Trial Title:
A Study of NX-019 in Patients With Advanced, Epidermal Growth Factor Receptor (EGFR) Mutant Cancer
NCT ID:
NCT05514496
Condition:
EGFR Mutation-Related Tumors
Conditions: Keywords:
NX-019
EGFR Mutant Cancer
CNS Metastasis
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
NX-019
Description:
NX-019 will be administered orally.
Arm group label:
Part 1: NX-019 Dose Escalation
Arm group label:
Part 2: NX-019 Dose Expansion
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.
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
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).
Criteria for eligibility:
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 (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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Comprehensive Cancer Center - Duarte
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Facility:
Name:
City of Hope - Huntington Beach
Address:
City:
Huntington Beach
Zip:
92648
Country:
United States
Status:
Recruiting
Facility:
Name:
City of Hope Orange County Lennar Foundation Cancer Center
Address:
City:
Irvine
Zip:
92618
Country:
United States
Status:
Recruiting
Facility:
Name:
HealthPartners Frauenshuh Cancer Center
Address:
City:
Saint Louis Park
Zip:
55426
Country:
United States
Status:
Recruiting
Facility:
Name:
HealthPartners Cancer Center at Regions Hospital
Address:
City:
Saint Paul
Zip:
55101
Country:
United States
Status:
Recruiting
Facility:
Name:
University Of Virginia Comprehensive Cancer Center
Address:
City:
Charlottesville
Zip:
22903
Country:
United States
Status:
Recruiting
Facility:
Name:
NEXT Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Facility:
Name:
Seoul National University Hospital
Address:
City:
Seoul
Zip:
03080
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Severance Hospital
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Samsung Medical Center
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
National Taiwan University Cancer Center
Address:
City:
Taipei City
Zip:
10002
Country:
Taiwan
Status:
Recruiting
Start date:
October 5, 2022
Completion date:
October 17, 2027
Lead sponsor:
Agency:
Nalo Therapeutics Inc.
Agency class:
Industry
Source:
Nalo Therapeutics Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05514496