Alpha-T: An innovative decentralized (home-based) phase 2 trial of alectinib in ALK-positive (ALK+) solid tumors in a histology-agnostic setting.

TPS3155 Background: Anaplastic lymphoma kinase ( ALK) fusions are found in 3–8% of non-small cell lung cancers (NSCLC) and ̃0.2% of other tumor types. Alectinib is a selective, CNS-active ALK tyrosine kinase inhibitor approved as first-line treatment for adults with advanced ALK fusion-positive ( ALK-fp) NSCLC based on the phase 3 ALEX trial (NCT02075840; PMID 28586279). Preliminary evidence supports investigation of alectinib in a tumor-agnostic setting. ALK inhibitors have shown efficacy in ALK-fp tumor types other than NSCLC (PMIDs 29685646; 28977547; 30591488), with alectinib showing efficacy irrespective of ALK fusion partner and against ALK-activating mutations (PMIDs 29642598; 29559559). Methods: Alpha-T is a phase 2 open-label, single-arm trial (NCT04644315) with an innovative home-based remote design, currently enrolling adults with histologically confirmed, locally advanced/metastatic solid tumors (except lung cancer and cancers of unknown primary) harboring ALK fusions or selected mutations ( ALK-mut; R1275Q, F1245C, F1174X). The decentralized design permits enrollment regardless of location, allows most assessments to be home-based and maintains the relationship between patients (pts) and their treating oncologist. Key inclusion criteria: no alternative or unsuitable to receive standard therapy; ECOG PS 0–2; adequate hematologic, renal and hepatic functions; no prior ALK inhibitor; measurable solid tumor (RECIST 1.1) or primary brain tumor (RANO); asymptomatic or stable CNS metastases permitted. Pts are identified via the Foundation Medicine Inc. (FMI) Precision Enrollment service. For any solid tumor identified as ALK+ (fusion/selected mutation) by next-generation sequencing in tissue/blood (F1 CDx/F1L CDx, FMI), the ordering oncologist is given trial details and can liaise with a Science 37 investigator. Pts receive 600mg oral alectinib twice a day with food until radiological PD, unacceptable toxicity, withdrawal of consent or death. Home-based assessments (eg, physical examination, blood sampling, questionnaire completion) are conducted in-person by a mobile nurse at baseline and every 4 weeks, with remote support from the Science 37 investigator via their telemedicine platform. Tumor assessments at screening and every 8 weeks are performed at a local radiology facility. Primary endpoint: confirmed ORR by investigator in pts with ALK-fp tumors (RECIST 1.1). Secondary endpoints: ORR by independent review facility (IRF); DoR and PFS; intracranial ORR and DoR (IRF); OS and safety. Descriptive analyses are planned for pts with ALK-mut tumors and primary brain tumors. Pharmacokinetics and biomarkers will be evaluated. Patient-reported outcomes will be assessed via the EORTC QLQ-C30 and EuroQoL EQ-5D-5L questionnaires. Target enrollment is 50 pts with ALK-fp tumors evaluable by RECIST. As of 9 Feb 2021, 1 pt is in screening. Clinical trial information: NCT04644315.