Phase Ib results of c-MET inhibitor ARQ 197 in combination with gemcitabine in a cohort of patients (pts) with advanced breast, ovarian, and uterine tumors.

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

Background: ARQ 197 is a non-ATP competitive selective inhibitor of c-MET. In vitro data suggest its synergy with gemcitabine. This study evaluates safety, pharmacokinetics (PK), biomarkers, and preliminary efficacy of the combination treatment in pts with advanced solid tumors. Here we present results of the cohort of pts with metastatic breast, ovarian, and uterine carcinoma.

Methods: Multicenter, phase Ib 3+3 dose escalation trial. Oral ARQ 197 administered at doses of 120-360 mg bid across different schedules (continuous vs. continuous with 1 week [wk] break every 2 or 3 wks) in combination with a fixed gemcitabine at 1,000 mg/m2/weekly 3 every 4 wks.

Results: As of January 4, 2011, a total of 32 pts with metastatic breast (12), ovarian (14), and uterine (6) carcinoma were enrolled in the study (ECOG 0:1 = 21:11; mean age 61, range 35-77 yrs; with median number of prior systemic therapies = 4 [1–9]). Seven pts had progressed to prior gemcitabine. Adverse events (AEs) considered at least possibly treatment-related were reported in 29 (91%) of these pts. Most commonly observed AEs (>10%) included thrombocytopenia (21; 66%, 4 G 3-4), anemia (21; 66%, 6 G 3-4), neutropenia (20; 63%, 7 G 3-4), fatigue (11; 34%, 3 G 3-4), nausea (9; 31%, 2 G 3-4), vomiting (6; 19%, 1 G 3-4), and leucopenia (4; 13%, 2 G 3-4). Three pts experienced treatment-related serious AEs (pancytopenia, thrombocytopenia, hypotension and interstitial lung disease, grade 3). Post-baseline tumor assessment was done in 27 evaluable pts; of them, 12 remained on study for >10 wks (mean 22; range 10-36), 5 (2 breast, 1 uterine, 2 ovarian) attained partial response (response rate 19%), and 15 demonstrated decline (4-87%) in tumor markers (CA15.3, CA125, CEA). In this study, 2 pts (ovarian and breast) with PR and 2 with SD (breast) had failed prior gemcitabine. Details on efficacy and scheduling will be presented.

Conclusions: Orally administered ARQ 197 at the MTD of 360 mg bid in combination with gemcitabine is generally well tolerated and shows encouraging signs of antitumor activity in the presented tumor types.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Journal of Clinical Oncology

DOI

https://doi.org/10.1200/jco.2011.29.15_suppl.3077

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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