A phase II trial of larotrectinib in tumors with NTRK fusions or extremes of NTRK mRNA overexpression identified by comprehensive genomic profiling.

Background: TRK-inhibitors have demonstrated efficacy across several cancers with NTRK fusions. Their activity in cancers with NTRK overexpression remains unclear.

Methods: This trial enrolled patients with advanced cancers harboring NTRK fusions or extreme mRNA overexpression, defined as NTRK1/2/3 expression by RNA profiling >5 SDs for a given cancer type.

Oral Etoposide for Relapsed or Refractory Ewing Sarcoma in Adolescent and Adult Patients.

Prognosis remains poor for patients with relapsed or refractory Ewing sarcoma, with limited treatment options after first-line therapy. Oral etoposide has efficacy in the paediatric setting; however, data are limited in adults. A retrospective analysis was conducted on 33 patients with relapsed or refractory Ewing sarcoma who completed at least one cycle of oral etoposide at the Peter MacCallum Cancer Centre from 2005 to 2020.

The 5-factor modified frailty index as a prognostic factor following stereotactic radiosurgery for metastatic disease to the brain from non-small cell lung cancer: A multi-center cohort analysis.

Background: Non-small cell lung cancer (NSCLC) patients often develop brain metastases (BMs), complicating management. We have shown that increasing frailty is associated with decreased overall survival (OS) and central nervous system progression free survival (PFS) for patients undergoing stereotactic radiosurgery (SRS) to BMs. Leveraging the International Radiosurgery Research Foundation, we sought to expand upon these findings, in NSCLC specifically.

Phase 1/2 Study of the Indoleamine 2,3-Dioxygenase 1 Inhibitor Linrodostat Mesylate Combined With Nivolumab or Nivolumab and Ipilimumab in Advanced Solid Tumors or Hematologic Malignancies.

Purpose: To evaluate linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies.

Patients And Methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion], 100 or 200 mg) plus nivolumab (480 mg every [Q] 4 weeks [W] or 240 mg Q2W) or triplet therapy (part 3, linrodostat 20-100 mg QD; nivolumab 360 mg Q3W or 480 mg Q4W; ipilimumab 1 mg/kg Q6W or Q8W). Endpoints included safety and efficacy (co-primary; parts 2, 3), pharmacokinetics, pharmacodynamics, biomarkers, and efficacy (part 1).