Tepotinib plus osimertinib in osimertinib-relapsed MET amplified NSCLC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Healthcare KGaA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Nov 2019 → 11 Dec 2024

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Healthcare KGaA

External identifiers

EU CT number

2024-512005-87-00

EudraCT number

2019-001538-33

ClinicalTrials.gov

NCT03940703

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacogenetic, Therapy, Safety, Efficacy, Pharmacokinetic

To assess the efficacy of tepotinib combined with osimertinib in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH."

Secondary objectives 5

1. To assess the efficacy of tepotinib combined with osimertinib in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification determined centrally by blood-based next generation sequencing.
2. To assess the efficacy of tepotinib monotherapy in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification determined centrally by FISH.
3. To assess tolerability and safety in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification treated with the combination of tepotinib plus osimertinib
4. To assess tolerability and safety in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification treated with tepotinib monotherapy.
5. To further assess efficacy of tepotinib combined with osimertinib in participants with advanced or metastatic EGFRm+ NSCLC and MET amplification, determined centrally by FISH please refer to protocol for more information

Conditions and MedDRA coding

Lung Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks
3. 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
4. Have received only first-line osimertinib as a prior line of therapy in the non curative advanced or metastatic NSCLC setting
5. 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
6. Submission of tumor tissue and blood sample obtained after progression on first-line osimertinib, is mandatory for all patients for MET amplification testing
7. 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

Exclusion criteria 7

1. Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention
2. 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
3. Inadequate hematological, liver and renal function
4. Impaired cardiac function
5. History of interstitial lung disease(ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment
6. Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 millimeter of mercury (mmHg)
7. Contraindication to the administration of osimertinib

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response (confirmed complete response [CR] or partial response [PR]) determined according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as per Independent Review Committee (IRC).

Secondary endpoints 7

1. Objective response (CR or PR) determined according to RECIST Version 1.1 as per IRC.
2. Occurrence of Adverse Events (AEs) and treatment related AEs. Occurrence of abnormalities (Grade ≥ 3) in laboratory test values (hematology and coagulation, biochemistry) and urinalysis. Occurrence of markedly abnormal vital sign measurements change in body weight, and Eastern Cooperative Oncology Group (ECOG) performance status. Occurrence of clinically significantly abnormal electrocardiograms (ECGs).
3. Occurrence of AEs and treatment related AEs. Occurrence of abnormalities (Grade ≥ 3) in laboratory test values (hematology and coagulation, biochemistry) and urinalysis. Occurrence of markedly abnormal vital sign measurements change in body weight, and ECOG performance status. Occurrence of clinically significantly abnormal ECGs.
4. Objective response according to RECIST v1.1 assessed by the investigator. Confirmed CR assessed by the IRC and by the investigator. Duration of response assessed from CR or PR until disease progression, death, or last tumor assessment assessed by IRB and investigator. Disease control (CR+PR or confirmed SD lasting at least 12 weeks) as assessed by the CRI and by the investigator. PFS according to RECIST v1.1 by IRC and by Investigator. Overall survival.
5. Patient reported outcomes/health related quality of life as reported using the following: EuroQol Five Dimension Five Level Scale. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30. NSCLC Symptom Assessment Questionnaire.
6. Single and multiple dose PK profile of osimertinib, tepotinib, and their metabolites including but not limited to AUC0-t, Cmax, and tmax after first dose (Day 1) and after multiple study intervention dose administrations (Day 15). Population PK profile of osimertinib, tepotinib, and their metabolites, including, but not limited to, CL/f and VZ/f based on sparse PK sampling on Day 1, Cycle 1 and 2 (all study participants).
7. Mutation status in EGFR and other pathways assessed in circulating tumor deoxyribonucleic acid (ctDNA) at Baseline and progression (all study participants).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Healthcare KGaA

Sponsor organisation

Merck Healthcare KGaA

Address

Gebaeude D11, 128 F, Frankfurter Strasse 250 128 F Frankfurter Strasse 250

City

Darmstadt

Postcode

64293

Country

Germany

Scientific contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Third parties 7

Locations

5 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications