Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Apr;40(2):290-299.
doi: 10.1007/s10637-021-01188-1. Epub 2021 Sep 25.

Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study

Kyaw Z Thein  1   2 , Daniel D Karp  3 , Apostolia Tsimberidou  3 , Jing Gong  3 , Selma Sulovic  3 , Jatin Shah  4 , Denái R Milton  5 , David S Hong  3 , Filip Janku  3 , Lacey McQuinn  3 , Bettzy A Stephen  3 , Rivka Colen  6 , Brett W Carter  7 , Timothy A Yap  3 , Sarina A Piha-Paul  3 , Siqing Fu  3 , Funda Meric-Bernstam  3 , Aung Naing  3
Affiliations
Clinical Trial

Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study

Kyaw Z Thein et al. Invest New Drugs. 2022 Apr.

Erratum in

Abstract

Background: Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies.

Methods: This was a single-center, multi-arm phase Ib study utilizing a "basket type" expansion. CT and selinexor was employed as one of the 13 parallel arms. Advanced relapsed/refractory solid tumors following standard therapy or where the addition of selinexor to standard regimens deemed appropriate, were eligible.

Results: Of 13 patients treated, 12 patients were evaluable for response. The most common cancers were breast (n = 4), esophageal (n = 2), ovarian (n = 2) and non-small cell lung cancers (n = 2). All 13 patients had at least one treatment-related adverse events (TRAEs) and the most common were neutropenia (85%), leukopenia (85%), thrombocytopenia (85%), anemia (69%), nausea (54%), vomiting (46%), and fatigue (46%). One patient at 60 mg QW experienced DLT with grade 3 nausea and vomiting lasting 3 days. Unconfirmed partial response (uPR) was observed in 3 patients; one patient each with esophageal, breast, and ovarian cancer. One patient with esophageal adenocarcinoma had confirmed PR, however, was discontinued from the study due to clinical progression. Five patients achieved stable disease (SD). Disease control rate was 8%. Majority of patients (77%), including two patients who had uPR, had prior exposure to carboplatin and/or paclitaxel. Time-to-treatment failure (TTF) ranged from 1 to 153 weeks.

Conclusion: The RP2D of selinexor was 60 mg QW in combination with CT. The combination conferred viable clinical activity with durable objective responses which should further be explored in tumor types for which CT is used as standard of care. Trial information.

Clinicaltrials: gov Identifier: NCT02419495. Sponsor(s): Karyopharm Therapeutics. (Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495 ).

Keywords: Carboplatin; Metastatic solid tumors; Paclitaxel; Selective inhibitor of nuclear export (SINE); Selinexor.

PubMed Disclaimer

Conflict of interest statement

Apostolia-Maria Tsimberidou has the following financial relationships to disclose: Research Funding (Institution): Immatics, Parker Institute for Cancer Immunotherapy, Tempus, OBI Pharma, EMD Serono, Baxalta, ONYX, Bayer, Boston Biomedical, Placon Therapeutics, Karus Therapeutics, and Tvardi Therapeutics. Consulting or Advisory Role: Covance, Genentech and Tempus.

Aung Naing reports research funding from NCI; EMD Serono; MedImmune; Healios Onc. Nutrition; Atterocor; Amplimmune; ARMO BioSciences; Eli Lilly; Karyopharm Therapeutics; Incyte; Novartis; Regeneron; Merck; BMS; Pfizer, CytomX Therapeutics; Neon Therapeutics; Calithera Biosciences; TopAlliance Biosciences; Kymab; PsiOxus; Arcus Biosciences; NeoimmuneTech; ImmuneOncia; Surface Oncology. On advisory board of CytomX Therapeutics; Novartis and Genome & Company; OncoSec KEYNOTE-695; STCube. Travel and accommodation expense from ARMO BioSciences. Spouse Research funding: Immune Deficiency Foundation, Jeffery Modell Foundation and chao physician-scientist, and Baxalta. Advisory board: Takeda, CSL, Behring, Horizon, and Pharming.

David S Hong reports Research/Grant Funding: AbbVie, Adaptimmune,Aldi-Norte, Amgen, Astra Zeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, GlaxoSmithKline, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati, miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle Genetics, Takeda, Turning Point Therapeutics. Travel, Accommodations, Expenses: Bayer, Genmab, AACR, ASCO, P.O.E.T, CCLO, SITC. Consulting or Advisory Role: Alpha Insights, Amgen, Axiom, Adaptimmune, Baxter, Bayer, eCancer, Genentech, GLG, Group H, Guidepoint, Infinity,Liberium, Medscape, Numab, Oncology Education Project Association, Pfizer, Prime Oncology, Takeda, Trieza, Therapeutics, WebMD. Other ownership interests: Molecular Match (Advisor), OncoResponse (Founder), Presagia Inc (Advisor).

Filip Janku reports Grant/Research Funding (Institutional): Novartis, Genentech, BioMed Valley Discoveries, Plexxikon, Deciphera, Piqur, Symphogen, Bayer, FujiFilm Corporation and Upsher-Smith Laboratories, Astex, Asana, Astellas, Agios, Proximagen, Bristol-Myers Squibb. Scientific Advisory Board: Deciphera, IFM Therapeutics, Synlogic, Guardant Health, Ideaya, PureTech Health. Paid Consultant: Trovagene, Immunomet, Jazz Pharmaceuticals, Sotio. Ownership Interests: Trovagene.

