Trial Title:
Phase I/IIa Study of H002 in NSCLC With Active EGFR Mutation
NCT ID:
NCT05519293
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Dose-escalation and Expansion
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
H002
Description:
Small molecule, Capsule
Arm group label:
150 mg QD, oral
Arm group label:
20 mg QD, oral
Arm group label:
250 mg QD, oral
Arm group label:
350 mg QD, oral
Arm group label:
40 mg QD, oral
Arm group label:
80 mg QD, oral
Summary:
This is a phase I/IIa, open-label, dose-escalation and expansion study to evaluate the
safety, tolerability, PK and preliminary anti-tumor activity of H002 when given orally in
patients with active EGFR mutation locally advanced or metastatic non-small cell lung
cancer (NSCLC).
The study will contain two parts: Part A is dose escalation phase (i.e., Phase I) and
Part B is dose expansion phase (i.e., Phase IIa).
Detailed description:
Part A (Dose Escalation Phase) Approximately 36 subjects will be enrolled, based on the
"3+3" design for dose escalation and safety evaluation requirements. The total number of
subjects will depend upon the number of dose escalations necessary.
Part B (Dose Expansion Phase) Up to 20 subjects will be enrolled in each expansion arm,
the total number of subjects will depend upon the number of dose expansions (expansions
may be at more than one dose depending upon emerging data).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Males or females aged ≥ 18 years at time of signing informed consent form (ICF).
2. Histological or cytological confirmed diagnosis of unresectable locally advanced or
metastatic NSCLC.
3. Subjects must have NSCLC harboring one or more active EGFR mutations known to be
associated with EGFR-TKI sensitivity (including, but not limited to Del19 and
L858R).
- Part A: All subjects may provide tumor sample to central laboratory to analyze
the EGFR mutation status according to their own willingness;
- Part B: All subjects must provide tumor sample to central laboratory to analyze
the EGFR mutation status. And subjects must have NSCLC harboring EGFR C797S
mutation.
Note: Tumor sample can be either an archival sample or a sample obtained by
pretreatment biopsy prior to H002 treatment.
4. Subjects must have radiological documented disease progression while on a previous
continuous treatment with osimertinib or another third-generation EGFR-TKI as well
as disease progression on the last treatment administered prior to enrolling in the
study.
5. Presence of at least one measurable lesion according to RECIST v1.1 per investigator
assessment.
6. ECOG performance status of 0-1.
7. Life expectancy ≥ 12 weeks.
8. Adequate hematologic and organ function per protocol.
9. Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must
use highly effective contraception per protocol throughout the study. WOCBP must
have a negative serum and/or urine pregnancy test result within 7 days prior to the
first dose of H002.
10. Signed ICF, and this must be obtained before the performance of any
protocol-specific procedures.
Exclusion Criteria:
1. Treatment with any of the following:
Prior treatment with an EGFR-TKI within 8 days or approximately 5 × t1/2 prior to
the first dose of H002, whichever is longer; Prior treatment with immunotherapy or
biotherapy within 4 weeks prior to the first dose of H002; Radiotherapy (palliative
radiotherapy is completed at least 2 weeks prior to the first dose of H002 can be
enrolled) within 4 weeks prior to the first dose of H002; Herbal therapy that has
anti-tumor effects within 2 weeks prior to the first dose of H002; Mitomycin and
nitrosourea within 6 weeks prior to the first dose of H002; Oral fluorouracil such
as tegafur and capecitabine within 2 weeks prior to the first dose of H002;
Chemotherapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs), or
other anti-tumor drugs for the treatment of NSCLC within 4 weeks or approximately 5
× t1/2 prior to the first dose of H002, whichever is longer.
2. Subjects with EGFR exon 20 insertion mutations only.
3. Prior marketed and/or investigational treatment for EGFR C797S mutation (including,
but not limited to BTP-661411, TQB3804 and BLU-945).
4. Is currently participating and receiving investigational therapy or using an
investigational device, or has participated in a study of an investigational agent
and received study therapy or used an investigational device within 4 weeks or 5 ×
t1/2 of the investigational product, whichever is longer, prior to the first dose of
H002.
