Clinical trial · Interventional
A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2)
A Phase II, Two-arm Study to Investigate Tepotinib Combined With Osimertinib in MET Amplified, Advanced or Metastatic NSCLC Harboring Activating EGFR Mutations and Having Acquired Resistance to Prior Osimertinib Therapy (INSIGHT 2)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This study was to assess the antitumor activity, safety, tolerability, and pharmacokinetics (PK) of the Mesenchymal-epithelial Transition Factor (MET) inhibitor tepotinib combined with the 3rd generation EGFR inhibitor osimertinib in participants with advanced or metastatic non-small cell lung cancer (NSCLC).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Non-small Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Osimertinib | Drug | Osimertinib | ALIAS |
| Tepotinib | Drug | Tepotinib | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Tepotinib and Osimertinib
- description
- Participants received a single oral dose of Tepotinib 500 milligrams (mg) followed by Omisertinib 80 mg once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
- interventionNames
- Drug: Tepotinib
- Drug: Osimertinib
- type
- EXPERIMENTAL
- label
- Tepotinib Mono-therapy
- description
- Participants received a single oral dose of Tepotinib 500 mg until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
- interventionNames
- Drug: Tepotinib
Primary outcomes (2)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) histology (confirmed by either histology or cytology) with documented activating Epidermal Growth Factor Receptor (EGFR) mutation * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks * Acquired resistance on previous first-line osimertinib. Participants must meet both of the following 2 criteria: * Radiological documentation of disease progression on first-line osimertinib * Objective clinical benefit documented during previous osimertinib therapy, defined by either partial or complete radiological response, or durable stable disease (SD) (SD should last greater than (\>) 6 months after initiation of osimertinib * Have received only first-line osimertinib as a prior line of therapy in the non curative advanced or metastatic NSCLC setting * MET amplification as determined by either FISH testing (central or local) on tumor tissue (TBx) or central blood-based next generation sequencing (LBx). Tumor and blood samples must be collected following progression on prior first-line osimertinib at Prescreening * Submission of tumor tissue and blood sample obtained after progression on first-line osimertinib, is mandatory for all patients for MET amplification testing * Submission of tumor tissue during Prescreening or Screening is mandatory for patients with tumor tissue tested by local FISH, to confirm MET amplification status. Central confirmation is not mandated prior to the start of study treatment * Other protocol defined inclusion criteria could apply Exclusion Criteria: * Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention * Any unresolved toxicity Grade 2 or more according to National cancer institute common terminology criteria for adverse events( NCI-CTCAE) version 5, from previous anticancer therapy with the exception of alopecia * Inadequate hematological, liver and renal function * Impaired cardiac function * History of interstitial lung disease(ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment * Hypertension uncontrolled by standard therapies (not stabilized to \< 150/90 millimeter of mercury (mmHg) * Contraindication to the administration of osimertinib * Other protocol defined exclusion criteria could apply.
References
Publications (3)
- BACKGROUNDF Smit E, Dooms C, Raskin J, Nadal E, Tho LM, Le X, Mazieres J, S Hin H, Morise M, W Zhu V, Tan D, H Holmberg K, Ellers-Lenz B, Adrian S, Brutlach S, Schumacher KM, Karachaliou N, Wu YL. INSIGHT 2: a phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance. Future Oncol. 2022 Mar;18(9):1039-1054. doi: 10.2217/fon-2021-1406. Epub 2021 Dec 17. PMID 34918545
- BACKGROUNDWu YL, Guarneri V, Voon PJ, Lim BK, Yang JJ, Wislez M, Huang C, Liam CK, Mazieres J, Tho LM, Hayashi H, Nhung NV, Chia PL, de Marinis F, Raskin J, Zhou Q, Finocchiaro G, Le AT, Wang J, Dooms C, Kato T, Nadal E, Hin HS, Smit EF, Wermke M, Tan D, Morise M, O'Brate A, Adrian S, Pfeiffer BM, Stroh C, Juraeva D, Strotmann R, Goteti K, Berghoff K, Ellers-Lenz B, Karachaliou N, Le X, Kim TM; INSIGHT 2 investigators. Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2024 Aug;25(8):989-1002. doi: 10.1016/S1470-2045(24)00270-5. PMID 39089305
- BACKGROUNDHallick J, Baird AM, Falchook G, Le X, Hong D, Viteri S, Raskin J, Reinmuth N, Vlassak S, Militaru M, Paik PK. Plain language summary of the development of tepotinib: a treatment for a subtype of non-small cell lung cancer called MET exon 14 skipping. Future Oncol. 2023 Mar;19(10):683-696. doi: 10.2217/fon-2022-1035. Epub 2023 Mar 31. PMID 36999526