Biomarker-driven access to crizotinib in ALK-, MET-, or ROS1-positive malignancies in adults and children: Feasibility of the French National Acsé Program

Background: Crizotinib (czb) is registered only for the treatment of patients (pts) with ALK+ lung cancer. Czb targets (ALK, MET, ROS1) are also altered (translocation, amplification, mutation) in a wide range of malignancies in adults and children. To avoid off label use and allow for a nationwide safe and controlled access to czb for pts with an ALK, MET or ROS1 positive tumor, the French National Cancer Institute (INCa) launched the AcSé program: access to tumor molecular diagnosis in the 28 INCa molecular genetic centers along with an exploratory phase II trial. Methods: Biomarker identification is proposed to pts ≥ 1 year with an advanced disease among more than 15 malignancies (such as colon, gastric, liver, thyroid, renal and breast cancers, cholangiocarcinoma, lymphoma, neuroblastoma, sarcomas, and ROS1 or MET lung cancer) (such as colon, gastric, liver, thyroid, renal and breast cancers, cholangiocarcinoma, lymphoma, neuroblastoma, sarcomas, and ROS1 lung cancer) known from literature to harbor a genomic alteration in a czb target. If not eligible for any other academic or industry trial targeting the same alteration, a patient with an ALK, MET or ROS1 positive tumor may enter one of the 22 specified cohorts defined as a disease and a type of target alteration, and receives czb (adult: 250 mg x 2; child: 280 mg/m2 x 2). Pts with an altered czb target as evidenced through a pangenomic tumor profiling program are also eligible. Tumor response is evaluated every 2 months using RECIST criteria. Three statistical 2-stage designs are considered for cohorts to anticipate 3 situations in terms of expected response rate and incidence. Accrual stops if 0 response / N1 pts; else N2 additional pts are recruited. 10,000 to 15,000 molecular tests and 490 pts treated in 150 centers are planned over 3 years. From Aug. 2013 to Jan. 2014, 22 pts have been accrued. The AcSé program is currently being expanded to other targeted drugs. (Table presented).