Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nazartinib

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.

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.

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.

EGF816

Novartis Pharmaceuticals

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.

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.

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

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

Number of participants with DLTs during the first 28 days of therapy. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with EGF816 and meets any of the criteria described in the protocol. A participant with multiple occurrences of DLTs under one treatment is counted only once.

ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) determined by BIRC assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1

DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1

To characterize the PK properties of EGF816 and metabolite LMI258, Cmax will be calculated (Phase I \& II parts)

To characterize the PK properties of EGF816 and metabolite LMI258, Tmax will be calculated (Phase I \& II parts)

To characterize the PK properties of EGF816 and metabolite LMI258, AUCtau will be calculated (Phase I \& II parts)

Changes in EGFR signaling pathway of newly obtained tumor samples following EGF816 treatment will be evaluated by IHC of three pharmacodynamics (PD) biomarkers: p-EGFR, p-AKT and p-ERK. The assigned H-score semi-quantitatively assesses the expression level of these protein markers and their phosphorylated forms.

ORR is defined as proportion of patients with best overall response of PR+CR determined by Investigator assessment in accordance to RECIST 1.1

DCR is defined as the proportion of patients with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1

TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1

Assessment of the tolerability of EGF816 will be performed continuously during the treatment phase

DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by BIRC in accordance to RECIST 1.1

DCR is defined as the proportion of patients with best overall response of CR, PR, or SD determined by BIRC in accordance to RECIST 1.1

PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by BIRC in accordance to RECIST 1.1

TTR is defined as as the time from the date of first dose of study treatment to the date of first documented response (CR or PR) determined by by BIRC in accordance to RECIST 1.1

OS is defined as the time from first dose of the study treatment to the date of death due to any cause.

Any sign or symptom that occurs during the study treatment plus the 30 days post treatment

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 75 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 75 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 100 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 100 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 150 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 150 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 200 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 200 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 225 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 225 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 300 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 300 mg (Phase I Part)

Participants with locally advanced or metastatic NSCLC harboring specific EGFR mutations were administered with EGF816 350 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase I part of the study.

EGF816 350 mg (Phase I Part)

Treatment naïve participants with locally advanced or metastatic NSCLC harboring EGFR mutations were administered with 150 mg orally once a day as continuous daily dosing in each cycle (of 28 days) during Phase II part of the study.

EGF816 150 mg (Phase II Part)

All Subjects

Total

Age, Categorical

Sex: Female, Male

Race/Ethnicity, Customized

Study Director

Dose-determining set (DDS) including all patients who received at least one dose of EGF816 in the dose escalation phase who had met the minimum safety evaluation requirements (observed for ≥ 28 days following the first dose) and the minimum exposure criterion (at least 75% of the planned doses of EGF816) or discontinue earlier due to DLTs

Number of Participants With Dose Limiting Toxicities (DLTs) (Phase I Part)

Full Analysis Set (FAS) including participants who received at least one dose of EGF816

Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) (Phase II Part)

Progression-free Survival (PFS) by Investigator Assessment (Phase I & Phase II Parts)

Duration of Response (DOR) by Investigator Assessment (Phase I & II Parts)

Observed Maximum Plasma Concentration (Cmax) of EGF816 and Metabolite LMI258 (Phase I & Phase II Part)

Time to Maximum Plasma Concentration (Tmax) of EGF816 and Metabolite LMI258 (Phase I & Phase II Part)

Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) of EGF816 and Metabolite LMI258 (Phase I & Phase II Part)

Spots Global Cancer Trial Database for treatment naive advanced nsclc with egfr activating mutations