Katy L Simonsen1, Paula M Fracasso2, Steven H Bernstein3, Megan Wind-Rotolo4, Manish Gupta5, Adriana Comprelli6, Timothy P Reilly7, Jim Cassidy8. 1. Global Biometric Sciences - Oncology, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: katy.simonsen@bms.com. 2. Oncology Development, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: Paula.Fracasso@bms.com. 3. Translational Sciences, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: sbernstein59@gmail.com. 4. Precision Medicine, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: Megan.Windrotolo@bms.com. 5. Clinical Pharmacology and Pharmacometrics - Oncology, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: mangumama@gmail.com. 6. Oncology Clinical Operations Strategy, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: Adriana.Comprelli@bms.com. 7. Oncology Development, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: Timothy.Reilly@bms.com. 8. Exploratory Clinical and Translational Research - Early Oncology Development, Bristol-Myers Squibb, Princeton, NJ, USA. Electronic address: jcassidy@celgene.com.
Abstract
BACKGROUND: The unprecedented success of immuno-oncology (I-O) agents targeting the cytotoxic T lymphocyte-associated antigen 4 and programmed death-1/programmed death-ligand 1 pathways has stimulated the rapid development of other I-O agents against novel immune targets. Bristol-Myers Squibb has designed a novel phase II platform trial, the Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) Program, to efficiently identify promising combinations for patients with specific malignancies. The concept and study design of the FRACTION Program-currently ongoing in patients with advanced non-small-cell lung cancer (FRACTION-Lung), gastric cancer (FRACTION-Gastric Cancer) and renal cell carcinoma (FRACTION-RCC)-are described. METHODS: The FRACTION Program comprises open-label, phase II studies that use adaptive randomisation designs with rolling combination regimens. Master Protocols provide the overall study design framework, whereas Sub-Protocols introduced over time provide details on specific I-O combination therapies to which patients may be randomised. In a Master Protocol, patients are enrolled into different Study Tracks based on characteristics such as prior I-O therapy experience. Patients who progress may be rerandomised to other combination regimens from any ongoing Sub-Protocol. Primary objectives are to assess objective response rate, median duration of response and progression-free survival rate at 24 weeks; the secondary objective is to investigate safety and tolerability. Biomarker collection before and on treatment will facilitate identification of patient subsets who benefit most from each therapy. CONCLUSIONS: The FRACTION Program allows for the evaluation of multiple I-O combinations through individual studies for specific tumours using an adaptive trial design and continuous enrolment.
RCT Entities:
BACKGROUND: The unprecedented success of immuno-oncology (I-O) agents targeting the cytotoxic T lymphocyte-associated antigen 4 and programmed death-1/programmed death-ligand 1 pathways has stimulated the rapid development of other I-O agents against novel immune targets. Bristol-Myers Squibb has designed a novel phase II platform trial, the Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) Program, to efficiently identify promising combinations for patients with specific malignancies. The concept and study design of the FRACTION Program-currently ongoing in patients with advanced non-small-cell lung cancer (FRACTION-Lung), gastric cancer (FRACTION-Gastric Cancer) and renal cell carcinoma (FRACTION-RCC)-are described. METHODS: The FRACTION Program comprises open-label, phase II studies that use adaptive randomisation designs with rolling combination regimens. Master Protocols provide the overall study design framework, whereas Sub-Protocols introduced over time provide details on specific I-O combination therapies to which patients may be randomised. In a Master Protocol, patients are enrolled into different Study Tracks based on characteristics such as prior I-O therapy experience. Patients who progress may be rerandomised to other combination regimens from any ongoing Sub-Protocol. Primary objectives are to assess objective response rate, median duration of response and progression-free survival rate at 24 weeks; the secondary objective is to investigate safety and tolerability. Biomarker collection before and on treatment will facilitate identification of patient subsets who benefit most from each therapy. CONCLUSIONS: The FRACTION Program allows for the evaluation of multiple I-O combinations through individual studies for specific tumours using an adaptive trial design and continuous enrolment.