Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Tepotinib + gefitinib in patients with EGFR-mutant NSCLC with MET amplification: final analysis of INSIGHT (#81)

Malinda Itchins 1 , Chong Kin Liam 2 , Azura Ahmad 3 , Te-Chun Hsia 4 , Janying Zhou 5 , Dong-Wan Kim 6 , Ross Andrew Soo 7 , Ying Cheng 8 , Shun Lu 9 , Sang Won Shin 10 , James Chih-Hsin Yang 11 , Yiping Zhang 12 , Jun Zhao 13 , Rolf Bruns 14 , Andreas Johne 15 , Yi-Long Wu 16
  1. North Shore Private Hospital, St Leonards, NSW, Australia
  2. Department of Medicine, Faculty of Medicine, University of Malaysia, Kuala Lumpur, Malaysia
  3. Beacon Hospital, Selangor, Malaysia
  4. China Medical University Hospital, Taichung City, Taiwan
  5. The First Affiliated Hospital, Zhejiang University, Hangzhou, China
  6. Seoul National University Hospital, Seoul, South Korea
  7. National University Cancer Institute, Singapore
  8. Jilin Province Cancer Hospital, Changchun, China
  9. Shanghai Chest Hospital, Shanghai, China
  10. Korea University Anam Hospital, Seoul, South Korea
  11. National Taiwan University Hospital, Taipei, Taiwan
  12. Zhejiang Cancer Hospital, Hangzhou, China
  13. Beijing Cancer Hospital, Beijing, China
  14. Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Germany
  15. Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Germany
  16. Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong, Academy of Medical Sciences, Guangzhou, China

 

Aims: We report the final analyses from the INSIGHT trial (NCT01982955; data cut-off: September 3, 2021; median follow-up: 57.5 months), which assessed the combination of tepotinib (a potent MET-TKI) and gefitinib versus chemotherapy in patients with EGFR-mutant NSCLC and resistance to anti-EGFR therapy due to MET amplification (METamp).

Methods: Patients with EGFR-mutant (T790M-negative) NSCLC and anti-EGFR resistance, with METamp (MET gene copy number [GCN] ≥5 and/or MET:CEP7 ≥2 by FISH) and/or MET overexpression (IHC 2+/3+), were randomized to tepotinib 500 mg (450 mg active moiety) + gefitinib 250 mg QD or chemotherapy. The primary endpoint was progression-free survival (PFS) per investigator assessment. Preplanned analyses evaluated patients with METamp.

Results: In 19/55 randomized patients (34.5%) with METamp (GCN ≥5, n=18; MET:CEP7 ≥2, n=13; MET IHC 3+, n=17), the median age was 60.4 years, 68.4% were never-smokers, and prior EGFR inhibitors were gefitinib (57.9%), afatinib (21.1%), erlotinib (10.5%), and icotinib (10.5%). The median duration of tepotinib + gefitinib treatment was 11.3 months (range: 1.1–56.5). Two patients continued treatment outside the study.

Tepotinib + gefitinib improved PFS (median 16.6 months [90% CI: 8.3, 22.1]) versus chemotherapy (median 4.2 months [90% CI: 1.4, 7.0]): HR 0.13 (90% CI: 0.04, 0.43). Overall survival (HR 0.10; 90% CI: 0.02, 0.36), objective response rate
(OR 2.67; 90% CI: 0.37, 19.56) and duration of response also improved with the combination in comparison to chemotherapy.

Treatment-related Grade ≥3 AEs occurred in seven patients (58.3%) with tepotinib + gefitinib and five (71.4%) with chemotherapy.

In patients with MET IHC 3+ (n=34, including 17 patients with METamp), tepotinib + gefitinib also markedly improved PFS (HR 0.35; 90% CI: 0.17, 0.74) and OS (HR 0.44; 90% CI: 0.23, 0.84) versus chemotherapy.

Conclusions: Tepotinib + gefitinib significantly improved PFS and OS versus chemotherapy in patients with EGFR-mutant NSCLC with METamp.