Primary: To assess 6 month PFS rate of Nivolumab in combination with EGF816 in EGFR mutated NSCLC patients and of Nivolumab in combination with INC280 in patients with cMET positive NSCLC patientsSecondary: 1: To assess clinical activity of…
ID
Source
Brief title
Condition
- Breast neoplasms benign (incl nipple)
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free survival 6 months.
Secondary outcome
Other progression free survivals, overall response rate, disease control rate
and overall survival. Adverse events.
Background summary
Currently approved epidermal growth factor receptor tyrosine-kinase inhibitors
(EGFR TKI) are effective in activated EGFR mutant non-small cell lung cancer
(NSCLC), however nearly all patients develop resistance. cMET positive NSCLC
patients progressing on chemotherapy fair prognostically worse than their
non-cMET positive counterparts. Harnessing the immune system to treat patients
with NSCLC represents a novel and exciting new treatment approach. The
anti-PD-1 antibody Nivolumab has demonstrated response rates of up to 20% in
patients with NSCLC and has been safely combined with several small molecules
as well as chemotherapies.
In order to explore the hypothesis that concurrent treatment with an immune
checkpoint inhibitor along with a targeted therapy is safe and may result in
durable and sustained responses, Nivolumab will be combined with either the
third generation EGFR TKI, EGF816, in EGFR T790M NSCLC patients who have
developed resistance to EGFR TKI treatment or with the highly selective and
potent c-MET inhibitor, INC280, in cMET positive (EGFR wild type) patients who
progressed on chemotherapy.
Study objective
Primary: To assess 6 month PFS rate of Nivolumab in combination with EGF816 in
EGFR mutated NSCLC patients and of Nivolumab in combination with INC280 in
patients with cMET positive NSCLC patients
Secondary: 1: To assess clinical activity of Nivolumab in combination with
EGF816 and of Nivolumab in combination with INC280 as measured by other
progression free survivals, overall response rate, disease control rate and
overall survival. 2: To characterize the safety and tolerability of Nivolumab in
combination with EGF816 and of Nivolumab in combination with INC280.
Study design
Multicenter phase II open-label study, with a safety monitoring cohort.
Study treatments:
* Nivolumab IV infusion every 2 weeks (3 mg/kg) plus EGF816 capsules once daily
150 mg.
* Nivolumab IV infusion every 2 weeks (3 mg/kg) plus INC280 capsules twice
daily 400 mg.
Treatment until disease progression or unacceptable side effects. Patients who
discontinue study treatment for any reason other than disease progression will
be followed up for progression of disease and all patients will be followed for
survival.
Approx. 100 patients (50 per treatment group).
Safety monitoring cohorts of 6-12 patients per treatment group with more
intense monitoring.
Intervention
Treatment with nivolumab in combination with EGF816 or INC280.
Study burden and risks
Risk: Adverse effects of the combination of study drugs.
Burden: Cycles of 4 weeks. Cycle 1: 5 visits, cycle 2; 4 visits, from cycle 3
onwards: 2 visits. Duration mostly 1-4 hours. Some visits up to 8 hours.
2 infusions with nivolumab per cycle (approx. 200 ml).
Physical examination: cycle 1-2: 3 times, from cycle 3 onwards once/cycle.
Blood tests (5-40 ml/occasion): every visit.
Pulse oximetry: twice/cycle.
Pregnancy test: screening, once/cycle, 30 days after trial in blood. Up to 5
maanden after treatment in urine (possibly at home)
Tumor measurements: every 8 weeks for the 1st 12 cycles, every 12 weeks
thereafter.
ECG: cycle 1: twice, from cycle 2 onwards once/cycle.
Tumorbiopsie: once and once optional.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
* Female and male patients * 18 years of age.
* Advanced metastatic and/or unresectable NSCLC.
* Measurable disease.
* Group 1: confirmed T790M EGFR mutation.
* Group 2: confirmed c-MET positive.
* ECOG performance status 0, 1, 2.
Exclusion criteria
* Group 1: More than one prior line of EGFR TKI therapy.
* Group 2: Previous treatment with a c-MET inhibitor or HGFtargeting therapy.
* Prior treatment with PD1/PD-L1 targeting therapies.
* Patients who require emergent use of systemic steroids, emergent surgery and/or radiotherapy.
* Interstitial lung disease.
* Any active or history of autoimmune disease, hepatitis B virus or hepatitis C virus
* Prohibited co-medication: see protocol page 46.
* Pregnancy, lactation, inadequate contraception (males and females). See protocol page 30-31 for details.
* Group 2: GI impariment resulting in altered absorption of INC280
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR201400373120-NL |
| CCMO | NL51874.031.14 |