Assessing an Oral EGFR Inhibitor, DZD6008 in Patients Who Have Advanced NSCLC With EGFR Mutations (TIAN-SHAN2)

NCT06813365 | Recruiting Phase 1

• 1 other identifier: DZ2023C0002
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate safety and antitumor activity of DZD6008 in patients with advanced NSCLC with EGFR mutations. This is the first time the drug is tested in human.

Conditions

Nonsmall-cell Lung Cancer

Keywords

Lung Cancer, EGFR mutation

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) as 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 (12)

• 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 assess the urine concentration of DZD6008

  At the first day of cycle 2 (each cycle is 21 days).

• Part A: To assess cerebrospinal fluid of DZD6008 in participants with brain metastasis at baseline

  Cycle 1 day 15.

• Part A: To assess the effect of low-fat food on the plasma concentration of DZD6008

  The first dosing day on cycle 0 (cycle 0 is 3 days).

• Part A: To assess the anti-tumor activity

  Through the study completion, an average of around 1 year.

Study Arms (10)

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

EXPERIMENTAL

Drug: DZD6008

Part A Dose Escalation cohorts (40 mg QD)

EXPERIMENTAL

Drug: DZD6008

Part A Dose Escalation cohorts (60 mg QD)

EXPERIMENTAL

Drug: DZD6008

Part A Dose Escalation cohorts (90 mg QD)

EXPERIMENTAL

Drug: DZD6008

Part A Dose Escalation cohorts (120 mg QD)

EXPERIMENTAL

Drug: DZD6008

Part A Dose Escalation cohorts (150 mg QD)

EXPERIMENTAL

Drug: DZD6008

Part B Dose Expansion cohorts (selected dose 1 QD)

EXPERIMENTAL

Drug: DZD6008

Part B Dose Expansion cohorts (selected dose 2 QD)

EXPERIMENTAL

Drug: DZD6008

Food effect cohort (selected dose 1)

EXPERIMENTAL

Drug: DZD6008

Food effect cohort (selected dose 2)

EXPERIMENTAL

Drug: DZD6008

Interventions

DZD6008 DRUG

Daily dose of DZD6008

Food effect cohort (selected dose 1); Food effect cohort (selected dose 2); Part A Dose Escalation cohorts (120 mg QD); Part A Dose Escalation cohorts (150 mg QD); Part A Dose Escalation cohorts (20 mg once daily [QD]); Part A Dose Escalation cohorts (40 mg QD); Part A Dose Escalation cohorts (60 mg QD); Part A Dose Escalation cohorts (90 mg QD); Part B Dose Expansion cohorts (selected dose 1 QD); Part B Dose Expansion cohorts (selected dose 2 QD)

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 sensitizing mutation (Exon19del and/or L858R) from a local CLIA-certified laboratory (or equivalent).
• Provide adequate amount of pretreatment tumor samples for retrospective confirmation of EGFR mutations by the central laboratory.
• Part A: Failed (progressed or are intolerant) at least 1 prior EGFR TKI and platinum-based chemotherapy. Part B: Cohorts 1 and 2: Failed 1 prior third-generation EGFR TKI. Cohorts 3 and 4: Patients who are treatment naïve.
• Note: Patients enrolled in the study should be representative of the population to meet the need for efficacy analysis in the population after TKI failure (e.g., including appropriate proportion and number of patients with the C797X mutation if possible)
• 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 any other known EGFR alterations, including but not limited to uncommon EGFR mutations (G719X, S768I, L861Q, exon 20 insertions, 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.
• Women who are pregnant or breastfeeding.
• Hypersensitivity to active or inactive excipients of DZD6008.
• Involvement in the planning and conduct of the study.
• Judgment by the investigator that the patients is unlikely to comply with study procedures

Sponsors & Collaborators

• Dizal Pharmaceuticals: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100005, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Hui Wang

CONTACT

86-21-61098347; Hui.Wang02@dizalpharma.com

Study Design

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

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: February 6, 2025
• Study Start: June 12, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): July 30, 2028
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

CN (1)