Trial Title:
To Evaluate the Efficacy of QLH11811 in Advanced NSCLC Patients With EGFR Mutation
NCT ID:
NCT05555212
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
This is a phase 1, open-label, dose escalation and cohort expansion study and conducted
in China and the United States to investigate the safety, tolerability and preliminary
efficacy of QLH11811 in advanced or metastatic NSCLC patients who have progressed after
prior EGFR-TKI treatment. The study consists of the following 2 phases: phase 1: dose
escalation (1a) and phase 2: cohort expansion (1b), as detailed in Overall Schematic of
Study Design. Phase 1a: this dose escalation study will be conducted in China and the
United States, respectively, and the dose escalation will start from starting dose in
China and from dose level next to the MTD determined in Chinese subjects in the United
States. Phase 1b: after the determination of RP2D, this cohort expansion study will be
conducted in China and the United States concurrently to observe the safety, tolerability
and efficacy of QLH11811 in advanced NSCLC patients who have EGFR mutation
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
QLH11811
Description:
In Ia phase, subjects will first receive oral single dose of QLH11811, then will be
observed for 7 days. If the drug is tolerated by the subjects, the subjects will continue
to receive the oral repeat dose of QLH11811 for 21 consecutive days. Upon the completion
of observation for DLT in the subjects (DLT observation period is the 28 days after the
first dose), the subjects will continue to receive the repeat dose of QLH11811 in Cycle 2
and subsequent cycles. The dosing frequency in Cycle 2 and subsequent cycles is once
daily, and each cycle has 3 weeks.
The RP2D of QLH11811 is determined on the basis of comprehensive evaluation of all safety
and tolerability data and all available PK, PD and efficacy data during the dose
escalation phase. In phase 1b, the cohort expansion study is carried out for all cohorts
in China and the United States concurrently according to the determined RP2D.
Arm group label:
dose escalation (in China)
Summary:
This is a phase 1, open-label, dose escalation and cohort expansion study and conducted
in China and the United States to investigate the safety, tolerability and preliminary
efficacy of QLH11811 in advanced or metastatic NSCLC patients who have progressed after
prior EGFR-TKI treatment. The study consists of the following 2 phases: phase 1: dose
escalation (1a) and phase 2: cohort expansion (1b).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients who participate voluntarily, sign informed consent form (ICF), and will be
able to follow the study procedures;
2. Aged ≥ 18 years;
3. Patients who are histologically or cytologically diagnosed with EGFR mutation and
have unresectable locally advanced or recurrent/metastatic NSCLC;
4. EGFR mutation requirements:
Dose escalation phase (phase 1a): NSCLC patients who have progressed after standard
EGFR-TKI treatment or cannot tolerate standard of care;
Cohort expansion phase (phase 1b):
1. Cohort 1: advanced NSCLC patients who have progressed after treatment with
third-generation EGFR-TKIs and have EGFR C797S mutation.
2. Cohort 2: advanced NSCLC patients who have progressed after standard EGFR-TKI
treatment but have no other additional driver gene mutation(s).
3. Cohort 3: advanced NSCLC patients who have progressed after EGFR-TKI treatment
and have T790M mutation.
4. Cohort 4: patients with locally progressed, unresectable or recurrent
metastatic NSCLC who are naive to EGFR-TKI treatment and have 19del or 21L858R
mutation among EGFR sensitive mutations.
5. Patients who agree to provide tumor samples (fresh tissues or archived samples) for
analysis of EGFR gene.
Dose escalation phase: tumor samples collected from the progression site of disease
during or after PD after the last TKI treatment should be provided for new genetic
testing The subjects who fail to provide tumor samples will be allowed to enroll
only after communication and consultation with the sponsor.
Cohort expansion phase:
Cohort1: tumor samples collected from the progression site of disease during or
after PD after the last TKI treatment should be provided for genetic testing at
central laboratory.
Cohorts 2 and 3: tumor samples collected from the progression site of disease during
or after PD after the last TKI treatment should be provided for genetic testing. The
genetic testing will be exempted if subjects have the test results meeting the above
requirements before their enrollment.
