Trial Title:
DZD9008 In Combination With Bevacizumab in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutation (WU-KONG29)
NCT ID:
NCT06276283
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Bevacizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
DZD9008 plus Bevacizumab
Description:
DZD9008, 200 mg or 300 mg, once daily plus Bevacizumab 15 mg/kg, once every 3 weeks
Arm group label:
DZD9008 plus Bevacizumab
Other name:
Inapplicable
Summary:
This study tests a combination therapy (i.e., DZD9008 plus bevacizumab) in patients with
advanced NSCLC harboring EGFR mutations who have progressed on or after standard of care,
which aims to understand whether the combination therapy is safe, how well the
combination therapy works, and how the body will process DZD9008 when used in combination
with bevacizumab.
Detailed description:
A phase 2, multicenter study to evaluate the safety, tolerability, and anti-tumor
efficacy in patients with locally advanced or metastatic NSCLC harboring EGFR mutations.
This study comprises two parts (Part A, dose escalation and Part B, dose expansion). Part
A will enroll patients with different EGFR mutations. Only patients with EGFR Exon 20
insertion mutation will be enrolled into Part B.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patients must meet all the following criteria for inclusion in the study:
1. Sufficient understanding of nature of the trial and provision of informed consent
with hand-written signatures and the date of signature prior to any study-specific
procedures, sampling, and analyses.
2. Age ≥ 18 years.
3. Histologically or cytologically confirmed and locally advanced or metastatic
non-squamous NSCLC.
4. Written documentation of EGFR mutations from an accredited local laboratory: Part A
is not limited to a specific EGFR mutation, and Part B only includes patients with
EGFR Exon20ins.
5. ECOG score ≤ 1 without clinically significant disease deterioration within 2 weeks
prior to the informed consent process and a life expectancy ≥ 12 weeks.
6. Patients with stable brain metastasis provided no evidence of progression for at
least 2 weeks, as ascertained by brain imaging (magnetic resonance imaging [MRI] or
computed tomography [CT] scan) during the screening period, no neurological
symptoms, and no requirement of Steroids.
7. Part A includes patients who have progressed after or cannot tolerate the standard
of care
8. Part B includes patients with NSCLC who have progressed after or cannot tolerate
standard of care. Treatment naïve patients will be enrolled after an adequate
evaluation of the safety data by the Safety Review Committee (Note: Patients who
have received (neo)adjuvant therapy are allowed to participate in the study, if the
(neo)adjuvant therapy is administrated at least 6 months prior to the diagnosis of
locally advanced or metastatic NSCLC) .
9. Measurable lesions, according to RECIST 1.1: at least one lesion, not previous
irradiated, with the longest diameter ≥ 10 mm at baseline (lymph nodes must have a
short axis of ≥ 15 mm), that can be accurately measured at baseline and thereafter
with MRI or CT scan.
10. Male patients with a female partner or fertility desire should be willing to use
barrier contraception (e.g., condoms) until 6 months after the last dose. Male
patients should not donate sperms until 6 months after the last dose. Male patients
with fertility desire are suggested to freeze their sperm before entering the study.
11. Female patients should be willing to use adequate contraceptive measures, should not
be breastfeeding, and must have a negative pregnancy test (i.e., urine and blood
pregnancy human chorionic gonadotropin testing); or female patients meet the
following criteria:
- Post-menopausal defined as age more than 60 and amenorrheic for at least 12
months after all exogenous hormonal treatments.
- Women under 60 years old would be considered post-menopausal if they have been
amenorrheic for at least 12 months with luteinizing hormone (LH) and
follicle-stimulating hormone (FSH) levels in the post-menopausal range.
- Documentation of irreversible surgical sterilization (e.g., hysterectomy,
bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation).
Exclusion Criteria:
Patients must not enter the study if any of the following exclusion criteria are met:
1. Treatment with any of the following:
- Treatment with poziotinib, mobocertinib (TAK788), CLN-081, BDTX-189,
aumolertinib, AP-L1898, and other EGFR Exon20ins inhibitors prior to the first
dose of study drug (only applicable to Part B).
- Prior treatment with 1st to 3rd generation EGFR-TKIs (e.g., gefitinib,
erlotinib, icotinib, osimertinib, afatinib, dacomitinib, and ametinib) and have
had an objective response (i.e., PR and CR) (only applicable to Part B).
- Prior systemic treatment for locally advanced or metastatic NSCLC (only
applicable to treatment naïve patients in Part B)
- Treatment with EGFR, HER2, or VEGFR antibody within 4 weeks of the first dose
of study drug.
- Chemotherapy or other anti-tumor therapies within 2 weeks of the first dose of
study drug.
- Radiotherapy within 14 days of the first dose of study drug or unresolved
radiotherapy-related toxicities. Patients could receive palliative radiotherapy
for tumor lesions outside of brain and chest, stereotactic radiosurgery, and
stereotactic body radiotherapy.
- Current treatment within 1-2 weeks of the first dose of study drug with
medications or herbal supplements known to be potent inhibitors (1 week) or
inducers (2 weeks) of cytochrome P450 (CYP) 3A4.
- Major surgery, excluding biopsy and diagnostic surgery, within 4 weeks of the
dose of study drug, or expected major surgeries during the study period.
- Treatment with an investigational drug within 5 half-lives of the compound.
