Oral EGFR inhibitor DZD6008 (sunvozertinib) for advanced EGFR‑mutant non‑small cell lung cancer

A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Efficacy of DZD6008 in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations (TIAN-SHAN1)

This trial tests an oral EGFR inhibitor called DZD6008 (sunvozertinib) to see if it is safe and can shrink tumors in adults with advanced EGFR‑mutant non‑small cell lung cancer, including patients who have progressed after prior EGFR TKIs or who are treatment‑naïve.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Dizal Pharmaceuticals (Industry-sponsored)
• Drugs / interventions: sunvozertinib, chemotherapy, Immunotherapy, radiation
• Locations: 5 sites (New York, New York and 4 other locations)
• Trial ID: NCT06905197 on ClinicalTrials.gov

What this trial studies

This Phase 1, multinational, interventional study gives oral DZD6008 to adults with locally advanced or metastatic non‑small cell lung cancer that harbors EGFR sensitizing mutations. Part A uses a dose‑escalation design to define safety and the recommended dose in patients who have failed at least one prior EGFR TKI, and Part B expands selected dose cohorts to study activity in patients previously treated with a third‑generation EGFR TKI and in treatment‑naïve patients. Key outcomes include safety, tolerability, pharmacokinetics, and anti‑tumor activity measured by objective response and progression; tumor tissue is required for mutation confirmation and correlative analyses. Sites in New York and Virginia will enroll patients and follow them with scheduled clinic visits, imaging, and laboratory monitoring.

Who should consider this trial

Good fit: Ideal candidates are adults with locally advanced or metastatic NSCLC harboring EGFR sensitizing mutations (Exon 19 deletion or L858R), ECOG 0–1, able to provide tumor tissue, and meeting the prior‑therapy criteria for the study part.

Not a fit: Patients without EGFR sensitizing mutations, with poor performance status (ECOG ≥2), uncontrolled brain metastases, or who cannot provide required tumor samples are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, DZD6008 could provide a new oral treatment option for patients with EGFR‑mutant NSCLC, including those with resistance to existing EGFR TKIs.

How similar studies have performed: Other EGFR inhibitors, including third‑generation agents like osimertinib, have shown clear benefit in EGFR‑mutant NSCLC, but resistance commonly develops and newer agents such as DZD6008 are novel and remain early in clinical testing.

Eligibility criteria

Inclusion Criteria:

1. Patients must be able to provide documented informed consent.
2. Aged ≥ 18 years.
3. Histologically or cytologically confirmed diagnosis of NSCLC, locally advanced or metastatic, not suitable for curative therapy.
4. Documentation of EGFR mutations from a local CLIA-certified laboratory (or equivalent). For Part A monotherapy cohorts and all cohorts of Part B, EGFR sensitizing mutations (Exon19del and/or L858R) are required.
5. Provide adequate amount of pretreatment tumor samples collected after disease progression on the last EGFR TKI treatment. (previously treated patients) or before study treatment (treatment naïve patients).
6. Part A: Failed (progressed or are intolerant) from at least 1 prior EGFR TKI regimen. Cohort A of Part B: Failed 1 prior third-generation EGFR TKI regimen. Cohorts B of Part B: Patients who are treatment naïve.
7. ECOG 0 or 1 with predicted life expectancy ≥ 12 weeks.
8. Patients with brain metastases must have a stable BM status.
9. Measurable disease per RECIST 1.1.
10. Adequate hematopoietic and other organ system functions.
11. Male Patients with female partners of childbearing potential should use barrier contraceptives and refrain from donating sperm during their participation in this study and for 3 months following the last dose of the study drug.

Exclusion Criteria:

1. Carry other EGFR alterations than T790M and C797X, including but not limited to uncommon EGFR mutations (G719X, S768I, L861Q, exon 20 insertions mutations, etc.)(Part B).
2. NSCLC with mixed small cell lung cancer (SCLC) or NSCLC with histologic SCLC transformation.
3. Prior treatment with any of the following: 1)Immunotherapy or other antibody therapy within 4 weeks prior to the first administration; 2)Any cytotoxic chemotherapy, investigational drugs or other anticancer drugs from a previous treatment regimen or clinical study within 14 days prior to the first administration; 3)Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose, radiation to more than 30% of the bone marrow or with a wide field of radiation within 28 days before screening; 4)Currently receiving or unable to stop drug or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP)3A4. A washout period of at least 2 weeks for strong inhibitors and 3 weeks for strong inducers is required prior to the first study drug administration; 5)currently receiving or unable to stop drugs known to be CYP3A4 sensitive substrate with a narrow therapeutic index. A washout period of at least 14 days is required prior to the first study drug administration; 6)currently receiving or unable to stop drugs known to be proton pump inhibitors. A washout period of at least 7 days is required prior to the first study drug administration; 7)major surgery within 4 weeks of the first administration of DZD6008 or anticipated during the study period.
4. Any unresolved toxicities from prior anti-cancer therapy greater than CTCAE Grade 1.
5. Spinal cord compression or leptomeningeal metastasis.
6. Patients with any other malignancy within 2 years of the first administration of study drug.
7. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses as judged by investigator.
8. Patients with active infection, including but not limited to HBV, HCV, HIV and active infection of COVID-19.
9. Resting QTcF \> 470 msec; Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG;Any factors that increase the risk of QTc prolongation.
10. Past medical history of ILD or active ILD.
11. Diseases which would preclude adequate absorption of DZD6008.
12. Received a live vaccine within 2 weeks before the first administration of DZD6008.
13. Women who are pregnant or breastfeeding.
14. Hypersensitivity to active or inactive excipients of DZD6008 or sunvozertinib.
15. Involvement in the planning and conduct of the study.
16. Judgment by the investigator that the patient is unlikely to comply with study procedures

Where this trial is running

New York, New York and 4 other locations

• Laura and Isaac Perlmutter Cancer Center at NYU Langone Health — New York, New York, United States (Recruiting)
• Herbert Irving Comprehensive Cancer Center — New York, New York, United States (Recruiting)
• Virginia Cancer Specialist (NEXT Oncology-Virginia) — Fairfax, Virginia, United States (Active_not_recruiting)
• Blacktown Hospital — Blacktown, New South Wales, Australia (Active_not_recruiting)
• Chris O'Brien Lifehouse — Camperdown, New South Wales, Australia (Not_yet_recruiting)

Study contacts

• Study coordinator: Yifan Liu

Conditions Non Small Cell Lung Cancer