Cohort 4: tumor samples collected from the progression site of disease during or
after PD after the last treatment should be provided for genetic testing (of EGFR
mutation); and if subjects are treatment-naive, they will be required to provide the
tumor samples only during the screen period. The genetic testing will be exempted if
subjects have the test results meeting the above requirements before their
enrollment.
6. ECOG ≤ 1 point (for details, refer to Appendix 2 ECOG performance status score);
7. Life expectancy ≥ 12 weeks;
8. Patients who have been diagnosed according to RECIST v1.1 and have measurable
lesions as documented by computed tomography (CT) and/or magnetic resonance imaging
(MRI) (note: subjects who do not have measurable lesions are allowed to be enrolled
in phase 1a study). Note: a measurable lesion for response evaluation has to meet
the following criteria: a) it is not in an area that has been involved in prior
radiotherapy, or b) there is notable radiographic evidence of progression after the
completion of radiotherapy and before study enrollment;
9. Patients who have adequate organ functions and meet the following criteria:
1. Hematology:
Absolute neutrophil count ≥ 1.5 × 109/L; platelet count ≥ 100 × 109/L;
hemoglobin ≥ 90 g/L (no blood transfusion and no use of granulocyte colony
stimulating factor in the 14 days prior to the screening);
2. Coagulation:
For patients who have not received anticoagulant therapy: international
normalized ratio (INR) of prothrombin time and partial thromboplastin time ≤
1.5 × ULN;
3. Liver:
Alanine aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3.0 × ULN.
For patients with liver metastases: ALT and AST ≤ 5 × ULN, total bilirubin ≤
1.5 × ULN. For patients with Gilbert syndrome: conjugated bilirubin within
normal range;
4. Kidney:
Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (calculated
according to Cockcroft-Gault formula, refer to Appendix 4 Creatinine clearance
calculation formula).
10. All acute toxic reactions arising from prior antineoplastic therapy or surgery have
resolved to baseline or reduced in severity to ≤ Grade 1 according to NCI CTCAE V5.0
(except for alopecia or other toxicities which, in the opinion of the investigator,
pose no safety risk to the patient);
11. Patients (both female and male) who agree to take effective contraceptive measures
from their signing of ICF to 6 months after the last dose of the study drug. For
women of childbearing potential: negative serum pregnancy test result in 7 days
prior to the start of treatment is required.
Exclusion Criteria:
1. Patients who have received systemic anticancer therapies (e.g., chemotherapy,
molecularly targeted therapy, radiotherapy, biotherapy, hormone therapy, vaccine
therapy), or antineoplastic TCM therapy in the 2 weeks prior to the first dose of
study treatment; or who have received immune-checkpoint inhibitor therapy in the 4
weeks prior to the first dose of study treatment;
2. Patients who have received radical radiotherapy (including radiotherapy of more than
25% of bone marrow) in the 4 weeks prior to the first dose, or who have received
local palliative radiotherapy for bone metastatic lesions in the 1 week prior to the
first dose;
3. Patients who have received strong or moderate CYP3A, P-gp inhibitors in the 1 week
prior to the first dose or in 5 half-lives of these drugs (whichever is longer), or
need to continue to receive these drugs during the study; and who have received
strong or moderate CYP2B6, CYP1A2 and CYP3A inducers in the 4 weeks prior to the
first dose;
4. Patients who are in the treatment period of other interventional clinical studies in
the 4 weeks prior to the first dose. However, participants of non-interventional
clinical studies (e.g., epidemiologic studies) are eligible for enrollment in this
study. Patients in the survival follow-up period of interventional clinical studies
are also eligible for enrollment in this study;
5. Patients who have active bacterial, fungal or viral infection requiring systemic
therapies within the 1 week prior to the first dose;
6. Patients who have underwent a major operation (e.g., a surgical operation requiring
local or general anesthesia and hospitalization) in the 3 weeks prior to the start
of study treatment;
7. Patients with a history of chronic diarrhea, including but not limited to Crohn's
disease, irritable bowel syndrome, etc.;
8. Patients who have experienced > CTCAE Grade 1 continuous diarrhea within the 1 week
prior to the first dose;
9. Patients with serious respiratory disorders, e.g. interstitial lung disease,
radiation pneumonitis, drug-induced pneumonia (however, patients whose conditions
have resolved and stabilized for 3 months or more are eligible for enrollment);
10. Patients with symptomatic metastasis to central nervous system (CNS) and/or with
meningitis carcinomatosa.
