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

NCT05514496 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NT019-101
• Study Type: interventional
• Target: 258
• Locations: 3 countries
• Sites: 12

Brief 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.

Conditions

EGFR Mutation-Related Tumors

Keywords

NX-019; EGFR Mutant Cancer; CNS Metastasis

Outcome Measures

Primary Outcomes (4)

• Part 1 and Part 2: Incidence of Treatment-emergent Adverse Events (TEAEs)

  Up to 4.5 years

• Part 1 and Part 2: Incidence of Adverse Events of Special Interest (AESIs)

  Up to 4.5 years

• Part 1 and Part 2: Incidence of Serious Adverse Events (SAEs)

  Up to 4.5 years

• Part 2: Objective Response Rate

  Up to 4.5 years

Secondary Outcomes (21)

• Part 1: Progression-free Survival (PFS)

  Up to 4.5 years

• Part 1: Objective Response Rate of NX-019

  Up to 4.5 years

• 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)

• Part 1 and Part 2: Cerebrospinal Fluid (CSF) Concentration of NX-019

  Up to 43 days

• 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)

Study Arms (2)

Part 1: NX-019 Dose Escalation

EXPERIMENTAL

Patients will be treated with NX-019 in multiple ascending cohorts.

Drug: NX-019

Part 2: NX-019 Dose Expansion

EXPERIMENTAL

Patients will be treated with the REDs of NX-019 as determined in Part 1.

Drug: NX-019

Interventions

NX-019 DRUG

NX-019 will be administered orally.

Part 1: NX-019 Dose Escalation; Part 2: NX-019 Dose Expansion

Eligibility Criteria

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

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nalo Therapeutics Inc.: lead

Study Sites (12)

City of Hope Comprehensive Cancer Center - Duarte

Duarte, California, 91010, United States

Location

City of Hope - Seacliff

Huntington Beach, California, 92648, United States

Location

City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

Location

HealthPartners Frauenshuh Cancer Center

Saint Louis Park, Minnesota, 55426, United States

Location

HealthPartners Cancer Center at Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

University Of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

National Taiwan University Cancer Center

Taipei City, Taipei, 10002, Taiwan

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: August 24, 2022
• Study Start: October 5, 2022
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following final analysis.
• Access Criteria: Nalo will review on a case by case basis.

Locations

US (7); TW (1); KR (4)