recurrence, Local, Ovarian Neoplasms, Hydrazines, Neoplasms, Second Primary, Antineoplastic Combined Chemotherapy Protocols

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Associated Data

PMID: 36423446