A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment

Novartis

Status and phase: Completed; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: INC280; Drug: Gefitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01610336

2011-002569-39 (EudraCT Number)

CINC280X2202

Details and patient eligibility

About

This study assessed the safety and efficacy of escalating doses INC280 when added to gefitinib in patients with lung cancer that were known to have dysregulation of the c-MET pathway and who had failed after benefiting on a prior treatment with either gefitinib or erlotinib.

Full description

The Phase Ib dose escalation part was aimed at the determination of the MTD/RP2D of capmatinib in combination with 250 mg gefitinib in patients with NSCLC patients with epidermal growth factor receptor (EGFR) mutation and cMET dysregulation and showing disease progression following EGFR tyrosine-kinase inhibitor (EGFR TKI) therapy. Dose escalation started with a dose of 100 mg/day to a maximum of 1200 mg/day, as capsule or tablet formulation. Successive cohorts of patients were to receive increasing doses of capmatinib in combination with a 250 mg once daily (qd) dose of gefitinib until the MTD/RP2D of capmatinib had been determined. The Phase II dose expansion part consisted of 400 mg capmatinib twice daily (bid), as either capsules or tablets, in combination with 250 mg gefitinib.

Enrollment: 161 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented EGFR mutation

• Documented c-MET dysregulation

• Prior clinical benefit on EGFR inhibitors and then subsequent progression

  -≥ 18 year old

• Life expectancy of ≥ 3 months

• ECOG performance status ≤ 2

Exclusion criteria

• Unable to swallow tables once or twice daily
• Previous treatment with c-MET inhibitor
• Any unresolved toxicity from previous anticancer therapy greater than grade 1
• History of cystic fibrosis
• History of acute or chronic pancreatitis
• Unable to undergo MRI or CT scans
• Known history of HIV
• Undergone a bone marrow or solid organ transplant
• Clinically significant wound or lung tumor lesions with increased likelihood of bleeding
• Pregnant or nursing

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

161 participants in 11 patient groups

INC280 100 mg Cap QD Phase Ib

Experimental group

Description:

cap=capsule; QD=once daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 200 mg Cap QD Phase Ib

Experimental group

Description:

cap=capsule; QD=once daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 400 mg Cap QD Phase Ib

Experimental group

Description:

cap=capsule; QD=once daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 800 mg Cap QD Phase Ib

Experimental group

Description:

cap=capsule; QD=once daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 200 mg Cap BID Phase Ib

Experimental group

Description:

cap=capsule; BID=twice daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 400 mg Cap BID Phase Ib

Experimental group

Description:

cap=capsule; BID=twice daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 600 mg Cap BID Phase Ib

Experimental group

Description:

cap=capsule; BID=twice daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 200 mg Tab BID Phase Ib

Experimental group

Description:

tab=tablet; BID=twice daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 400 mg Tab BID Phase Ib

Experimental group

Description:

tab=tablet; BID=twice daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 400 mg Cap BID Phase II

Experimental group

Description:

cap=capsule; BID=twice daily

Treatment:

Drug: Gefitinib

Drug: INC280

INC280 400 mg Tab BID Phase II

Experimental group

Description:

tab=tablet; BID=twice daily

Treatment:

Drug: Gefitinib

Drug: INC280