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

NCT02323126 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CEGF816X2201C2014-003731-20
• Study Type: interventional
• Target: 64
• Locations: 8 countries
• Sites: 13

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

Conditions

Non Small Cell Lung Cancer

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

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1

  PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PFS was modeled using a Weibull distribution and the PFS rate at 6 months was estimated from the posterior distribution.

  6 months

Secondary Outcomes (18)

• Overall Response Rate (ORR) Per RECIST v1.1

  From start of treatment until end of treatment, assessed up to 4.7 years

• Disease Control Rate (DCR) Per RECIST v1.1

  From start of treatment until end of treatment, assessed up to 4.7 years

• Median Progression-Free Survival (PFS) Per RECIST v1.1

  From start of treatment to first documented progression or death, assessed up to 5 years

• Progression-Free Survival (PFS) Rate at 3 Months Per RECIST v1.1

  3 months

• Overall Survival (OS) at 1 Year

  1 year

Study Arms (3)

Nivolumab and EGF816

EXPERIMENTAL

Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W

Drug: EGF816; Drug: Nivolumab

Nivolumab and INC280, high cMet

EXPERIMENTAL

Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W

Drug: INC280; Drug: Nivolumab

Nivolumab and INC280, low cMet

EXPERIMENTAL

Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W

Drug: INC280; Drug: Nivolumab

Interventions

EGF816 DRUG

EGF816 150 mg once daily (QD) administered orally as a capsule

Nivolumab and EGF816

INC280 DRUG

INC280 400 mg twice daily (BID) administered orally as a tablet

Nivolumab and INC280, high cMet; Nivolumab and INC280, low cMet

Nivolumab DRUG

Nivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion

Nivolumab and EGF816; Nivolumab and INC280, high cMet; Nivolumab and INC280, low cMet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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 asymptomatic without the 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 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

University of Texas MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Camperdown, New South Wales, 2050, Australia

Location

Novartis Investigative Site

Chermside, Queensland, 4032, Australia

Location

Novartis Investigative Site

La Tronche, 38700, France

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Perugia, PG, 06129, Italy

Location

Novartis Investigative Site

Aviano, PN, 33081, Italy

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Alicante, Valencia, 03010, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Chur, 7000, Switzerland

Location

Related Publications (1)

• Felip E, Metro G, Tan DSW, Wolf J, Mark M, Boyer M, Hughes BGM, Bearz A, Moro-Sibilot D, Le X, Puente J, Massuti B, Tiedt R, Wang Y, Xu C, Mardjuadi FI, Cobo M. Capmatinib plus nivolumab in pretreated patients with EGFR wild-type advanced non-small cell lung cancer. Lung Cancer. 2024 Jun;192:107820. doi: 10.1016/j.lungcan.2024.107820. Epub 2024 May 10.

  PMID: 38763104 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

nazartinib; capmatinib; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 23, 2014
• Study Start: February 9, 2015
• Primary Completion: September 23, 2019
• Study Completion: February 5, 2021
• Last Updated: February 28, 2022
• Results First Posted: June 15, 2021

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); DE (1); SG (1); CH (1); AU (2); FR (1); ES (4); US (1)