Patient
2. Spinal cord compression or leptomeningeal metastasis.
3. Concurrent EGFR mutations with approved EGFR-TKIs (e.g., Exon19del, L858R, T790M,
G718X, S768I and L861Q; only applicable to Part B).
4. History of malignancy within 2 years of the first dose of study drug (excluding
adequately treated Basal cell carcinoma or in situ cervical cancer with a tumor-free
period of more than 2 years and a life expectancy of more than 2 years. The
inclusion of such patients should be discussed with the study physician from Dizal
Pharma).
5. Any unresolved toxicities from prior systemic therapy (e.g., adjuvant chemotherapy
and radiotherapy) > CTCAE grade 1 at the time of starting study drug except for
alopecia and grade 2 neuropathy related to previous platinum-based therapy.
6. History of stroke and intracranial hemorrhage within 6 months of the first dose of
study drug.
7. Any evidence of severe or uncontrolled systematic disease based on the
investigator's opinion, including uncontrolled hypertension and active bleeding
diatheses (e.g., hemophilia and von Willebrand disease).
8. Any evidence of active infection, including but not limited to hepatitis B,
hepatitis C, human immunodeficiency virus (HIV), and COVID-19. The diagnosis of
COVID-19 follows the local practice.
Test Include if Exclude if HIV antibody (-) (+) HCV antibody (-) (+) HBV antibody
HbsAg (-) and HbcAb (-) HbsAg (+) and HBV DNA ≥ 1000 IU/mL HbsAg (-), HbcAb (+) and
HBV DNA < 1000 IU/mL HbsAg (-), HbcAb (+), and HBV DNA ≥ 1000 IU/mL (-), Negative;
(+), Positive.
9. Any of the following cardiac events or abnormalities:
- Mean resting corrected QT interval (QTcF) > 470 msec.
- Any clinically significant abnormalities in rhythm, conduction, or morphology
detected by resting ECG, e.g., complete left bundle branch block, third-degree
heart block, second-degree heart block, and PR interval > 250 msec.
- Any factors that can lead to QTcF prolongation or arrhythmia, such as heart
failure, hypokalemia, congenital long QT syndrome, family history of long QT
syndrome, family history of unexplained sudden death under 40 years of age, or
any comorbidities known to prolong the QT interval.
- Any evidence of atrial fibrillation (except for drug-related atrial
fibrillation that has been resolved after drug discontinuation).
- Any evidence of myocadiac infraction, congestive heart failure (New York Heart
Association Class II or above), and uncontrolled arrhythmia with medication
within 6 months of the first dose of study drug.
10. History of interstitial lung disease (ILD), drug-induced ILD, and immune-related
pneumonitis due to cancer immunotherapy.
11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty
swallowing the study drug, or previous bowel resection that would preclude adequate
absorption of DZD9008.
12. Inadequate bone marrow reserve or organ function:
- Absolute neutrophil count < 1.5 × 109/L
- Platelet count < 100 ×109/L
- Hemoglobin < 9 g/dL
- Total bilirubin >1.5 × ULN if no liver metastases or >3 × the upper limit of
normal (ULN) in the presence of documented Gilbert's Syndrome (unconjugated
hyperbilirubinemia) or liver metastases
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST >2.5 × ULN
if no demonstrable liver metastases or >5 × ULN in the presence of liver
metastases.
- Creatinine ≥1.5 × ULN or creatinine clearance <50 mL/min (measured or
calculated by Cockcroft and Gault equation)
- The international normalized ratio > 1.5 × ULN and activated partial
thromboplastin time (APTT) > 1.5 × ULN
- Serum lipase) > 1.5 × ULN and serum amylase > 1.5 × ULN
13. Live virus vaccines administrated within 2 weeks of the first dose of study drug.
14. Pregnant women or women who are breastfeeding.
15. Concurrent contraindications to bevacizumab, including but not limited to:
- Deep vein thrombosis ≥ CTCAE grade 3
- Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic
blood pressure ≥ 100 mmHg)
- Intracerebral hemorrhage, including hemorrhage caused by metastatic brain
tumors.
- History of severe proteinuria (urine dipstick protein 2+ or 24-hour urine
protein > 2g)
- History of hypertensive crisis and hypertensive encephalopathy
- History of central nervous system diseases that are not related to the tumor
(e.g., convulsions)
- History of vascular events within 6 months of the first dose of study drug
(e.g., aneurysm requiring treatment)
- History of hemoptysis within 3 months of the first dose of study drug (two
spoonfuls of blood each time)
- History of bleeding disorders or coagulation disorders without treatment of
anticoagulants.
- Tumor invasion of major vessels
- History of gastrointestinal perforation or fistula within 6 months of the first
dose of study drug
16. Severe allergic reaction to DZD9008, bevacizumab, or their excipients.
17. Subjects who are involved in the design, planning, or conduct of the study
(applicable to employees of Dizal Pharm and staff at investigational sites).
18. Poor compliance or inability to participate in clinical studies according to the
investigator's assessment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Chest Hospital
Address:
City:
Shanghai
Zip:
200030
Country:
China
Status:
Recruiting
Contact:
Last name:
Lu, Dr
Start date:
February 15, 2023
Completion date:
February 28, 2026
Lead sponsor:
Agency:
Dizal Pharmaceuticals
Agency class:
Industry
Source:
Dizal Pharmaceuticals
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06276283
