DZD6008 plus chemotherapy for advanced EGFR‑mutant non‑small cell lung cancer

A Phase 1/2, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Efficacy of DZD6008 Combination Therapy in Patients With Locally Advanced or Metastatic NSCLC With EGFR Mutation (TIAN-SHAN7)

This tests whether DZD6008 combined with chemotherapy is safe and can shrink tumors in adults with advanced EGFR‑mutant non‑small cell lung cancer who have progressed after EGFR TKIs.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Dizal Pharmaceuticals (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07070440 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 study gives patients with locally advanced or metastatic non‑squamous NSCLC and confirmed EGFR sensitizing mutations a regimen that combines the experimental agent DZD6008 with standard chemotherapies (pemetrexed, carboplatin, or docetaxel) to determine safety, tolerability, and antitumor activity. Eligible patients must have progressed after prior EGFR tyrosine kinase inhibitors, have measurable disease by RECIST 1.1, and adequate bone marrow function with ECOG 0–1. Tumor tissue and plasma samples will be collected for central EGFR mutation analysis and response monitoring. The trial is conducted at Shanghai Chest Hospital with close monitoring for adverse events and dose‑limiting toxicities.

Who should consider this trial

Good fit: Adults (≥18) with locally advanced or metastatic non‑squamous NSCLC harboring a confirmed EGFR sensitizing mutation, measurable disease, ECOG 0–1, adequate bone marrow function, and prior failure of EGFR TKIs are ideal candidates.

Not a fit: Patients without EGFR sensitizing mutations, with squamous histology, uncontrolled symptomatic brain metastases, poor performance status (ECOG ≥2), or inadequate organ function are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option that controls tumor growth for patients whose cancers have progressed after EGFR targeted therapies.

How similar studies have performed: Combining targeted agents with chemotherapy after EGFR TKI failure has shown mixed benefits in prior studies, and DZD6008 itself is a novel investigational agent with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent.
2. Age ≥18 years old.
3. Locally advanced or metastatic non-squamous non-small cell lung cancer by histopathology or cytology, not suitable for other radical treatment.
4. Documentation of EGFR sensitizing mutation confirmed by local laboratory.
5. Provide sufficient tumor tissue samples and plasma samples for retrospective analysis of EGFR mutations by central laboratory.
6. Failure of prior 3 generations EGFR TKI.
7. ECOG status score 0-1, life expectancy ≥12 weeks.
8. No central nervous system symptoms during screening, no need for corticosteroids or dehydration diuretic treatment for at least 4 weeks before the first dosing. If the patient with brain metastasis has received radiotherapy or surgery, there is a washout period of ≥2 weeks before the first use of DZD6008 and ensure that the AE related to radiotherapy or surgery has recovered to ≤ 1 grade.
9. Presence of measurable lesions defined by RECIST 1.1.
10. Sufficient bone marrow or other organ reserve before first dosing.

Exclusion criteria

1. Histology mixed with small cell lung cancer (SCLC) or with SCLC transformation.
2. Received the following treatments or had the following lifestyle habits, etc.:

   * Received immunotherapy or other antibody treatments (including EGFR-targeted antibodies, bispecific antibodies or antibody-drug conjugates, etc.) within 4 weeks before the first study drug administration.
   * Received any cytotoxic chemotherapy, study drugs or other anti-cancer drugs (excluding macromolecule drugs) within 14 days before the first study drug administration.
   * Received limited-range radiotherapy to relieve the disease within 7 days before the first study drug administration, or received more than 30% of the bone marrow radiotherapy or received wide-range radiotherapy within 28 days before the first medication.
   * 2 weeks (for CYP3A4 inhibitors) or 3 weeks (for CYP3A4 inducers) before the first study drug administration, are taking or cannot stop taking known cytochrome P450 (CYP) 3A4 strong inhibitors or inducers (including herbal supplements, such as St. John's wort).
   * 2 weeks before the first study drug administration, are taking or cannot stop taking known CYP3A4 sensitive substrate drugs (with a narrow therapeutic window).
   * Taking or being unable to stop taking drugs known to be proton pump inhibitors within 1 week before the first study drug administration.
   * Major invasive surgery has been performed within 4 weeks before the first study drug administration or is planned during treatment.
3. Presence of AEs of ≥1 grade (except any degree of alopecia) caused by previous treatment (such as adjuvant chemotherapy, radiotherapy).
4. Tumor-related spinal cord compression or meningeal metastasis.
5. History of malignant tumor within 2 years (except for basal cell carcinoma of the skin or cervical cancer in situ that has been adequately treated; other tumors that have been tumor-free for more than 2 years and are expected to survive for more than 2 years, which needs to be discussed with Dizal clinical research physicians).
6. Presence of severe or uncontrollable systemic diseases, including poorly controlled hypertension, bleeding diseases.
7. Presence of persistent or active infections, including but not limited to hepatitis B, hepatitis C and human immunodeficiency virus infection (HIV).
8. Any of the following heart-related diseases or abnormalities:

   * QT interval (QTc) \>470 msec after calibration of 12-lead ECG at rest during the screening period.
   * Any serious abnormalities of heart rate, conduction or pattern shown on the ECG at rest, such as complete left bundle branch block, third degree heart block, second degree heart block, PR interval \>250 msec.
   * Any disease or condition that can cause QTcF prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or family members with a history of sudden death under the age of 40.
   * Severe cardiovascular diseases such as myocardial infarction, unstable angina or congestive heart failure, cerebrovascular accident (such as history of stroke or intracranial hemorrhage) within 6 months before the first dose.
   * History of deep vein thrombosis or pulmonary embolism within 4 weeks before the first dose (excluding non-obstructive catheter-related thrombosis).
9. Patient history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid hormone treatment, or any clinically active ILD, immunotherapy-related pneumonitis.
10. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing medication, or previous intestinal resection that prevents adequate absorption of study medication.
11. Live vaccine within 4 weeks before the first dose.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Lu — Shanghai Chest Hospital
• Study coordinator: Yuanli Dong

Conditions Non Small Cell Lung Cancer