Pooled Evaluation Exhibits Manageable Safety Profile With Tepotinib in MET Exon 14+ NSCLC

A pooled security evaluation of cohorts A and C from the part 2 VISION trial (NCT02864992) demonstrated that remedy with tepotinib (Tepmetko) was related to a excessive frequency of hostile results (AEs) in sufferers with MET exon 14–altered non–small cell lung most cancers (NSCLC), though the profile was thought of manageable.¹

Notably, these findings had been according to prior reviews from the trial. In the pooled security evaluation of cohorts A and C (n = 313), any-grade AEs occurred in 99.0% of sufferers, and grade 3 or increased AEs had been reported in 68.4% of sufferers. Treatment-related AEs (TRAEs) had been noticed in 91.7% of sufferers, together with grade 3 or increased TRAEs in 36.1% of sufferers. Any-grade critical AEs and critical TRAEs occurred in 54.6% and 16.0% of sufferers, respectively. AEs led to dose reductions in 33.2%, remedy interruptions in 43.8%, and everlasting discontinuation in 15.7% of sufferers. These charges of TRAEs had been 33.2%, 43.8%, and 15.7%, respectively. Additionally, 13.7% of sufferers skilled an AE that led to loss of life, 3 of which had been remedy associated.

The most typical TRAEs included peripheral edema (any-grade, 67.7%; grade ≥ 3, 11.8%), hypoalbuminemia (25.2%; 3.8%), nausea (23.3%; 0.6%), diarrhea (22.7%; 0.3%), elevated blood creatinine ranges (22.0%; 1.3%), alanine aminotransferase (ALT) stage elevation (14.1%; 2.2%), decreased urge for food (11.5%; 0.3%), aspartate aminotransferase stage elevation (11.2%; 1.9%), and amylase stage improve (10.5%; 1.9%).

In whole, 37.4% of sufferers required a minimum of 1 dose discount. The most typical any-grade TRAE resulting in dose discount, remedy interruption, and remedy discontinuation was peripheral edema (15.3%, 18.8%, and 6.1% of sufferers, respectively). Other TRAEs resulting in dose reductions had been generalized edema (3.2%), edema (2.2%), pleural effusion (1.6%), elevated blood creatinine ranges (2.6%), hypoalbuminemia (1.3%), fatigue (1.0%), asthenia (1.0%), and localized edema (1.0%). Other TRAEs resulting in remedy interruptions included elevated elevated blood creatinine ranges (5.8%), generalized edema (4.8%), edema (3.5%), pleural effusion (3.2%), elevated ALT ranges (2.6%), localized edema (2.2%), and nausea (2.2%). Other TRAEs resulting in remedy discontinuation included edema (1.3%), generalized edema (1.0%), pleural effusion (1.0%), interstitial lung illness (1.0%), and pneumonitis (1.0%).

Additionally, health-related high quality of life (HRQOL) patient-reported final result (PRO) scores remained secure with tepotinib use. Investigators noticed no significant change in European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) or EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores as much as 228 weeks. At the top of remedy, amongst sufferers evaluated for HRQOL, the imply change from baseline for the EORTC QLQ-C30 international well being standing (GHS) was –7.1 (commonplace deviation [SD], 26.66; n = 174), and the imply change for the EuroQol visible analogue scales (EQ-VAS) was –10 (SD, 23.7; n = 172); optimistic values signified enchancment. The imply modifications from baseline within the EORTC QLQ-lung most cancers (LC13) symptom scores for cough, dyspnea, and chest ache, respectively, had been –6.1 (SD, 28.16; n = 175), 7.1 (SD, 21.05; n = 175), and –2.3 (SD, 28.13; n = 174); unfavourable values signified enchancment. Furthermore, the median time to deterioration of the EORTC QLQ-LC13 symptom scores for cough, chest ache, and dyspnea had been 36.5 months, 30.4 months, and 5.5 months, respectively.

“Throughout the VISION trial, patients completed questionnaires evaluating their QOL before and while receiving tepotinib,” Enriqueta Felip, MD, PhD, lead examine writer and head of the Thoracic Cancer Unit at Hospital Universitari de la Vall d’Hebron in Barcelona, Spain, and coauthors defined within the conclusion of the poster presentation. “Overall, patients reported that health and QOL remained stable while receiving tepotinib. Specific scores relating to symptoms experienced by patients with lung cancer were improved during treatment for symptoms such as cough and chest pain, and remained stable for shortness of breath.”

What Was the Design of the VISION Trial of Tepotinib in Patients With MET-Altered NSCLC?

The VISION trial was a single-arm examine evaluating tepotinib in sufferers with superior NSCLC harboring MET exon 14 skipping alterations.² The examine evaluated tepotinib at a dose of 500 mg orally as soon as day by day and comprised 3 cohorts.

Eligible sufferers had been a minimum of 18 years of age, had histologically or cytologically confirmed NSCLC with MET exon 14 skipping alterations detected by liquid biopsy and/or tissue biopsy, measurable illness per RECIST 1.1 standards, and an ECOG efficiency standing of 0 or 1. Prior immunotherapy was permitted.

Patients had been excluded if their tumors harbored EGFR mutations or ALK rearrangements, if they’d obtained greater than 2 prior strains of systemic remedy, or if they’d prior publicity to MET or HGF inhibitors.

The main finish level of the examine was goal response price by impartial overview committee per RECIST 1.1 standards. Key secondary finish factors included length of response; progression-free survival; general survival; security; and PROs measured utilizing the EORTC QLQ-C30 GHS and 5 practical scales, EQ-5D-5L questionnaire with EQ-VAS, and EORTC QLQ-LC13 symptom scores (specializing in cough, dyspnea, and chest ache as predefined gadgets of curiosity). Scores ranged from 0 to 100, with a minimum of 10-point modifications from baseline thought of clinically significant.^1,2

The knowledge cutoff date for this evaluation was May 20, 2024.¹ PRO knowledge had been collected at baseline, on day 1 of remedy, each 6 weeks for the primary 9 months, and subsequently each 12 weeks throughout remedy. Time to deterioration was estimated by way of Kaplan-Meier methodology, outlined because the time from baseline to the primary clinically significant deterioration, with assessments repeated each 3 months. A mixed-model repeated measures evaluation was used to guage longitudinal modifications from baseline in EORTC QLQ-LC13 symptom scores.

What Were the Baseline Patient Demographics within the VISION NSCLC Trial?

The median age of sufferers with MET exon 14 skipping NSCLC was 72.0 years (vary, 41-94). In whole, 50.8% of sufferers had been feminine, 73.8% of sufferers had an ECOG efficiency standing of 1, and 47.6% of sufferers had obtained prior remedy.

The distribution of ECOG efficiency standing rating was skewed towards 1, noticed in 73.8% of sufferers, whereas 25.9% of sufferers had a rating of 0. At examine entry, 47.6% of sufferers had obtained a minimum of 1 prior systemic remedy. The median remedy length was 7.5 months (vary, 0.03-83.12 months), and 19 sufferers remained on tepotinib for a minimum of 48 months.

References

1. Felip E, Ferrara R, Veillon R, et al. Safety and patient-reported outcomes with tepotinib in sufferers with METex14 skipping NSCLC: ≥3 years follow-up of VISION. Presented at: 2025 IASLC World Conference on Lung Cancer; September 6-10, 2025; Barcelona, Spain. Poster P3.12.40.
2. Tepotinib part II in NSCLC harboring MET alterations (VISION). ScientificTrials.gov. Updated August 14, 2025. Accessed September 9, 2025.