A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

NCT ID: NCT02108964

Last Updated: 2024-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-06
• Study Completion Date: 2023-08-15

Brief Summary

This is a Phase I/II, multi-center, open-label study, composed with a Phase I part (dose-escalation phase) followed by a Phase II part (expansion phase).

The dose escalation phase was designed to determine as primary objective the maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) of EGF816 monotherapy in adult subjects with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC harboring specific EGFR mutations. Patients may have or not have received prior lines of antineoplastic therapy. An adaptive Bayesian Logistic Regression Model (BLRM) employing the escalation with overdose control (EWOC) principle will be used during the dose escalation part for dose level selection and MTD recommendation. The primary objective of the Phase II part is to estimate antitumor activity of EGF816 as measured by overall response rate (ORR) determined by Blinded Independent Review Committee (BIRC) assessment in accordance to RECIST 1.1.

Detailed Description

Following completion of screening procedures and confirmation of patient eligibility, the participants are enrolled in the study. The study treatment begin on Cycle 1, Day 1 with the first administration of EGF816. A treatment cycle is defined as 28 days. Oral EGF816 is administered once daily on a continuous schedule until patient experiences unacceptable toxicity, progressive disease (PD), and/or treatment is discontinued at the discretion of the investigator, patient withdrawal of consent, or due to any other reasons. Treatment with EGF816 may be continued beyond RECIST 1.1 defined PD, if, in the judgment of the investigator, there is evidence of clinical benefit and the patient wishes to continue with the study treatment.

Conditions

Advanced Non-small Cell Lung Cancer

Keywords

NSCLC; Non-small Cell Lung Cancer EGFRmut; EGFR TKIs (EGF816); acquired T790M mutation; de novo T790M mutation; EGFR TKI activating mutation (i.e. L858R or ex19del); Treatment naive advanced NSCLC with EGFR activating mutations; Locally advanced NSCLC (Stage IIIB NSCLC not amenable to definitive multi-modality therapy including surgery); Metastatic NSCLC refers to Stage IV NSCLC; 1st line

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I part

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations will be administered escalated doses of EGF816 orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study. The starting dose for the Phase I part first cohort of patients will be 75 mg once per day capsule.

Group Type: EXPERIMENTAL

EGF816

Intervention Type: DRUG

EGF816 will be dosed once daily. On the first day of each treatment cycle, the patient receives an adequate drug supply for self-administration at home. The investigator will instruct the patient to take EGF816 exactly as prescribed.

Phase II part

Treatment naïve participants with locally advanced or metastatic NSCLC harboring EGFR mutations will be administered with EGF816 at RP2D during Phase II part of the study.

Group Type: EXPERIMENTAL

EGF816

Intervention Type: DRUG

EGF816 will be dosed once daily. On the first day of each treatment cycle, the patient receives an adequate drug supply for self-administration at home. The investigator will instruct the patient to take EGF816 exactly as prescribed.

Interventions

EGF816

EGF816 will be dosed once daily. On the first day of each treatment cycle, the patient receives an adequate drug supply for self-administration at home. The investigator will instruct the patient to take EGF816 exactly as prescribed.

Intervention Type: DRUG

Other Intervention Names

Nazartinib

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed locally advanced (stage IIIB not amenable to definitive multi-modality therapy including surgery) or metastatic (stage IV) EGFR mutant NSCLC.
• Patients with controlled brain metastases
• ECOG performance status: Phase I part: 0, 1, or 2; Phase II part: 0 or 1
• Presence of at least one measurable lesion according to RECIST 1.1 per investigator assessment
• Patients who are either Hepatitis B surface antigen (HBsAg) positive or hepatitis B virus (HBV)-DNA positive must be willing and able to take antiviral therapy 1-2 weeks prior to 1st dose of EGF816 treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816
• Patients must have negative hepatitis C antibody (HCV-Ab) or positive HCV-Ab but undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study.
• For Phase I: patients must have failed no more than 3 lines of any systemic antineoplastic therapy for advanced NSCLC, including EGFR-TKI
• For Phase II: patients must be naïve from any systemic antineoplastic therapy in the advanced setting. Patients who have failed no more than 1 cycle of systemic antineoplastic therapy in the advanced setting are allowed.

Exclusion Criteria

• Patients with a history or presence of interstitial lung disease (ILD) or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention)
• Presence or history of another malignancy
• Undergone a bone marrow or solid organ transplant
• Known history of human immunodeficiency virus (HIV) seropositivity
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except for control of brain metastases, topical applications, inhaled sprays, eye drops or local injections
• Patients with clinically significant, uncontrolled heart disease
• Any prior therapies ≤ 4 weeks prior to the first dose of study treatment
• Patients who are receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 and cannot be discontinued 1 week prior to the start of EGF816 treatment and for the duration of the study.
• Patients who have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of EGF816
• Patients who are receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of study treatment, and for the duration of the study
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception
• Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after stopping treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Massachusetts General Hospital Mass General

Boston, Massachusetts, United States

Memorial Sloan Kettering Oncology Department

New York, New York, United States

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Zoetermeer, , Netherlands

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Taipei, , Taiwan

Countries

Belgium; China; France; Italy; United States; Canada; Germany; Japan; Netherlands; Singapore; South Korea; Spain; Taiwan

References

Tan DSW, Kim SW, Ponce Aix S, Sequist LV, Smit EF, Yang JCH, Hida T, Toyozawa R, Felip E, Wolf J, Grohe C, Leighl NB, Riely G, Cui X, Zou M, Ghebremariam S, O'Sullivan-Djentuh L, Belli R, Giovannini M, Kim DW. Nazartinib for treatment-naive EGFR-mutant non-small cell lung cancer: Results of a phase 2, single-arm, open-label study. Eur J Cancer. 2022 Sep;172:276-286. doi: 10.1016/j.ejca.2022.05.023. Epub 2022 Jul 7.

Reference Type: DERIVED

PMID: 35810553 (View on PubMed)

Tan DS, Leighl NB, Riely GJ, Yang JC, Sequist LV, Wolf J, Seto T, Felip E, Aix SP, Jonnaert M, Pan C, Tan EY, Ko J, Moody SE, Kim DW. Safety and efficacy of nazartinib (EGF816) in adults with EGFR-mutant non-small-cell lung carcinoma: a multicentre, open-label, phase 1 study. Lancet Respir Med. 2020 Jun;8(6):561-572. doi: 10.1016/S2213-2600(19)30267-X. Epub 2020 Jan 15.

Reference Type: DERIVED

PMID: 31954624 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-004482-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CEGF816X2101

Identifier Type: -

Identifier Source: org_study_id