Glumetinib Combined With Osimertinib Treatment for Non-Small Cell Lung Cancer Patients

Shanghai JMT-Bio

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Recurrent or Metastatic NSCLC Patients With Classical EGFR Mutations Accompanied by MET Amplification or Overexpression

Treatments: Drug: Osimertinib Mesylate Tablets; Drug: Glumetinib Tablets; Drug: Glumetinib Tablets Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06908772

SYH2065-003

Details and patient eligibility

About

To evaluate the efficacy and safety of glumetinib combined with osimertinib as the first-line treatment for locally advanced or metastatic NSCLC.

Full description

In the Phase II stage, eligible subjects who have passed screening will be randomly assigned in a 1:1:1 ratio into the Group 1, Group 2, and Group 3 to receive study treatment:

In the Phase III stage, eligible subjects who have passed screening will be randomly assigned in a 1:1 ratio into the test group and the control group to receive the study treatments, and the RP3D obtained from Phase II will be used as the dose of glumetinib for the test group.

Randomization stratification factors include: c-MET status (≥2+, ≥75% and 3+, <50% vs 3+, ≥50% or FISH positive), and EGFR-sensitive mutation type (19Del vs L858R).

In both the Phase II and Phase III stages, each treatment cycle is every 3 weeks, with continuous treatment until progressive disease (PD) confirmed by the investigator, intolerable toxicity, withdrawal of informed consent by the subject, loss to follow-up, death, or other criteria for terminating treatment as specified in the protocol, whichever occurs first.

Enrollment: 390 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1. Able to understand and voluntarily sign the written informed consent form (ICF); 2. Male or female subjects aged 18 to 75 years (inclusive). 3. Patients with NSCLC who have unresectable locally advanced or metastatic disease; 4. At least one measurable lesion, as defined by RECIST 1.1 criteria; 5. ECOG performance status of 0 or 1; 6. Expected survival ≥ 3 months; 7. Adequate function of major organs and bone marrow; 8. Women or man of childbearing potential must use highly effective contraception.

Exclusion criteria

1. Prior treatment with an EGFR inhibitor or MET inhibitor;
2. Patients with metastases to meninges; with spinal cord compression; symptomatic and unstable brain metastasis;
3. Patients who have taken strong inducers or inhibitors of CYP3A4 within 2 weeks prior to the first dose of the study drug, or who cannot discontinue the use of strong CYP3A4 inducers and inhibitors during the study;
4. Patients with a history of autoimmune diseases, a history of immunodeficiency, including positive for HIV, or other acquired or congenital immunodeficiency diseases, or a history of organ transplant;
5. Presence of active infection (e.g., subjects are receiving anti-infection therapy);
6. Severe or uncontrolled cardiovascular disorder requiring treatment;
7. Refractory nausea, vomiting, chronic gastrointestinal disease, inability to swallow drugs orally;
8. Women who are pregnant or breastfeeding;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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390 participants in 3 patient groups

Glumetinib（200 mg） + Osimertinib

Experimental group

Description:

Group 1: Glumetinib 200 mg oral QD + Osimertinib 80 mg oral QD.

Treatment:

Drug: Glumetinib Tablets

Drug: Osimertinib Mesylate Tablets

Glumetinib（300mg） + Osimertinib

Experimental group

Description:

Group 2: Glumetinib 300 mg oral QD + Osimertinib 80 mg oral QD;

Treatment:

Drug: Glumetinib Tablets

Drug: Osimertinib Mesylate Tablets

Osimertinib

Experimental group

Description:

Group 3: Osimertinib 80 mg oral QD.

Treatment:

Drug: Glumetinib Tablets Placebo

Drug: Osimertinib Mesylate Tablets