Abstract 728P
Background
Rebastinib is a switch-control inhibitor of TIE2 kinase. TIE2 is expressed in endothelial cells and certain macrophages with pro-angiogenic, pro-metastatic, and immunosuppressive properties associated with chemotherapy resistance. This is a 2-part, open-label, phase Ib/II study with orally administered rebastinib in combination with weekly paclitaxel. In part 1, we observed antitumor activity across multiple tumor types, including 3 partial responses (PRs) in platinum-resistant ovarian cancer (PROC). Part 2 included 5 cohorts of different cancer types including PROC. Here we provide updated results (ESMO 2020) from the fully enrolled PROC cohort.
Methods
Part 2 is a Simon 2-stage design enrolling 18 patients (pts) into the first stage, and if ≥5 responses, an additional 15 pts in the second stage. Pts were treated with 100 or 50 mg rebastinib twice daily (BID) plus weekly intravenous paclitaxel 80 mg/m2 (D1, D8, D15 of repeated 28-day cycles) and evaluated for safety and efficacy.
Results
As of March 19, 2021, 38 pts were enrolled; median age was 60 years. All received ≥1 prior regimen with paclitaxel/carboplatin; median number (range) of prior regimens was 4 (2, 7). Of 10 pts treated with rebastinib 100 mg BID, 7 were reduced to 50 mg BID; an additional 28 pts were treated with 50 mg BID. Median (range) treatment duration was 6.1 months (0.5, 14.7). In 34 evaluable pts, there were 1 CR, 11 PRs, and 19 SDs for an objective response rate of 35% (confirmed + unconfirmed) and a 16-week clinical benefit rate of 79%. Additionally, 19 of 26 evaluable pts (73%) had a CA-125 response. TEAEs (≥25%) were mostly Grade ≤2, including fatigue (53%), alopecia (42%), dry mouth, peripheral sensory neuropathy, peripheral edema (each 37%), nausea (34%), constipation (32%), diarrhea, hypertension, abdominal pain (each 29%), and reversible muscular weakness (RMW; 26%). SAEs related to rebastinib included RMW (n=2), fatigue, urinary tract infection, and constipation (n=1 each).
Conclusions
These updated results of rebastinib at 50 mg BID in combination with paclitaxel showed encouraging preliminary antitumor activity and a manageable safety profile in heavily pretreated PROC patients, and supports further development in patients with PROC.
Clinical trial identification
NCT03601897.
Editorial acknowledgement
Editorial writing support was provided by Atreju Lackey, PhD, of AlphaBioCom, Llc, King of Prussia, PA.
Legal entity responsible for the study
Deciphera Pharmaceuticals, Llc.
Funding
Pharmaceutical, biotech or other commercial company.
Disclosure
E.P. Hamilton: Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Dantari; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Puma Biotechnology; Financial Interests, Personal, Advisory Role: Silverback Therapeutics; Financial Interests, Personal, Advisory Role: CytomX; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Mersana; Financial Interests, Personal, Advisory Role: Black Diamond; Financial Interests, Personal, Advisory Role: H3 Biomedicine; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Arvinas; Financial Interests, Personal, Advisory Role: Deciphera Pharmaceuticals; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Full or part-time Employment: Sarah Cannon Research Institute, Tennessee Oncology, LLC; Financial Interests, Institutional, Research Grant: OncoMed; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Zymeworks; Financial Interests, Institutional, Research Grant: Rgenix; Financial Interests, Institutional, Research Grant: ArQule; Financial Interests, Institutional, Royalties: Clovis; Financial Interests, Institutional, Research Grant: Silverback Therapeutics; Financial Interests, Institutional, Research Grant: Millennium; Financial Interests, Institutional, Research Grant: Acerta Pharma; Financial Interests, Institutional, Research Grant: Sermonix Pharmaceuticals; Financial Interests, Institutional, Research Grant: Torque; Financial Interests, Institutional, Research Grant: Black Diamond; Financial Interests, Institutional, Research Grant: Karyopharma; Financial Interests, Institutional, Research Grant: Infinity Pharmaceuticals; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: Syndax; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: FujiFilm; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Fochon; Financial Interests, Institutional, Research Grant: Molecular Templates; Financial Interests, Institutional, Research Grant: Onconova Therapeutics; Financial Interests, Institutional, Research Grant: Dana Farber Cancer Hospital; Financial Interests, Institutional, Research Grant: Hutchinson MediPharma; Financial Interests, Institutional, Research Grant: MedImmune; Financial Interests, Institutional, Research Grant: SeaGen; Financial Interests, Institutional, Research Grant: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Compugen; Financial Interests, Institutional, Research Grant: TapImmune; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: H3 Biomedicine; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Arvinas; Financial Interests, Institutional, Research Grant: StemCentRx; Financial Interests, Institutional, Research Grant: Verastem; Financial Interests, Institutional, Research Grant: eFFECTOR Therapeutics; Financial Interests, Institutional, Research Grant: CytomX; Financial Interests, Institutional, Research Grant: InventisBio; Financial