A Study of NX-019 in Patients With Advanced, Epidermal Growth Factor Receptor (EGFR) Mutant Cancer

EGFR Mutation-Related Tumors Clinical Trial

Official title:

A First-in-Human, Open-Label, Dose Escalation and Expansion Study of Orally Administered NX-019 in Patients With Advanced, EGFR Mutant Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05514496
• Other study ID #: NT019-101
• Status: Recruiting
• Phase: Phase 1
• Start date: October 5, 2022
• Est. completion date: October 17, 2027

Study information

• Verified date: March 2024
• Source: Nalo Therapeutics Inc.
• Contact: Nalo Therapeutics
• Phone: 323-909-6498
• Email: Info[@]nalotherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 2-part, first-in-human, open-label study to determine the safety and tolerability of NX-019 and preliminary efficacy in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutant cancer.

Description:

Part 1: The primary objective of Part 1 of this study is to evaluate the safety and tolerability of NX-019 and to determine the maximum tolerated dose (MTD)/Recommended Expansion Dose(s) (REDs).

Part 2: The primary objective of Part 2 of this study is to confirm the safety and tolerability of NX-019 at the REDs and, for each expansion cohort, the preliminary evidence of efficacy as measured by objective response rate (ORR).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 258
• Est. completion date: October 17, 2027
• Est. primary completion date: February 17, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed, locally advanced, or metastatic EGFR-mutant cancer and has progressed on or are intolerant to all standard therapy.

• Patients with non-small cell lung cancer (NSCLC) harboring a mutation that is sensitive to osimertinib must have received osimertinib prior to enrollment.

• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (evaluable disease acceptable for dose escalation part of study).

• =18 years of age (or age of consent in in accordance with local law).

• Life expectancy =3 months.

• Adequate organ and bone marrow function.

• All patients will have a baseline magnetic resonance imaging (MRI) of the brain.

• Resolution of any clinically significant toxic effects of prior therapy to Grade 0 or 1 according to the National Cancer Institute CTCAE v5.0 (exception of alopecia and Grade 2 peripheral neuropathy).

• Eastern Cooperative Oncology Group (ECOG) performance status of =2.

• Willingness of men and women of reproductive potential to observe conventional and effective birth control methods with failure rates of <1% for the duration of treatment and for 6 months following the last dose of study treatment.

• A negative serum pregnancy test at Screening and a negative (serum or urine) pregnancy test within 72 hours before the first dose of study drug (female patients of childbearing potential only).

• Willing and able to give informed consent and comply with protocol requirements for the duration of the study.

Specific Inclusion Criteria for Expansion Cohorts:

To be eligible during the expansion part of the study, patients must meet the above inclusion criteria, and the criteria for 1 of the following cohorts:

Expansion Cohort 1:

• Patients with NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who have progressed on or after prior EGFR TKI therapy.

Expansion Cohort 2:

• Patients with NSCLC with EGFR ex20ins mutations, who are not suitable for, or are unwilling to receive available ex20ins mutation targeted therapy.

Expansion Cohort 3:

• Patients with NSCLC with EGFR mutations for which there is no current targeted therapy, (i.e., exclusion of exon 19, exon 21 L858R, and ex20ins mutation).

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from participation in the study:

• Known C797X EGFR mutations or 1 or more known secondary drivers of disease.

• Disease requiring immediate palliative treatment with surgery or radiation therapy.

• Requirement for greater than 4 mg/day of dexamethasone (or equivalent) for management of CNS metastases.

• Received systemic anticancer chemotherapy, targeted agents, antibody therapy for cancer, immunotherapy for cancer, hormonal therapy or an investigational agent within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study drug treatment.

• Major surgery within 3 weeks prior to start of study drug treatment.

• Radiation therapy within 4 weeks prior to start of study drug treatment.

• Severe or unstable cardiac conditions within 6 months prior to starting study drug treatment.

• Severe or unstable medical condition including uncontrolled diabetes or unstable psychiatric condition.

