Abstract 839P
Background
Rebastinib is a switch control inhibitor of TIE2 kinase. TIE2 is expressed in endothelial cells and in some 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 80 mg/m2. In part 1, we observed antitumor activity across multiple tumor types (5 PRs in 24 pts at 50 mg BID and 3 PRs in 19 pts at 100 mg BID), including 3 PRs in platinum-resistant ovarian cancer (PROC). Part 2 has 5 cohorts: TNBC, inflammatory breast cancer, PROC, endometrial cancer and carcinosarcoma. Here, we present preliminary results from the PROC cohort.
Methods
Part 2 is a Simon 2-stage design enrolling 18 pts into the first stage, and if ≥5 responses, an additional 15 pts in the second stage. Pts were treated with rebastinib in combination with paclitaxel 80 mg/m2 intravenous weekly (D1, D8, D15 of repeated 28-day cycles) and evaluated for safety (CTCAE v5.0) and efficacy (RECIST v1.1).
Results
As of March 20, 2020, 20 pts were enrolled; the median age was 58 years. All received ≥ 1 prior regimen with paclitaxel/carboplatin; the median number of prior therapies was 5 (2, 7). Ten pts were initially treated with 100 mg BID rebastinib (reduced to 50 mg BID due to muscular weakness [4 pts in this cohort]) and 10 pts with 50 mg BID with a treatment median duration of 16 weeks (0.7, 31.9). In 17 evaluable pts, there were 5 PRs and 9 SDs (at 8 weeks) for an ORR of 29% and CBR of 82%. In addition, 8/13 (62%) pts had a CA-125 response. TEAEs (≥n=5) were mostly ≤ grade 2, including fatigue (n=8), nausea (n=8), diarrhea, dry mouth, peripheral sensory neuropathy, vomiting (n=6 each); abdominal pain, alopecia, constipation, peripheral edema and stomatitis (n=5 each). Serious AEs possibly related to rebastinib included grade 2, reversible muscular weakness (at 100 mg BID with no additional occurrences at rebastinib 50 mg BID), fatigue and constipation (n=1 each).
Conclusions
The preliminary activity and safety of rebastinib at 50 mg BID in combination with weekly paclitaxel for heavily pretreated pts with PROC, all of whom received prior carboplatin/paclitaxel, is encouraging. Simon stage 2 enrollment is ongoing.
Clinical trial identification
NCT03601897.
Editorial acknowledgement
Legal entity responsible for the study
Deciphera Pharmaceuticals, LLC.
Funding
Deciphera Pharmaceuticals, LLC.
Disclosure
E.P. Hamilton: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Black Diamond; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Acerta Pharma; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): ArQule; Research grant/Funding (institution): Arvinas; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution), Travel/Accommodation/Expenses: Clovis Oncology; Research grant/Funding (institution): Compugen; Research grant/Funding (institution): Curis; Research grant/Funding (institution): CytomX Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): eFFECTOR Therapeutics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: EMD Serono; Research grant/Funding (institution): Fochon; Research grant/Funding (institution): Fujifilm; Research grant/Funding (institution): G1 Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Research grant/Funding (institution): H3 Biomedicine; Research grant/Funding (institution): Harpoon; Research grant/Funding (institution): Hutchison MediPharma; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): InventisBio; Research grant/Funding (institution): Karyopharm Therapeutics; Research grant/Funding (institution): Leap Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Medivation; Advisory/Consultancy, Research grant/Funding (institution): Mersana; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Molecular Templates; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Nucana; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): Orinove; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Sermonix Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Silverback; Research grant/Funding (institution): Stem CentRx; Research grant/Funding (institution): Syros Pharmaceuticals; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): TapImmune Inc.; Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro; Research grant/Funding (institution): Torque; Research grant/Funding (institution): Unum Therapeutics; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zenith Epigenetics; Research grant/Funding (institution): Zymeworks; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Foundation Medicine; Travel/Accommodation/Expenses: Genzyme; Travel/Accommodation/Expenses: Guardant Health; Travel/Accommodation/Expenses: Helsinn Therapeutics; Travel/Accommodation/Expenses: HERON; Travel/Accommodation/Expenses: Lexicon; Travel/Accommodation/Expenses: Medivation; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Sysmex; Full/Part-time employment: Sarah Cannon Research Institute and Tennessee Oncology, LLC. S. Goel: Research grant/Funding (institution): Biegene; Research grant/Funding (institution): Oncolytics; Licensing/Royalties, A co-inventor of Patent No. 20090258364: Patent. R. Arend: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Tesaro; Advisory/Consultancy: VBL Therapeutics; Advisory/Consultancy: Leap Therapeutics. D.L. Richardson: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Ipsen; Advisory/Consultancy, Research grant/Funding (institution): Mersana; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): ArQule, Inc; Research grant/Funding (institution): Deciphera; Research grant/Funding (self): Five Prime Therapeutics; Research grant/Funding (institution): Harpoon therapeutics; Research grant/Funding (institution): Innovent Biologics; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Syros Pharmaceuticals. J.R. Diamond: Advisory/Consultancy, Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Millennium; Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Research grant/Funding (institution): Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses: MedImmune; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Rexahn Pharmaceuticals; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): OnKure. F. Janku: Advisory/Consultancy, Research grant/Funding (institution): Deciphera Pharmaceuticals, LLC; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Ideaya Biosciences; Advisory/Consultancy: IFM Therapeutics; Advisory/Consultancy: Immunomet; Advisory/Consultancy: Jazz Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: PureTech; Advisory/Consultancy: Sequenom; Advisory/Consultancy: Sotio; Advisory/Consultancy: Synlogic; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Cardiff Oncology; Advisory/Consultancy: Valeant/Dendreon; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Asana Biosciences; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): BioMed Valley Discoveries; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Fujifilm; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Piqur; Research grant/Funding (institution): Plexxikon; Research grant/Funding (institution): Proximagen; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Symphogen; Non-remunerated activity/ies: Bio-Rad; Research grant/Funding (institution): Astex Pharmaceuticals. C. Matthews: Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Syros; Research grant/Funding (institution): Tesaro/GSK. L. JeBailey, H. Achour: Shareholder/Stockholder/Stock options, Full/Part-time employment: Deciphera Pharmaceuticals, LLC. K. Kuida: Shareholder/Stockholder/Stock options, Full/Part-time employment: Deciphera Pharmaceuticals, LLC; Shareholder/Stockholder/Stock options: Vertex Pharmaceuticals. R. Ruiz-Soto: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, An inventor in pending patents at Deciphera. I have transferred the rights to Deciphera: Deciphera Pharmaceuticals, LLC; Shareholder/Stockholder/Stock options, Licensing/Royalties, 3 patents with Immunogen; I transferred the rights to Immunogen. No royalties.: Immunogen. J. Hays: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Deciphera; Advisory/Consultancy: Ipsen. All other authors have declared no conflicts of interest.