Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC

EGFR-mutant Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase Ib, Open Label, Multi-center Study to Characterize the Safety, Tolerability and Preliminary Efficacy of EGF816 in Combination With Selected Targeted Agents in EGFR Mutant NSCLC

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03333343
• Other study ID #: CEGF816X2102
• Secondary ID: 2017-002496-25
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 29, 2018
• Est. completion date: December 16, 2024

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study purpose is to evaluate the safety, tolerability, and preliminary efficacy of the addition of INC280, trametinib, ribociclib, gefitinib, or LXH254 to EGF816 in adult patients with advanced EGFR-mutant NSCLC.

Description:

This is a Phase Ib, open label, non-randomized dose escalation study of EGF816 in combination with ribociclib, trametinib, or LXH254, followed by dose expansion of EGF816 in combination with ribociclib, trametinib, LXH254, INC280, or gefitinib in adult patients with advanced EGFR-mutant NSCLC. During the dose escalation part, patients will be assigned to the addition of trametinib, ribociclib, or LXH254 to EGF816. Following determination of the recommended dose for the combination of EGF816 + trametinib, EGF816 + ribociclib, and EGF816 + LXH254, patients may be enrolled to the dose expansion arms of each of these combinations. Patients may also be assigned to EGF816 + INC280 or EGF816 + gefitinib in dose expansion. Efficacy assessments will be performed at baseline and every 2 cycles during treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 105
• Est. completion date: December 16, 2024
• Est. primary completion date: December 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed locally advanced (stage IIIB) or metastatic (stage IV) EGFR mutant (ex19del, L858R) NSCLC.
• Requirements of EGFR mutation status and prior lines of treatment:
• Treatment naive patients, who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation (e.g., L858R and/or ex19del), have not received any systemic antineoplastic therapy for advanced NSCLC and are eligible to receive EGFR TKI treatment. Patients with EGFR exon 20 insertion/duplication are not eligible. Note: patients who have received only one cycle of chemotherapy in the advanced setting are allowed.
• Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation AND an acquired T790M mutation (e.g., L858R and/or ex19del, T790M+) following progression on prior treatment with a 1st-generation EGFR TKI or 2nd-generation EGFR TKI. These patients may not have received more than 4 prior lines of antineoplastic therapy in the advanced setting, including EGFR TKI, and may not have received any agent targeting EGFR T790M mutation (i.e., 3rd-generation EGFR TKI).
• Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation and a "de novo" T790M mutation (i.e., no prior treatment with any agent known to inhibit EGFR including EGFR TKI). These patients may not have received more than 3 prior lines of antineoplastic therapy in the advanced setting, and may not have received any prior 3rd generation EGFR TKI.
• Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy during therapy on this study, and at screening if an archival tumor sample obtained since the diagnosis of advanced disease (1L patients) or since last treatment failure (2L+ patients) is not available.

Exclusion Criteria:

• Patients with a history or presence of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
• Patients with unstable brain metastases.
• Patients with a history of another malignancy.
• Patients with a known history of human immunodeficiency virus (HIV) seropositivity.
• Patients with clinically significant, uncontrolled heart disease.
• Patients participating in additional parallel investigational drug or medical device studies.
• Prior therapies:
• Patients who have been treated with EGFR TKI in the adjuvant setting within 6 months, unless acquired EGFR T790M is present in a tumor or blood sample obtained since the discontinuation of the EGFR TKI.
• Patients who have been treated with prior EGFR TKI targeting T790M (3rd generation).
• Patients who have been treated with systemic anti-neoplastic therapy within:
• 2 weeks for fluoropyrimidine monotherapy
• 6 weeks for nitrosoureas and mitomycin
• 4 weeks or = 5 half-lives (whichever is shorter) for biological therapy (including monoclonal antibodies) and continuous or intermittent small molecule therapeutics or any other investigational agent

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• EGFR-mutant Non-small Cell Lung Cancer

Intervention

Drug:
• EGF816
Study Drug
• trametinib
Study Drug
• ribociclib
Study Drug
• LXH254
Study Drug
• INC280
Study Drug
• gefitinib
Study Drug

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Toronto	Ontario
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Koeln
Hong Kong	Novartis Investigative Site	Shatin New Territories
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Rozzano	MI
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Canada,  Germany,  Hong Kong,  Italy,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events and serious adverse events	Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.	Every day until study end, approximately 4 years
Primary	ORR2	Modified objective response rate (ORR2) per RECIST v1.1 (taking as baseline the most recent assessment prior to initiating combination)	Every 8-12 weeks until study ends, approximately 4 years
Secondary	ORR	Overall response rate (ORR) per RECIST v1.1	Every 8-12 weeks until study ends, approximately 4 years
Secondary	PFS	Time from the date of first dose of study treatment to the date of first documented disease progression (per RECIST v1.1) or death due to any cause	Every 8-12 weeks until study ends, approximately 4 years
Secondary	DCR	Proportion of patients with best overall response of CR, PR, or SD	Every 8-12 weeks until study ends, approximately 4 years
Secondary	DOR	Time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause	Every 8-12 weeks until study ends, approximately 4 years
Secondary	Time to response		Every 8-12 weeks until study ends, approximately 4 years