Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (Geometry Mono-1)

• Status: Active, not recruiting
• Trial end date: 2023-03-23
• Target enrollment: 0
• Participant gender: All

Summary

A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) as measured by overall response rate (ORR). The study will also evaluate safety and pharmacokinetics of INC280.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals

Criteria

Inclusion Criteria:

• Stage IIIB or IV NSCLC (any histology) at the time of study entry

• Histologically or cytologically confirmed diagnosis of NSCLC that is:

1. EGFR wt as per patient standard of care by a validated test

2. AND ALK-negative rearrangement as part of the patient standard of care by a validated test

3. AND (by central assessment) either:

• Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or

• Cohort 2: Pre-treated patients with cMET GCN ≥4 and < 6, or

• Cohort 3: Pre-treated patients with cMET GCN < 4, or

• Cohort 4: Pre-treated patients with cMET mutations regardless of cMET GCN, or

• Cohort 5: Treatment-naïve patients with cMET dysregulation, or

• Cohort 6: Pre-treated patients with either cMET GCN ≥ 10 without cMET mutations or cMET mutations regardless of cMET GCN, or

• Cohort 7: Treatment-naïve patients with cMET mutations regardless of cMET GCN

• To be eligible for Cohorts 1-4, patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease

• To be eligible for Cohort 6, patients must have failed one prior line of systemic therapy for advanced/metastatic disease

• To be eligible for Cohort 5 and Cohort 7, patients must not have received any systemic therapy for advanced/metastatic disease

• At least one measurable lesion as defined by RECIST 1.1

• Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.

• Patients must have adequate organ function

• ECOG performance status (PS) of 0 or 1 Details and other protocol-defined inclusion criteria may apply

Exclusion Criteria:

• Prior treatment with crizotinib, or any other cMET or HGF inhibitor

• Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations

• Patients with characterized ALK-positive rearrangement

• Clinically significant, uncontrolled heart diseases.

• Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study:

• Strong inducers of CYP3A4

• Impairment of GI function or GI disease that may significantly alter the absorption of INC280

• Patients receiving treatment with any enzyme-inducing anticonvulsant

• Applicable to Cohorts 1-4 and Cohort 6 only: Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose

• Pregnant or nursing women

• Women of child-bearing potential, unless they are using highly effective methods of contraception

• Sexually active males unless they use a condom during intercourse

• Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis

Other protocol-defined exclusion criteria may apply