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

NCT06905197 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DZ2023C0001
• Study Type: interventional
• Target: 140
• Locations: 2 countries
• Sites: 5

Brief Summary

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

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (9)

• Part A: To characterize the plasma concentration of DZD6008 following single and multiple oral dose administration

  From first dosing to cycle 7 day 1, each cycle is 21 days

• Part A: To characterize the plasma concentration of sunvozertinib and metabolite DZ0753 following single and multiple oral dose administration

  From first dosing to cycle 9 day 1, each cycle is 21 days

• Part A: To assess the anti-tumor activity

  Through the study completion, an average of around 1 year

• Part A: To assess the anti-tumor activity

  Through the study completion, an average of around 1 year

• Part A: To assess the anti-tumor activity

  Through the study completion, an average of around 1 year

Study Arms (13)

Experimental: Part A Dose Escalation monotherapy cohorts (20 mg once daily [QD])

EXPERIMENTAL

Drug: DZD6008

Experimental: Part A Dose Escalation monotherapy cohorts (40 mg QD)

EXPERIMENTAL

Drug: DZD6008

Experimental: Part A Dose Escalation monotherapy cohorts (60 mg QD)

EXPERIMENTAL

Drug: DZD6008

Experimental: Part A Dose Escalation monotherapy cohorts (90 mg QD)

EXPERIMENTAL

Drug: DZD6008

Experimental: Part A Dose Escalation monotherapy cohorts (120 mg QD)

EXPERIMENTAL

Drug: DZD6008

Experimental: Part A Dose Escalation monotherapy cohorts (150 mg QD)

EXPERIMENTAL

Drug: DZD6008

Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 1)

EXPERIMENTAL

Drug: DZD6008; Drug: Sunvozertinib

Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 2)

EXPERIMENTAL

Drug: DZD6008; Drug: Sunvozertinib

Experimental: Part A Dose Escalation Combination cohorts (Combination dose 3)

EXPERIMENTAL

Drug: DZD6008; Drug: Sunvozertinib

Experimental: Part B Dose Expansion cohort A1 (selected dose 1)

EXPERIMENTAL

Drug: DZD6008

Experimental: Experimental: Part B Dose Expansion cohort A2 (selected dose 2)

EXPERIMENTAL

Drug: DZD6008

Experimental: Experimental: Part B Dose Expansion cohort B1 (selected dose 1)

EXPERIMENTAL

Drug: DZD6008

Experimental: Experimental: Part B Dose Expansion cohort B2 (selected dose 2)

EXPERIMENTAL

Drug: DZD6008

Interventions

DZD6008 DRUG

Daily dose of DZD6008

Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 1); Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 2); Experimental: Experimental: Part B Dose Expansion cohort A2 (selected dose 2); Experimental: Experimental: Part B Dose Expansion cohort B1 (selected dose 1); Experimental: Experimental: Part B Dose Expansion cohort B2 (selected dose 2); Experimental: Part A Dose Escalation Combination cohorts (Combination dose 3); Experimental: Part A Dose Escalation monotherapy cohorts (120 mg QD); Experimental: Part A Dose Escalation monotherapy cohorts (150 mg QD); Experimental: Part A Dose Escalation monotherapy cohorts (20 mg once daily [QD]); Experimental: Part A Dose Escalation monotherapy cohorts (40 mg QD); Experimental: Part A Dose Escalation monotherapy cohorts (60 mg QD); Experimental: Part A Dose Escalation monotherapy cohorts (90 mg QD); Experimental: Part B Dose Expansion cohort A1 (selected dose 1)

Sunvozertinib DRUG

Daily dose of Sunvozertinib

Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 1); Experimental: Experimental: Part A Dose Escalation Combination cohorts (Combination dose 2); Experimental: Part A Dose Escalation Combination cohorts (Combination dose 3)

Eligibility Criteria

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

You may qualify if:

• Patients must be able to provide documented informed consent.
• Aged ≥ 18 years.
• Histologically or cytologically confirmed diagnosis of NSCLC, locally advanced or metastatic, not suitable for curative therapy.
• 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.
• 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).
• 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.
• ECOG 0 or 1 with predicted life expectancy ≥ 12 weeks.
• Patients with brain metastases must have a stable BM status.
• Measurable disease per RECIST 1.1.
• Adequate hematopoietic and other organ system functions.
• 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.

You may not qualify if:

• 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).
• NSCLC with mixed small cell lung cancer (SCLC) or NSCLC with histologic SCLC transformation.
• 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.
• Any unresolved toxicities from prior anti-cancer therapy greater than CTCAE Grade 1.
• Spinal cord compression or leptomeningeal metastasis.
• Patients with any other malignancy within 2 years of the first administration of study drug.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses as judged by investigator.
• Patients with active infection, including but not limited to HBV, HCV, HIV and active infection of COVID-19.
• 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.
• Past medical history of ILD or active ILD.
• Diseases which would preclude adequate absorption of DZD6008.
• Received a live vaccine within 2 weeks before the first administration of DZD6008.
• Women who are pregnant or breastfeeding.
• Hypersensitivity to active or inactive excipients of DZD6008 or sunvozertinib.
• Involvement in the planning and conduct of the study.

Sponsors & Collaborators

• Dizal Pharmaceuticals: lead

Study Sites (5)

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

RECRUITING

Virginia Cancer Specialist (NEXT Oncology-Virginia)

Fairfax, Virginia, 22031, United States

ACTIVE NOT RECRUITING

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

ACTIVE NOT RECRUITING

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Yifan Liu

CONTACT

86-21-61095854; yifan.liu@dizalpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 1, 2025
• Study Start: May 13, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); AU (2)