Vandana G Abramson1, Mafalda Oliveira2, Andrés Cervantes3, Hans Wildiers4, Manish R Patel5,6, Todd M Bauer6, Philippe L Bedard7, Carlos Becerra8, Stephen Richey9, Michael C Wei10, Eric Reyner11, John Bond12, Na Cui13, Timothy R Wilson14, Heather M Moore14, Cristina Saura2, Ian E Krop15. 1. Vanderbilt University Medical Center, Nashville, TN, USA. vandana.abramson@vumc.org. 2. Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 3. CIBERONC, Medical Oncology Department, Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain. 4. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Louvain, Belgium. 5. Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, USA. 6. Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA. 7. Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada. 8. US Oncology Network, Texas Oncology, Dallas, TX, USA. 9. US Oncology Network, Texas Oncology, Fort Worth, TX, USA. 10. Product Development Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. 11. Department of Clinical Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. 12. PDSS-Global Safety Risk Management Oncology Group, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. 13. CStone Pharmaceuticals, Suzhou, China. 14. Oncology Biomarker Development, Genentech, Inc, 1 DNA Way, South San Francisco, CA, 94080, USA. 15. Dana-Farber Cancer Institute, Boston, MA, USA.
Abstract
PURPOSE: This open-label, phase Ib, dose-escalation, and dose-expansion study (NCT01862081) evaluated taselisib with a taxane in locally advanced or metastatic breast cancer (BC) and/or non-small cell lung cancer (NSCLC). METHODS: Patients received taselisib (2-6 mg tablet or 3-6 mg capsule) plus docetaxel or paclitaxel. Primary endpoints were safety, dose-limiting toxicities, maximum tolerated dose, and identification of a recommended phase II dose. Secondary endpoints included pharmacokinetics and antitumor activity assessment. RESULTS: Eighty patients (BC: 72; NSCLC: 7; BC/NSCLC: 1) were enrolled (docetaxel-receiving arms: 21; paclitaxel-receiving arms: 59). Grade ≥ 3 adverse events (AEs), serious AEs, and AEs leading to death were reported in 90.5%, 42.9%, and 14.3% of patients, respectively (docetaxel-receiving arms), and 78.9%, 40.4%, and 3.5% of patients, respectively (paclitaxel-receiving arms). Eight patients experienced dose-limiting toxicities. The maximum tolerated dose was exceeded with 3 mg taselisib (capsule) for 21 consecutive days plus 75 mg/m2 docetaxel and not exceeded with 6 mg taselisib (tablet) for 5 days on/2 days off plus 80 mg/m2 paclitaxel. Objective response rates and clinical benefit rates were 35.0% and 45.0%, respectively (docetaxel-receiving arms), and 20.4% and 27.8%, respectively (paclitaxel-receiving arms). Exposure for paclitaxel or docetaxel plus taselisib was consistent with the single agents. CONCLUSIONS: Taselisib in combination with a taxane has a challenging safety profile. Despite evidence of antitumor activity, the benefit-risk profile was deemed not advantageous. Further development is not planned.
PURPOSE: This open-label, phase Ib, dose-escalation, and dose-expansion study (NCT01862081) evaluated taselisib with a taxane in locally advanced or metastatic breast cancer (BC) and/or non-small cell lung cancer (NSCLC). METHODS:Patients received taselisib (2-6 mg tablet or 3-6 mg capsule) plus docetaxel or paclitaxel. Primary endpoints were safety, dose-limiting toxicities, maximum tolerated dose, and identification of a recommended phase II dose. Secondary endpoints included pharmacokinetics and antitumor activity assessment. RESULTS: Eighty patients (BC: 72; NSCLC: 7; BC/NSCLC: 1) were enrolled (docetaxel-receiving arms: 21; paclitaxel-receiving arms: 59). Grade ≥ 3 adverse events (AEs), serious AEs, and AEs leading to death were reported in 90.5%, 42.9%, and 14.3% of patients, respectively (docetaxel-receiving arms), and 78.9%, 40.4%, and 3.5% of patients, respectively (paclitaxel-receiving arms). Eight patients experienced dose-limiting toxicities. The maximum tolerated dose was exceeded with 3 mg taselisib (capsule) for 21 consecutive days plus 75 mg/m2 docetaxel and not exceeded with 6 mg taselisib (tablet) for 5 days on/2 days off plus 80 mg/m2 paclitaxel. Objective response rates and clinical benefit rates were 35.0% and 45.0%, respectively (docetaxel-receiving arms), and 20.4% and 27.8%, respectively (paclitaxel-receiving arms). Exposure for paclitaxel or docetaxel plus taselisib was consistent with the single agents. CONCLUSIONS:Taselisib in combination with a taxane has a challenging safety profile. Despite evidence of antitumor activity, the benefit-risk profile was deemed not advantageous. Further development is not planned.
Entities:
Keywords:
GDC-0032; Metastatic breast cancer; PI3K; PI3K inhibitor; PIK3CA; Taselisib