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 (EGF816)

• ClinicalTrials.gov Identifier: NCT02323126
• Recruitment Status: Active, not recruiting
• First Posted: December 23, 2014
• Last Update Posted: February 24, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: December 18, 2014
• First Posted Date: December 23, 2014
• Last Update Posted Date: February 24, 2021
• Actual Study Start Date: February 9, 2015
• Estimated Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 18, 2014): Progression Free Survival (PFS) rate using RECIST version1.1 [ Time Frame: 6 month ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 18, 2014)

• Number of participants with Adverse Events (AEs) [ Time Frame: Continuously during study until 100 days after post study treatment ]
  Safety of EGF816 and Nivolumab and INC280 and Nivolumab by looking at hematology and chemistry laboratory parameters, vital signs, and electrocardiograms (ECGs)
• 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 ]
• 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 ]
• 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 ]
• Overall Survival [ Time Frame: Start of treatment until death, average 1 year ]
• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer

Intervention

• Drug: EGF816
• Drug: INC280
• Drug: Nivolumab

Study Arms

• Experimental: Nivolumab and EGF816
  Arm 1 (EGF816 + nivolumab) is currently closed to new enrollment.
  Interventions:

  • Drug: EGF816
  • Drug: Nivolumab
• Experimental: Nivolumab and INC280
  Arm 2 (INC280 + nivolumab) is open and enrolling as planned.
  Interventions:

  • Drug: INC280
  • Drug: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 8, 2020): 64
• Original Estimated Enrollment (submitted: December 18, 2014): 100
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Italy, Netherlands, Singapore, Spain, Switzerland, United States
• Removed Location Countries: Canada, Norway

Administrative Information

• NCT Number: NCT02323126
• Other Study ID Numbers: CEGF816X2201C; 2014-003731-20 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Study Sponsor: Novartis Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: February 2021