Reference Detail

Ref Type

PMID

Authors

E.P. Hamilton, S. Goel, R. Arend, C. Chu, D.L. Richardson, J.R. Diamond, V. John, F. Janku, C. Matthews, L. JeBailey, K. Kuida, H. Achour, R. Ruiz-Soto, J. Hays

Title

A phase Ib/II study of rebastinib and paclitaxel in advanced or metastatic platinum-resistant ovarian cancer

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	31	suppl_4

URL

https://www.sciencedirect.com/science/article/pii/S0923753420409743

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References