Interests, Institutional, Research Grant: Lycera; Financial Interests, Institutional, Research Grant: Mersana; Financial Interests, Institutional, Research Grant: Radius Health; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Nucana; Financial Interests, Institutional, Research Grant: Leap Therapeutics; Financial Interests, Institutional, Research Grant: Zenith Epigenetics; Financial Interests, Institutional, Research Grant: Harpoon; Financial Interests, Institutional, Research Grant: Orinove; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Syros; Financial Interests, Institutional, Research Grant: Sutro; Financial Interests, Institutional, Research Grant: G1 Therapeutics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Olema; Financial Interests, Institutional, Research Grant: Polyphor; Financial Interests, Institutional, Research Grant: Immunogen; Financial Interests, Institutional, Research Grant: Plexxicon; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Akesobio Australia; Financial Interests, Institutional, Research Grant: Shattuck Labs. S. Goel: Financial Interests, Personal, Royalties, Co-inventor of Patient No. 20090258364: Montefiore Medical Center. R. Arend: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: VBL Therapeutics; Financial Interests, Personal, Advisory Role: Leap Therapeutics. D.L. Richardson: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Mersana; Financial Interests, Personal, Advisory Role: Tesaro/GlaxoSmithKline; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Mersana; Financial Interests, Institutional, Research Grant: Tesaro/GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Aravive; Financial Interests, Institutional, Research Grant: ArQule, Inc.; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Harpoon Therapeutics; Financial Interests, Institutional, Research Grant: Innovent Biologics; Financial Interests, Institutional, Research Grant: Karyopharm; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Syros Pharmaceuticals; Financial Interests, Institutional, Research Grant: Five Prime Therapeutics; Financial Interests, Institutional, Research Grant: Hookipa Biotech; Financial Interests, Institutional, Research Grant: FujiFilm; Financial Interests, Institutional, Research Grant: Shattuck Labs; Financial Interests, Institutional, Research Grant: Plexxikon. B. Corr: Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Novocure; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Institutional, Research Grant: Clovis. F. Janku: Financial Interests, Personal, Advisory Role: Bicara; Financial Interests, Personal, Advisory Role: Illumina; Financial Interests, Personal, Advisory Role: Ideaya Biosciences; Financial Interests, Personal, Advisory Role: IFM Therapeutics; Financial Interests, Personal, Advisory Role: Synlogic; Financial Interests, Personal, Advisory Role: Sotio; Financial Interests, Personal, Advisory Role: Puretech Health; Financial Interests, Personal, Advisory Role: Petra Pharma; Financial Interests, Personal, Advisory Role: FORE; Financial Interests, Personal, Advisory Role: Cardiff Oncology; Financial Interests, Personal, Advisory Role: Immunoment; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: BioMed Valley Discoveries; Financial Interests, Institutional, Research Grant: Astex; Financial Interests, Institutional, Research Grant: Agios; Financial Interests, Institutional, Research Grant: Bicara; Financial Interests, Institutional, Research Grant: Bioxcel Therapeutics; Financial Interests, Institutional, Research Grant: FORE; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Symphogen; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Asana; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Ideaya Biosciences; Financial Interests, Institutional, Research Grant: JS Innopharm; Financial Interests, Institutional, Research Grant: Synthorx; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: F-star Therapeutics; Financial Interests, Institutional, Research Grant: SQZ Biotechnologies; Financial Interests, Institutional, Research Grant: Synlogic; Financial Interests, Institutional, Research Grant: FujiFilm Pharmaceuticals; Financial Interests, Institutional, Research Grant: Sotio; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Puretech Health; Financial Interests, Institutional, Research Grant: NextCure; Financial Interests, Personal, Ownership Interest: Cardiff Oncology; Non-Financial Interests, Personal, Other: Bio-Rad. J. Hays: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Merck; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Tesaro. M. Michenzie: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals. W. Reichmann: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals. H. Achour: Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, Llc; Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, Llc. M.L. Sherman: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals; Financial Interests, Personal, Member of the Board of Directors: Pieris Pharmaceuticals. R. Ruiz-Soto: Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals. C. Mathews: Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Syros; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Tesaro/GSK; Financial Interests, Institutional, Research Grant: Moderna; Financial Interests, Institutional, Research Grant: Regeneron. All other authors have declared no conflicts of interest.