Funda Meric-Bernstam reports Consulting: Aduro BioTech Inc., Alkermes, AstraZeneca, DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., Genentech Inc., IBM Watson, Jackson Laboratory, Kolon Life Science, OrigiMed, PACT Pharma, Parexel International, Pfizer Inc., Samsung Bioepis, Seattle Genetics Inc., Tyra Biosciences, Xencor, Zymeworks. Advisory Committee: Immunomedics, Inflection Biosciences, Mersana Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Silverback Therapeutics, Spectrum Pharmaceuticals, Zentalis. Sponsored Research: Aileron Therapeutics, Inc. AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Millennium Pharmaceuticals Inc., Novartis, Puma Biotechnology Inc., Taiho Pharmaceutical Co. Honoraria: Chugai Biopharmaceuticals, Mayo Clinic, Rutgers Cancer Institute of New Jersey. Other (Travel Related): Beth Israel Deaconess Medical Center.

Sarina A. Piha-Paul receives Research/Grant Funding through the institution from the following sources: AbbVie, Inc.; ABM Therapeutics, Inc.; Acepodia, Inc; Alkermes; Aminex Therapeutics; Amphivena Therapeutics, Inc.; BioMarin Pharmaceutical, Inc; Boehringer Ingelheim; Bristol Myers Squib; Cerulean Pharma, Inc.; Chugai Pharmaceutical Co., Ltd; Curis, Inc.; Daiichi Sankyo; Eli Lilly; ENB Therapeutics; Five Prime Therapeutics; Gene Quantum; Genmab A/S; GlaxoSmithKline; Helix BioPharma Corp.; Incyte Corp.; Jacobio Pharmaceuticals Co., Ltd.; Medimmune, LLC.; Medivation, Inc.; Merck Sharp and Dohme Corp.; Novartis Pharmaceuticals; Pieris Pharmaceuticals, Inc.; Pfizer; Principia Biopharma, Inc.; Puma Biotechnology, Inc.; Rapt Therapeutics, Inc.; Seattle Genetics; Silverback Therapeutics; Taiho Oncology; Tesaro, Inc.; TransThera Bio; NCI/NIH; P30CA016672 – Core Grant (CCSG Shared Resources).

Siqing Fu reports clinical trial research funding paid to the institution from Eli Lilly, during the conduct of the study; and clinical trial research funding paid to the institution from AstraZeneca, Abbisko, Anaeropharma Science, Arrien Pharmaceuticals, BeiGene, BioAtla, LLC, Boehringer Ingelheim, Eli Lilly, Hookipa Biotech GmBH, Huya Bioscience International, IMV, Inc., Innovent Biologics, Co., Ltd., Lyvgen Biopharm, Co., Ltd., MacroGenics, Medivir AB, Millennium Pharmaceuticals, Inc., Nerviano Medical Sciences, NeuPharma, Inc., NIH/NCI, Novartis, OncoMed, Parexel International, LLC, Sellas Life Sciences Group, Soricimed Biopharma, Inc., Tolero Pharmaceuticals, all outside the submitted work.

Timothy A. Yap reports research support (to institution) from Artios, AstraZeneca, Bayer, Clovis, Constellation, Cyteir, Eli Lilly, EMD Serono, Forbius, F-Star, GlaxoSmithKline, Genentech, ImmuneSensor, Ipsen, Jounce, Karyopharm, Kyowa, Merck, Novartis, Pfizer, Ribon Therapeutics, Regeneron, Repare, Sanofi, Scholar Rock, Seattle Genetics, Tesaro, and Vertex Pharmaceuticals, and consultancy fees from Almac, Aduro, AstraZeneca, Atrin, Axiom, Bayer, Bristol-Myers Squibb, Calithera, Clovis, Cybrexa, EMD Serono, F-Star, Guidepoint, Ignyta, I-Mab, Janssen, Merck, Pfizer, Repare, Roche, Rubius, Schrodinger, Seattle Genetics, Varian and Zai Labs outside of the submitted work.

Jatin Shah is an employee of and stockholder of Karyopharm. All remaining authors have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
a Waterfall plot of maximum change in tumor measurements (per RECIST v1.1) for evaluable patients. b Kaplan-Meier plot showing progression free survival (PFS) for evaluable patients and overall survival (OS) for all treated patients
See this image and copyright information in PMC

References

    1. Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, Nishida E (1997) CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 390(6657):308–311. 10.1038/36894 - DOI - PubMed
    1. Xu D, Grishin NV, Chook YM (2012) NESdb: a database of NES-containing CRM1 cargoes. Mol Biol Cell 23(18):3673–3676. 10.1091/mbc.E12-01-0045 - DOI - PMC - PubMed
    1. Nguyen KT, Holloway MP, Altura RA (2012) The CRM1 nuclear export protein in normal development and disease. Int J Biochem Mol Biol 3(2):137–151 - PMC - PubMed
    1. Turner JG, Dawson J, Sullivan DM (2012) Nuclear export of proteins and drug resistance in cancer. Biochem Pharmacol 83(8):1021–1032. 10.1016/j.bcp.2011.12.016 - DOI - PMC - PubMed
    1. Benkova K, Mihalyova J, Hajek R, Jelinek T (2020) Selinexor, selective inhibitor of nuclear export: Unselective bullet for blood cancers. Blood Rev 100758. 10.1016/j.blre.2020.100758 - PubMed

Publication types

MeSH terms

Associated data