The Food and Drug Administration officially approved tepotinib (Tepmetko, EMD Serono, Inc.) on February 15, 2024, for adult patients with metastatic non-small cell lung cancer (NSCLC) that had mesenchymal-epithelial transition (MET) exon 14 skipping mutations.
Tepotinib received accelerated clearance for this use on February 3, 2021, after showing positive results in the VISION trial (NCT02864992), which was a multicenter, non-randomized, open-label, multicohort research. The transition to conventional approval was made after including 161 more patients and extending the follow-up period by 28 months to evaluate the duration of response.
Effectiveness was proven in 313 individuals with metastatic non-small cell lung cancer (NSCLC) carrying MET exon skipping mutations. Patients were administered a daily dose of 450 mg of tepotinib until disease progression or unacceptable toxicity occurred.
The main effectiveness criteria were Objective Response Rate (ORR) and Duration of Response (DOR), assessed by a Blinded Independent Review Committee. Out of 164 patients who had not had treatment before, the Objective Response Rate (ORR) was 57% with a 95% Confidence Interval (CI) of 49 to 65. Among the responders, 40% had a Duration of Response (DOR) of 12 months or more. Out of 149 patients who had received treatment before, the Objective Response Rate (ORR) was 45% with a 95% Confidence Interval (CI) of 37 to 53. Additionally, 36% of the responders had a Duration of Response (DOR) of 12 months or more.
The predominant adverse effects (≥20%) included edema, nausea, exhaustion, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.
The suggested dose of tepotinib is 450 mg taken orally once a day with meals.
Targeting FGFR4 and CD276 with CAR T-cells demonstrates a strong antitumor impact against children rhabdomyosarcoma
Chimeric antigen receptor (CAR) T-cells that specifically target Fibroblast Growth Factor Receptor 4 (FGFR4), a surface tyrosine receptor that is extensively expressed in rhabdomyosarcoma (RMS), are now undergoing clinical research. However, the effectiveness of these CAR T-cells may be hindered by tumor heterogeneity and inadequate activation. In this study, we present a method to enhance the co-stimulatory and targeting characteristics of a FGFR4 CAR through an optimization process. We substituted the hinge and transmembrane domain of CD8 as well as the 4-1BB co-stimulatory domain with the corresponding domains of CD28. The CARs produced exhibit heightened anti-tumor efficacy in multiple RMS xenograft models, with the exception of the RMS559 cell line, which is known for its aggressive nature.
