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

• ClinicalTrials.gov Identifier: NCT05514496
• Recruitment Status: Recruiting
• First Posted: August 24, 2022
• Last Update Posted: March 17, 2023
• Sponsor: Nalo Therapeutics Inc.
• Information provided by (Responsible Party): Nalo Therapeutics Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
EGFR Mutation-Related Tumors	Drug: NX-019	Phase 1

Detailed 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 Phase 2 Dose (RP2D).

Part 2: The primary objective of Part 2 of this study is to confirm the safety and tolerability of NX-019 at the MTD/RP2D and, for each expansion cohort, the preliminary evidence of efficacy as measured by objective response rate (ORR).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 178 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 5, 2022
• Estimated Primary Completion Date: February 17, 2027
• Estimated Study Completion Date: October 17, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1: NX-019 Dose Escalation; Patients will be treated with NX-019 in multiple ascending cohorts.	Drug: NX-019; NX-019 will be administered orally.
Experimental: Part 2: NX-019 Dose Expansion; Patients will be treated with the MTD/RP2D of NX-019 as determined in Part 1.	Drug: NX-019; NX-019 will be administered orally.

Outcome Measures

Primary Outcome Measures :

1. Part 1 and Part 2: Incidence of Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 4.5 years ]
2. Part 1 and Part 2: Incidence of Adverse Events of Special Interest (AESIs) [ Time Frame: Up to 4.5 years ]
3. Part 1 and Part 2: Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 4.5 years ]
4. Part 2: Objective response rate [ Time Frame: Up to 4.5 years ]

Secondary Outcome Measures :

1. Part 1: Objective response rate of NX-019 [ Time Frame: Up to 4.5 years ]
2. Part 1 and Part 2: Plasma Concentration of NX-019 [ Time Frame: Up to 43 days ]
3. Part 1 and Part 2: Cerebrospinal Fluid (CSF) Concentration of NX-019 [ Time Frame: Up to 43 days ]
4. Part 1 and Part 2: Maximum Observed Serum Concentration (Cmax) of NX-019 [ Time Frame: Up to 43 days ]
5. Part 1 and Part 2: Area under the concentration versus time curve (AUC) over a dosing interval (AUCtau) of NX-019 [ Time Frame: Up to 43 days ]
6. Part 1 and Part 2: AUC from time 0 to the time of last quantifiable plasma concentration (AUC0-t) of NX-019 [ Time Frame: Up to 43 days ]
7. Part 1 and Part 2: AUC from time 0 to infinity (AUC0-inf) of NX-019 [ Time Frame: Up to 43 days ]
8. Part 1 and Part 2: Percent of AUC extrapolated (AUC%extrap) of NX-019 [ Time Frame: Up to 43 days ]
9. Part 1 and Part 2: Terminal phase elimination half-life (t½) of NX-019 [ Time Frame: Up to 43 days ]
10. Part 1 and Part 2: Terminal phase elimination rate constant (λz) of NX-019 [ Time Frame: Up to 43 days ]
11. Part 1 and Part 2: Apparent plasma clearance (CL/F) of NX-019 [ Time Frame: Up to 43 days ]
12. Part 1 and Part 2: Apparent volume of distribution (Vd/F) of NX-019 [ Time Frame: Up to 43 days ]
13. Part 1 and Part 2: Accumulation index using Cmax (AICmax) and accumulation index using AUC (AIAUC0-inf) of NX-019 [ Time Frame: Up to 43 days ]
14. Part 1 and Part 2: Time to Response (TTR) [ Time Frame: Up to 4.5 years ]
15. Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Up to 4.5 years ]
16. Part 1 and Part 2: Disease Control Rate (DCR) [ Time Frame: Up to 4.5 years ]
17. Part 1 and Part 2: Overall Survival (OS) [ Time Frame: Up to 4.5 years ]
18. Part 1 and Part 2: Objective response rate for CNS (central nervous system) metastases [ Time Frame: Up to 4.5 years ]
19. Part 1 and Part 2: TTR for CNS (central nervous system) metastases [ Time Frame: Up to 4.5 years ]
20. Part 1 and Part 2: DOR for CNS (central nervous system) metastases [ Time Frame: Up to 4.5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.
• 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 3 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 EGFR mutant NSCLC (excluding ex20ins mutations) with CNS lesion(s), including asymptomatic leptomeningeal disease, which have progressed or been detected after prior therapy.

Expansion Cohort 2:

• Patients with EGFR ex20ins-mutant NSCLC with CNS lesion(s), including asymptomatic leptomeningeal disease.

Expansion Cohort 3:

• Patients with NSCLC and EGFR ex20ins mutations, and no prior ex20ins mutation targeted therapy.

Expansion Cohort 4:

• Patients with NSCLC and rare EGFR mutations for which there is no current targeted therapy, excluding exon 19, exon 21 L858R or L861Q, and ex20ins mutations.

Expansion Cohort 5:

• Patients with EGFR mutant NSCLC who meet Inclusion Criterion #1 and do not meet the specific requirements for Expansion Cohorts 1 through 4, after discussion with sponsor.

Exclusion Criteria:

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

• Known C797X EGFR mutations or known second driver of disease.
• 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) or unable to comply with ophthalmic guidance.
• History of interstitial lung disease, radiation pneumonitis which required systemic steroid therapy, or other significant lung disease.
• Has a history of another active malignancy (a second cancer).
• 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.
• 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.

Contacts and Locations

Contacts

Contact: Nalo Therapeutics; 323-909-6498; Info@nalotherapeutics.com

Locations

United States, California

City of Hope Comprehensive Cancer Center - Duarte; Recruiting

Duarte, California, United States, 91010

United States, Virginia

Virginia Cancer Specialists; Recruiting

Fairfax, Virginia, United States, 22031

Korea, Republic of

Seoul National University Hospital; Recruiting

Seoul, Korea, Republic of, 03080

Sponsors and Collaborators

Nalo Therapeutics Inc.

More Information

• Responsible Party: Nalo Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT05514496
• Other Study ID Numbers: NT019-101
• First Posted: August 24, 2022
• Last Update Posted: March 17, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• Supporting Materials: 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nalo Therapeutics Inc.:

NX-019; EGFR Mutant Cancer; CNS Metastasis