Description:
To determine the efficacy and safety of Nivolumab in combination with EGF816 and of Nivolumab
in combination with INC280 in previously treated NSCLC patients
Title
- Brief Title: Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer
- Official Title: A Phase II, Multicenter, Open-label Study of EGF816 in Combination With Nivolumab in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer and of INC280 in Combination With Nivolumab in Adult Patients With cMet Positive Non-small Cell Lung Cancer
Clinical Trial IDs
- ORG STUDY ID:
CEGF816X2201C
- SECONDARY ID:
2014-003731-20
- NCT ID:
NCT02323126
Conditions
- Non Small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
EGF816 | | Nivolumab and EGF816 |
INC280 | | Nivolumab and INC280 |
Nivolumab | | Nivolumab and EGF816 |
Purpose
To determine the efficacy and safety of Nivolumab in combination with EGF816 and of Nivolumab
in combination with INC280 in previously treated NSCLC patients
Detailed Description
This study has two arms:
Arm 1 (EGF816 + nivolumab) is currently closed to new enrollment.
Arm 2 (INC280 + nivolumab) is open and enrolling as planned.
Trial Arms
Name | Type | Description | Interventions |
---|
Nivolumab and EGF816 | Experimental | Arm 1 (EGF816 + nivolumab) is currently closed to new enrollment. | |
Nivolumab and INC280 | Experimental | Arm 2 (INC280 + nivolumab) is open and enrolling as planned. | |
Eligibility Criteria
Inclusion Criteria:
- Written informed consent must be obtained prior to any screening procedures
- Presence of at least one measurable lesion according to RECIST v.1.1
- ECOG performance status ≤ 2
- Patients with histologically documented locally advanced, recurrent and/or metastatic
NSCLC
- Tumor tissue for determination and/or confirmation of genetic pre-requisites (i.e.
EGFR T790M positivity post progression on EGFR TKI for Group 1; cMet status for Group
2) must be provided for analysis
Group 1 patients:
- Patients with EGFR T790M NSCLC (adenocarcinoma)
- Documented progression of disease according to RECIST v1.1 following primary standard
of care (e.g. erlotinib, gefitinib)
Group 2 patients:
- Patients with EGFR wild-type NSCLC
- Documented progression of disease according to RECIST v1.1 following standard of care
(e.g. platinum doublet).
Exclusion Criteria:
- Patients who have received more than one prior line of EGFR TKI therapy1 (applies only
to Group 1)
- Previous treatment with a c-MET inhibitor or HGF-targeting therapy (applies only to
Group 2)
- Patients with brain metastases. However, if radiation therapy and/or surgery has been
completed and serial evaluation by CT (with contrast enhancement) or MRI over a
minimum of one month demonstrates the disease to be stable and if the patient remains
must have no need for treatment with steroids
- Patients who require emergent use of systemic steroids, chronic use of prednisone
(greater than 10mg or an equivalent steroid dose daily) or emergent surgery and/or
radiotherapy.
- History of allergy or hypersensitivity to nivolumab components
- Patients with any known or suspected, current or past history of, autoimmune disease.
Patients with type I diabetes mellitus, hypothyroidism only requiring hormone
replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring
systemic treatment, or conditions not expected to recur in the absence of an external
trigger are permitted to enroll
- Patients with a condition requiring chronic systemic treatment with either
corticosteroids(> 10 mg daily prednisone equivalent) or other immunosuppressive
medications within 14 days of treatment start. Inhaled or topical steroids, and
adrenal replacement steroid doses> 10 mg daily prednisone equivalent, are permitted in
the absence of active autoimmune disease
- Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS)
- Any positive test for hepatitis B virus or hepatitis C virus indicating acute or
chronic infection
- Patients with interstitial lung disease that is symptomatic or may interfere with the
detection or management of suspected drug-related pulmonary toxicity
- Patients with interstitial lung disease that is symptomatic or may interfere with the
detection or management of suspected drug-related pulmonary toxicity
Prior therapy:
- Patients who have been treated with prior PD-1 and PD-L1 agents
- Patients who previously received agents targeting c-MET and/or EGFR T790M Note:
Previous treatment with afatinib may be allowable after discussions between Novartis
and Investigator.
- Patients with the following laboratory abnormalities:
- Absolute Neutrophil Count (ANC) <1.5 x 109/L
- Hemoglobin (Hgb) <9 g/dL
- Platelets <100 x 109/L
- Total bilirubin >1.5 x upper limit of normal (ULN). For patients with Gilbert's
syndrome total bilirubin >2.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN
- Serum creatinine >1.5 x ULN and/or measured or calculated creatinine clearance
<75% LLN
- For patients being screened for Group 2, asymptomatic serum amylase > CTCAE Grade
2 (1.5-2.0 x ULN). Patients with Grade 1 or Grade 2 serum amylase at the
beginning of the study must be confirmed to have no signs or symptoms suggesting
pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging
findings of pancreas, etc.)
- For patients being screened for Group 2: Serum lipase > ULN
- Female patients who are either pregnant or nursing.
- Women of child bearing potential who refuse or are not able to use a highly effective
method of contraception as defined in the study protocol.
- Sexually active males unless they use a condom during intercourse while taking drug
and for 31 weeks after the last dose of study treatment.
Other protocol-related inclusion/exclusion criteria may apply.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression Free Survival (PFS) Rate Using RECIST version1.1 |
Time Frame: | 6 month |
Safety Issue: | |
Description: | Analysis of PFS by group using Kaplan-Meier method. results given as Kaplan Meier estimates (%) PFS rate |
Secondary Outcome Measures
Measure: | Number of Participants With Adverse Events (AEs) |
Time Frame: | Continuously during study until 100 days after post study treatment |
Safety Issue: | |
Description: | Safety of EGF816 and Nivolumab and INC280 and Nivolumab by looking at hematology and chemistry laboratory parameters, vital signs, and electrocardiograms (ECGs) |
Measure: | Objective Response Rate (ORR) |
Time Frame: | baseline, every 8 weeks up to cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Disease Control Rate |
Time Frame: | baseline, every 8 weeks upto cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Progression Free Survival |
Time Frame: | baseline, every 8 weeks upto cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Overall Survival |
Time Frame: | Start of treatment until death, average 1 year |
Safety Issue: | |
Description: | |
Measure: | Plasma Pharmacokinetic Parameters (AUClast, AUC0-t,AUCtau,Cmax, Tmax) |
Time Frame: | Cycle 1: Day1, Day 8, Day 15 and Cycle 2: Day 1, Cycle 4: Day 1 Cycle 6: Day 1 and Cycle 8: Day 1 Subsequent cycles (nivolumab only): every 8th cycle until discontinuation of study treatment |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Non small cell lung cancer,
- NSCLC,
- EGFR-mutated,
- EGF816,
- INC280,
- Nivolumab,
- EGFR-T790M NSCLC,
- EGFR wild-type (wt),
- cMET positive NSCLC,
- cMET negative NSCLC
Last Updated
June 15, 2021