Note: patients with brain metastases whose clinical symptoms have stabilized after
treatment are eligible for participation in the study, provided that their
conditions are radiographically stabilized (defined as stability demonstrated by 2
brain images acquired by the same imaging technique after treatment of brain
metastases). These imaging scans should be carried out at an interval of at least 4
weeks, and show no signs of intracranial progression. Furthermore, brain metastases
or its treatment induced neurologic symptoms need to regress to baseline level or
resolve. All steroids administered as a part of the treatment must be completed ≥ 3
days prior to the administration of study treatment.
11. Patients with clinically significant cardiovascular and cerebrovascular diseases,
including but not limited to:
1. Myocardial infarction or unstable angina in the 6 months prior to the first
dose;
2. Stroke or transient ischemic attack in the 6 months prior to the first dose;
3. Any clinically significant abnormalities in resting ECG in terms of cardiac
rhythm, heart rate, conduction or morphology, e.g. complete left bundle branch
block, third-degree conduction block, second-degree conduction block, PR
interval > 250 ms, etc.;
4. Uncontrolled hypertension after active treatment: systolic pressure > 180 mmHg
or diastolic pressure > 100 mmHg;
5. Congestive cardiac failure (NYHA functional class III-IV);
6. Pericarditis or clinically significant pericardial effusion;
7. Myocarditis;
8. 12-lead ECG shows that mean QT interval (QTcF) > 450 ms (male) or > 470 ms
(female) before the first dose of investigational drug;
9. Failure to discontinue the drugs that may cause QTc prolongation or torsades de
pointes (e.g., antiarrhythmics) during the study.
12. Patients with clinically uncontrolled serous effusion(e.g., pleural fluid that
cannot be controlled by drainage or other methods).
13. Patients with active gastrointestinal disorders or other conditions that have
serious interference with the drug absorption.
14. Patients with any condition that have an adverse impact on the swallowing of the
drug or on the absorption or PK parameters of the investigational drug;
15. Patients with known serious allergy to the study drug or any excipient of the drug;
16. Patients with known HIV test positive result and/or treponema pallidum antibody test
positive result (except for those whose infection has been cured after treatment).
17. Patients with HBsAg positive result and HBV DNA > 2000 IU/mL or 104 copies/mL (for
sites which only provide the qualitative testing, HBV DNA test result is positive or
higher than lower limit of detection); or with HCV antibody positive and HCV RNA
positive results.
18. Patients who experienced other malignancies (with the exceptions of Bowen's disease;
cured basal cell or squamous cell skin cancer; prostate cancer with a Gleason score
of 6; treated cervical carcinoma in situ) in the 2 years prior to the study
enrollment.
19. Pregnant or lactating women. Lactating female subjects need to stop breast-feeding
before the first dose of study treatment, which cannot be resumed throughout the
study and in the 6 months after the last dose of study treatment.
20. Patients with any existing serious or unstable diseases (except for the
above-mentioned malignancies), psychiatric disorders or any disease or medical
condition which, in the investigator's opinion, may have an adverse impact on the
subject safety, the signing of ICF or the compliance with the study procedures.
21. Patients who are currently participating in a clinical study of other
investigational therapies.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Qilu Pharmaceutical.Co.,Ltd
Address:
City:
Jinan
Zip:
273200
Country:
China
Status:
Recruiting
Contact:
Last name:
kang
Phone:
0531-83126666
Email:
xiaoyan.kang@qilupharma.com
Start date:
October 25, 2022
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Qilu Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Qilu Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05555212
