Description:
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.
Title
- Brief Title: A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment
- Official Title: A Phase IB/II, Open Label, Multicenter Study of INC280 Administered Orally in Combination With Gefitinib in Adult Patients With EGFR Mutated, c-MET-amplified Non-small Cell Lung Cancer Who Have Progressed After EGFR Inhibitor Treatment
Clinical Trial IDs
- ORG STUDY ID:
CINC280X2202
- SECONDARY ID:
2011-002569-39
- NCT ID:
NCT01610336
Conditions
- Non-small Cell Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| INC280 | Capmatinib | INC280 100 mg Cap QD Phase Ib |
| Gefitinib | | INC280 100 mg Cap QD Phase Ib |
Purpose
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.
Detailed 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| INC280 100 mg Cap QD Phase Ib | Experimental | cap=capsule; QD=once daily | |
| INC280 200 mg Cap QD Phase Ib | Experimental | cap=capsule; QD=once daily | |
| INC280 400 mg Cap QD Phase Ib | Experimental | cap=capsule; QD=once daily | |
| INC280 800 mg Cap QD Phase Ib | Experimental | cap=capsule; QD=once daily | |
| INC280 200 mg Cap BID Phase Ib | Experimental | cap=capsule; BID=twice daily | |
| INC280 400 mg Cap BID Phase Ib | Experimental | cap=capsule; BID=twice daily | |
| INC280 600 mg Cap BID Phase Ib | Experimental | cap=capsule; BID=twice daily | |
| INC280 200 mg Tab BID Phase Ib | Experimental | tab=tablet; BID=twice daily | |
| INC280 400 mg Tab BID Phase Ib | Experimental | tab=tablet; BID=twice daily | |
| INC280 400 mg Cap BID Phase II | Experimental | cap=capsule; BID=twice daily | |
| INC280 400 mg Tab BID Phase II | Experimental | tab=tablet; BID=twice daily | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase Ib: Frequency of Dose Limiting Toxicities (DLTs) |
| Time Frame: | Up to 215 weeks |
| Safety Issue: | |
| Description: | A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol. |
Secondary Outcome Measures
| Measure: | Phase Ib and II: Number of Participants With Adverse Events (AEs) |
| Time Frame: | Up to 421 weeks |
| Safety Issue: | |
| Description: | Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Measure: | Phase Ib and II: Number of Participants With Serious Adverse Events (SAEs) |
| Time Frame: | Up to 421 weeks |
| Safety Issue: | |
| Description: | Serious adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Measure: | Phase Ib and II: Number of Patients With Dose Reductions of INC280 by Dose Level |
| Time Frame: | Up to 417 weeks |
| Safety Issue: | |
| Description: | Number of patients with dose reductions of INC280 by dose level as a measure of tolerability. |
| Measure: | Phase Ib and II: Number of Patients With Dose Interruptions of Gefitinib by Dose Level |
| Time Frame: | Up to 417 weeks |
| Safety Issue: | |
| Description: | Number of patients with dose interruptions of gefitinib by dose level as a measure of tolerability |
| Measure: | Phase II: Overall Survival (OS) |
| Time Frame: | From date of treatment until death due to any cause, up to 70.2 months |
| Safety Issue: | |
| Description: | Overall survival is defined as the time from the start of treatment date to the date of death, due to any cause |
| Measure: | Phase II: Progression Free Survival (PFS) |
| Time Frame: | Up to 60.8 months |
| Safety Issue: | |
| Description: | Progression-free survivalis the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. |
| Measure: | Phase II: Duration of Response (DoR) |
| Time Frame: | Up to 23.2 months |
| Safety Issue: | |
| Description: | Duration of overall response (DOR) is defined as the time between the date of first documented response (CR or PR) and the date of first documented disease progression or death due to underlying cancer. |
| Measure: | Phase I: PK Parameters AUCtau of INC280 and Gefitinib |
| Time Frame: | Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days) |
| Safety Issue: | |
| Description: | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis.
Area under the plasma concentration-time curve (AUC) from time zero to the end of dosing interval at steady state (tau), where tau=24 hours for once daily dosing and tau=12 hours for twice daily dosing |
| Measure: | Phase I: PK Parameters Cmax of INC280 and Gefitinib |
| Time Frame: | Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days) |
| Safety Issue: | |
| Description: | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis.
Cmax is the maximum observed plasma concentration of INC280 and gefitinib |
| Measure: | Phase I: PK Parameters Tmax of INC280 and Gefitinib |
| Time Frame: | Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days) |
| Safety Issue: | |
| Description: | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis.
Tmax is the time to reach maximum plasma concentration of INC280 and gefitinib |
| Measure: | Phase I: PK Parameters Apparent Systemic Plasma Clearance Rate of INC280 and Gefitinib |
| Time Frame: | Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days) |
| Safety Issue: | |
| Description: | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis.
Apparent systemic plasma clearance rate of INC280 and gefitinib |
| Measure: | Phase I: PK Parameters Half-life of INC280 and Gefitinib |
| Time Frame: | Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose)(Cycle=28 days) |
| Safety Issue: | |
| Description: | PK parameters were estimated from each individual plasma concentration-time profile using non-compartmental analysis.
The elimination half-life of INC280 and gefitinib associated with the terminal slope (Lamda_z) of a semi-logarithmic plasma concentration-time curve |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- EGFR
- c-MET
- Lung cancer
- Gefitinib
- Erlotinib
- Non-small cell lung cancer (NSCLC)
- lung adenocarcinoma
- large-cell lung carcinoma
Last Updated
April 8, 2021