• Dependent on contact lenses (unable to wear eyeglasses) and unable to comply with ophthalmic guidance.

• History of interstitial lung disease, radiation pneumonitis which required systemic steroid therapy, or other significant lung disease.

• Another active malignancy within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered cured, and, in the opinion of the Investigator, present a low risk of recurrence.

• Active infection requiring systemic therapy.

• Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) (i.e., hepatitis B surface antigen-positive), or hepatitis C virus (HCV) (i.e., detectable HCV ribonucleic acid [RNA]).

• Active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or conditions that may impact drug absorption.

• Pregnant or breastfeeding.

• Is using a strong CYP3A inhibitor or inducer, and cannot refrain from use from 7 days prior to the first dose and throughout the study.

• Is using a proton pump inhibitor and cannot refrain from use from 7 days prior to the first dose and throughout the study.

• Is using a sensitive substrate of P-gp with a narrow therapeutic window (e.g. digoxin).

• Any other condition, including significant skin or nail disease, that in the opinion of the Investigator would place the patient at an unacceptable risk or cause the patient to be unlikely to fully participate or comply with study procedures.

Related Conditions & MeSH terms

• EGFR Mutation-Related Tumors

Intervention

Drug:
• NX-019
NX-019 will be administered orally.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Taiwan	National Taiwan University Cancer Center	Taipei City	Taipei
United States	City of Hope Comprehensive Cancer Center - Duarte	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	City of Hope - Huntington Beach	Huntington Beach	California
United States	City of Hope Orange County Lennar Foundation Cancer Center	Irvine	California

Sponsors (1)

Lead Sponsor	Collaborator
Nalo Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 and Part 2: Incidence of Treatment-emergent Adverse Events (TEAEs)		Up to 4.5 years
Primary	Part 1 and Part 2: Incidence of Adverse Events of Special Interest (AESIs)		Up to 4.5 years
Primary	Part 1 and Part 2: Incidence of Serious Adverse Events (SAEs)		Up to 4.5 years
Primary	Part 2: Objective Response Rate		Up to 4.5 years
Secondary	Part 1: Progression-free Survival (PFS)		Up to 4.5 years
Secondary	Part 1: Objective Response Rate of NX-019		Up to 4.5 years
Secondary	Part 1 and Part 2: Plasma Concentration of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Cerebrospinal Fluid (CSF) Concentration of NX-019		Up to 43 days
Secondary	Part 1 and Part 2: Maximum Observed Serum Concentration (Cmax) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Area Under the Concentration Versus Time Curve (AUC) Over a Dosing interval (AUCtau) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: AUC from Time 0 to the Time of Last Quantifiable Plasma Concentration (AUC0-t) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: AUC from Time 0 to Infinity (AUC0-inf) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Percent of AUC Extrapolated (AUC%extrap) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Terminal Phase Elimination Half-life (t½) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Terminal Phase Elimination Rate Constant (?z) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Apparent Plasma Clearance (CL/F) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Apparent Volume of Distribution (Vd/F) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Accumulation Index Using Cmax (AICmax) and Accumulation Index Using AUC (AIAUC0-inf) of NX-019		Day 1, 2, and 15 of Cycle 1, Day 1 and 15 of Cycle 2, Day 1 of Cycle 3 and every odd-numbered Cycle thereafter (1 Cycle is 28 days)
Secondary	Part 1 and Part 2: Time to Response (TTR)		Up to 4.5 years
Secondary	Part 1 and Part 2: Duration of Response (DOR)		Up to 4.5 years
Secondary	Part 1 and Part 2: Disease Control Rate (DCR)		Up to 4.5 years
Secondary	Part 1 and Part 2: Overall Survival (OS)		Up to 4.5 years
Secondary	Part 1 and Part 2: Objective Response Rate for CNS (central nervous system) Metastases		Up to 4.5 years
Secondary	Part 1 and Part 2: TTR for CNS (central nervous system) Metastases		Up to 4.5 years
Secondary	Part 1 and Part 2: DOR for CNS (central nervous system) Metastases		Up to 4.5 years