5. Is expected to require any other form of anti-tumor therapy while on study.
6. Unresolved toxicity greater than CTCAE v5.0 Grade 1 from prior anti-tumor therapy.
7. ≥ CTCAE v5.0 Grade 2 skin toxicity at screening.
8. Treatment with strong inhibitors, strong inducers and sensitive substrates of
CYP3A4, substrates and inhibitors for P-glycoprotein (P-gp), as well as substrates
for breast cancer resistance protein (BCRP) within 2 weeks prior to the first dose
of H002, or anticipation of need for such drugs during study treatment.
9. Uncontrollable pleural effusion, ascites, or pericardial effusion.
10. Subjects who have symptomatic brain metastases, meningeal metastasis or spinal cord
compression.
11. Subjects who have a chronic or active infection that required systemic treatment
within 2 weeks prior to the first dose of H002.
12. Subjects who have gastrointestinal disorders that will affect oral administration or
the investigator judges that the absorption of H002 will be interfered.
13. History of hypersensitivity to active or inactive excipients of H002 or drugs with a
similar chemical structure or class to H002.
14. Subjects who received a diagnosis of, and/or tested positive at screening for human
immunodeficiency virus (HIV).
15. Subjects with active hepatitis B.
16. Presence or history of malignancy other than NSCLC with the exception of some
certain early-stage cancers.
17. Subjects who have clinically significant cardiovascular diseases that occurred
within 6 months prior to the first dose of H002, include but not limited to QTc
interval ≥ 470 msec.
18. Major surgery or significant traumatic injury occurring within 4 weeks prior to the
first dose of H002 or anticipation of need for a major surgery during the study.
19. Medical history of ILD.
20. Medical history of severe eye disease without recovery to CTCAE v5.0 Grade 0 or 1.
21. Severe gastrointestinal disease within 4 weeks prior to the first dose of H002 and
did not recover to ≤ CTCAE v5.0 Grade 2.
22. Has any bleeding tendency or coagulopathy within 6 months prior to the first dose of
H002.
23. Has known psychiatric disorders that would interfere with cooperation with the
requirements of the trial or is still requiring for medication control.
24. Administration of a live, attenuated vaccine within 4 weeks prior to the first dose
of H002 or anticipation of need for such a vaccine during the study. Administration
of an mRNA Corona Virus Disease 2019 (COVID-19) vaccine within 72 hours prior to the
first dose of H002.
25. Female subjects in pregnancy or lactation.
26. Any other circumstances that would, in the investigator's judgment, prevent the
subject's participation in the clinical study due to safety concerns or compliance
with clinical study procedures.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Valkyrie Clinical Trials
Address:
City:
Los Angeles
Zip:
90067
Country:
United States
Status:
Recruiting
Contact:
Last name:
David Berz, MD
Phone:
424-535-1874
Email:
david.berz@valkyrieclinicaltrials.com
Contact backup:
Last name:
Francisco Capilla
Phone:
(424) 535-1874
Email:
Francisco.capilla@valkyrieclinicaltrials.com
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Julia Rotow, MD
Phone:
617-582-8844
Email:
Julia_Rotow@DFCI.HARVARD.EDU
Contact backup:
Last name:
Kathryn Miller, MPH
Phone:
617-582-8844
Email:
kathrynw_miller@dfci.harvard.edu
Facility:
Name:
Columbia University
Address:
City:
New York
Zip:
10032
Country:
United States
Status:
Recruiting
Contact:
Last name:
Catherine Shu, MD
Phone:
212-305-3248
Email:
cas2145@cumc.columbia.edu
Contact backup:
Last name:
Robert Garofano, MA
Phone:
212-305-3248
Email:
rfg2115@cumc.columbia.edu
Facility:
Name:
NEXT Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alex Spira
Phone:
703-280-5390
Email:
aspira@nextoncology.com
Investigator:
Last name:
Alex Spira, MD
Email:
Principal Investigator
Start date:
December 15, 2022
Completion date:
February 28, 2025
Lead sponsor:
Agency:
RedCloud Bio
Agency class:
Industry
Collaborator:
Agency:
Parexel
Agency class:
Industry
Source:
RedCloud Bio
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05519293
