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

Официальное название

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)

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат DZD6008
  Daily dose of DZD6008
• Препарат Sunvozertinib
  Daily dose of Sunvozertinib

Первичные конечные точки

• Part A: To assess safety and tolerability [Срок оценки: 21 days after the first multiple dose]
• Part A: To assess safety and tolerability [Срок оценки: Through the study completion, an average of around 1 year]
• Part B: To assess anti-tumor activity [Срок оценки: Through the study completion, an average of around 1 year]

Вторичные конечные точки (9)

• Part A: To characterize the plasma concentration of DZD6008 following single and multiple oral dose administration [Срок оценки: 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 [Срок оценки: From first dosing to cycle 9 day 1, each cycle is 21 days]
• Part A: To assess the anti-tumor activity [Срок оценки: Through the study completion, an average of around 1 year]
• Part A: To assess the anti-tumor activity [Срок оценки: Through the study completion, an average of around 1 year]
• Part A: To assess the anti-tumor activity [Срок оценки: Through the study completion, an average of around 1 year]
• Part B: To assess the anti-tumor activity [Срок оценки: Through the study completion, an average of around 1 year]
• Part B: To assess the anti-tumor activity [Срок оценки: PFS assessed by investigators per RECIST version 1.1]
• Part B: Plasma concentration of DZD6008 [Срок оценки: Time Frame: From first dosing to cycle 11 day 1, each cycle is 21 days]
• Part B: To assess safety and tolerability [Срок оценки: Through the study completion, an average of around 1 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• Judgment by the investigator that the patient is unlikely to comply with study procedures

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Laura and Isaac Perlmutter Cancer Center at NYU Langone Health — New York
• Herbert Irving Comprehensive Cancer Center — New York
• Virginia Cancer Specialist (NEXT Oncology-Virginia) — Fairfax

Австралия · 2 центра

• Blacktown Hospital — Blacktown
• Chris O'Brien Lifehouse — Camperdown

Идентификаторы

NCT: NCT06905197 · DZ2023C0001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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