Non-small Cell Lung Cancer
Conditions
Brief 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.
Interventions
DRUGDZD9008 plus Bevacizumab
DZD9008, 200 mg or 300 mg, once daily plus Bevacizumab 15 mg/kg, once every 3 weeks
Sponsors
Dizal Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: 1) Dose Limiting Toxicity (DLT); 2) Treatment-Emergent Adverse Events (TEAEs); TEAEs ≥CTCAE grade 3; and Serious Adverse Events (SAEs). Part B: 1) TEAEs; TEAEs ≥CTCAE grade 3; and SAEs. | The first treatment cycle (each cycle is 21 days) for DLT; From the first dose of study treatment to 28 days after the last dose of study treatment for TEAE; and from ICF signature to 28 days after the last dose of study treatment for SAE. | To investigate the safety and tolerability of DZD9008 in combination with Bevacizumab in patients with locally advanced NSCLC harboring EGFR mutations. Part A is a dose escalation study to determine the recommended phase 2 combination dose of DZD9008 and Bevacizumab. Part B is a dose expansion study to further investigate the safety and tolerability of the combination therapy at the recommended phase 2 combination dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: 1) Tumor response per RECIST 1.1 and 2) Plasma concentration of DZD9008 and its metabolite. Part B:1) Tumor response per RECIST 1.1; 2) Intracranial tumor response per RECISIT 1.1; 3) Plasma concentration of DZD9008 and its metabolite. | From the first dose of study treatment to disease progression, death or study withdrawal, whichever occurs first; and Cycle 1/3/5/7 day 1 (each cycle is 21 days) for plasma concentration of DZD9008 and its metabolite. | To investigate the anti-tumor efficacy of DZD9008 in combination with Bevacizumab and the pharmacokinetics of DZD9008 and its metabolite DZ0753 when given in combination with Bevacizumab. The efficacy endpoints per RECIST 1.1 include Objective Response Rate (ORR), Duration of Response (DoR),Disease Control Rate (DCR), and Progression Free Survival (PFS). |
Countries
China
Contacts
Primary ContactYiman Wang, MD, PhD
Outcome results
None listed