DZD9008 In Combination With Bevacizumab in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutation (WU-KONG29)

NCT06276283 | Recruiting Phase 2

• 1 other identifier: DZ2022E0006
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Secondary Outcomes (1)

• 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.

Study Arms (1)

DZD9008 plus Bevacizumab

EXPERIMENTAL

This single-arm study includes two parts (dose escalation \[Part A\] and dose expansion \[Part B\]).

Drug: DZD9008 plus Bevacizumab

Interventions

DZD9008 plus Bevacizumab DRUG

DZD9008, 200 mg or 300 mg, once daily plus Bevacizumab 15 mg/kg, once every 3 weeks

Also known as: Inapplicable

DZD9008 plus Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG score ≤ 1 without clinically significant disease deterioration within 2 weeks prior to the informed consent process and a life expectancy ≥ 12 weeks.
• 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.
• Part A includes patients who have progressed after or cannot tolerate the standard of care
• 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) .
• 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.
• 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.
• 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).

You may not qualify if:

• 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
• Spinal cord compression or leptomeningeal metastasis.
• Concurrent EGFR mutations with approved EGFR-TKIs (e.g., Exon19del, L858R, T790M, G718X, S768I and L861Q; only applicable to Part B).
• 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.
• History of stroke and intracranial hemorrhage within 6 months of the first dose of study drug.
• 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).

Sponsors & Collaborators

• Dizal Pharmaceuticals: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lu

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yiman Wang, MD, PhD

CONTACT

+ 86 21 6109 7885; yiman.wang@dizalpharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2024
• First Posted: February 23, 2024
• Study Start: February 15, 2023
• Primary Completion: December 31, 2025
• Study Completion: February 28, 2026
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)