A Multinational Study Assessing an Oral EGFR Inhibitor, DZD6008 in Patients Who Have Advanced NSCLC With EGFR Mutations (TIAN-SHAN1)

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 study is designed to evaluate safety and anti-tumor activity of DZD6008 in patients with advanced NSCLC with EGFR mutations.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Sunvozertinib; Drug: DZD6008

Detailed Description

The study includes two parts: Part A (dose escalation) and Part B (dose expansion). In Part A, locally advanced or metastatic NSCLC patients with EGFR mutations following at least 1 prior EGFR TKI regimen will be enrolled. In Part B, locally advanced or metastatic NSCLC patients with EGFR sensitizing mutations, who are previously treated with 1 line of third-generation of EGFR TKI treatment as well as treatment naïve will be enrolled.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yifan Liu; Phone Number: 86-21-61095854; Email: yifan.liu@dizalpharma.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Active, not recruiting
      • Blacktown Hospital
    • Camperdown, New South Wales, Australia, 2050
      • Not yet recruiting
      • Chris O'Brien Lifehouse
      • Contact: Kao; Phone Number: 61-2- 85140000; Email: steven.kao@lh.org.au
• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Herbert Irving Comprehensive Cancer Center
      • Contact: Shu; Phone Number: (212) 305-3997; Email: cas2145@cumc.columbia.edu
    • New York, New York, United States, 10016
      • Recruiting
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
      • Contact: Shum; Phone Number: 1-347-978-5004; Email: elaine.shum@nyulangone.org
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Active, not recruiting
      • Virginia Cancer Specialist (NEXT Oncology-Virginia)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Part A Dose Escalation monotherapy cohorts (20 mg once daily [QD])	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Part A Dose Escalation monotherapy cohorts (40 mg QD)	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Part A Dose Escalation monotherapy cohorts (60 mg QD)	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Part A Dose Escalation monotherapy cohorts (90 mg QD)	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Part A Dose Escalation monotherapy cohorts (120 mg QD)	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Part A Dose Escalation monotherapy cohorts (150 mg QD)	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 1)	Drug: Sunvozertinib; Daily dose of Sunvozertinib; Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 2)	Drug: Sunvozertinib; Daily dose of Sunvozertinib; Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 3)	Drug: Sunvozertinib; Daily dose of Sunvozertinib; Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Part B Dose Expansion cohort A1 (selected dose 1)	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Experimental: Part B Dose Expansion cohort A2 (selected dose 2)	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Experimental: Part B Dose Expansion cohort B1 (selected dose 1)	Drug: DZD6008; Daily dose of DZD6008
Experimental: Experimental: Experimental: Part B Dose Expansion cohort B2 (selected dose 2)	Drug: DZD6008; Daily dose of DZD6008

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: To assess safety and tolerability	Number of participants with Dose-limiting Toxicities (DLTs)	21 days after the first multiple dose
Part A: To assess safety and tolerability	Number of participants with Adverse events (AEs)/Serious adverse events (SAEs)	Through the study completion, an average of around 1 year
Part B: To assess anti-tumor activity	Objective Response Rate (ORR) assessed by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Through the study completion, an average of around 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: To characterize the plasma concentration of DZD6008 following single and multiple oral dose administration	Total concentrations of DZD6008 in plasma	From first dosing to cycle 7 day 1, each cycle is 21 days
Part A: To assess the anti-tumor activity	ORR assessed by investigators per RECIST version 1.1	Through the study completion, an average of around 1 year
Part A: To assess the anti-tumor activity	Duration of Response (DoR) assessed by investigators per RECIST version 1.1	Through the study completion, an average of around 1 year
Part A: To assess the anti-tumor activity	Progression Free Survival (PFS) assessed by investigators per RECIST version 1.1	Through the study completion, an average of around 1 year
Part B: Plasma concentration of DZD6008	Total concentrations of DZD6008 in plasma	Time Frame: From first dosing to cycle 11 day 1, each cycle is 21 days
Part B: To assess safety and tolerability	Number of participants with AEs/SAEs	Through the study completion, an average of around 1 year
Part A: To characterize the plasma concentration of sunvozertinib and metabolite DZ0753 following single and multiple oral dose administration	Total concentrations of sunvozertinib and metabolite DZ0753 in plasma (combination cohorts only)	From first dosing to cycle 9 day 1, each cycle is 21 days
Part B: To assess the anti-tumor activity	DoR assessed by investigators per RECIST version 1.1	Through the study completion, an average of around 1 year
Part B: To assess the anti-tumor activity	Through the study completion, an average of around 1 year	PFS assessed by investigators per RECIST version 1.1

Collaborators and Investigators

• Sponsor: Dizal Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: March 25, 2025
• First Posted (Actual): April 1, 2025

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: DZ2023C0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No