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.
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.
Age ≥ 18 years.
Histologically or cytologically confirmed and locally advanced or metastatic non-squamous NSCLC.
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.
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.
Single group
DZD9008 plus Bevacizumab
DrugDZD9008, 200 mg or 300 mg, once daily plus Bevacizumab 15 mg/kg, once every 3 weeks
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.
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.
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.
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).
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