A Study of ZL-1310 in Subjects With Small Cell Lung Cancer

Официальное название

An Open-label, Multicenter Study of ZL-1310 to Evaluate the Safety, Efficacy, and Pharmacokinetics in Participants With Small Cell Lung Cancer

Обзор

An open-label, multicenter study of ZL-1310 as a single agent and in combination with Atezolizumab (with and without Carboplatin) to evaluate the safety, efficacy, and pharmacokinetics in subjects with small cell lung cancer

Подробное описание

This is an open-label, ascending, multiple-dose, phase 1 study evaluating ZL-1310 as a single agent, in combination with Atezolizumab, and in combination with Atezolizumab and Carboplatin in subjects with extensive SCLC.

Вмешательства

• Препарат ZL-1310
  Drug: ZL-1310
• Препарат Atezolizumab
  Drug Atezolizumab
• Препарат Carboplatin
  Drug Carboplatin

Первичные конечные точки

• Incidence of Dose Limiting Toxicities of ZL-1310 as a single agent (Part 1A), in combination with Atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C) [Срок оценки: up to 24 months]
• Incidence of Treatment Emergent Adverse-Events of ZL-1310 as a single agent (Part 1A), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C) [Срок оценки: up to 24 months]
• Incidence of Serious Adverse Events of ZL-1310 as a single agent (Part 1A), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C) [Срок оценки: up to 24 months]
• Incidence of Treatment Emergent Adverse Events of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3) and in combination with atezolizumab and carboplatin (Part 4) [Срок оценки: up to 24 months]
• Incidence of Serious Adverse-Events (SAEs) of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3), and in combination with atezolizumab and carboplatin (Part 4) [Срок оценки: up to 24 months]
• Antitumor activity per RECIST v1.1 by investigator's assessment of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3), and in combination with atezolizumab and carboplatin (Part 4) [Срок оценки: up to 24 months]
• Objective response rate (ORR) per RECIST v1.1 of ZL-1310 as a single agent (Part 2) and in combination with atezolizumab and carboplatin (Part 4) [Срок оценки: up to 24 months]
• Disease control rate (DCR) per RECIST v1.1 of ZL-1310 in combination with atezolizumab [Срок оценки: up to 24 months]

Вторичные конечные точки (7)

• Objective response rate (ORR) per RECIST 1.1 of ZL-1310 as a single agent (Part 1A) in combination with atezolizumab (Part 1B), in combination with atezolizumab and carboplatin (Part 1C, Part 3) [Срок оценки: up to 24 months]
• Disease control rate (DCR) per RECIST v1.1 of ZL-1310 as a single agent (Part 1A and Part 2), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 4) [Срок оценки: up to 24 months]
• Duration of response per RECIST v1.1 [Срок оценки: up to 24 months]
• Progression free survival per RECIST v1.1 [Срок оценки: up to 24 months]
• Overall Survival of ZL-1310 [Срок оценки: up to 24 months]
• Pharmacokinetics: Total Antibody of ZL-1310 [Срок оценки: up to 24 months]
• Pharmacokinetics: Unconjugated payloads of ZL-1310 [Срок оценки: up to 24 months]

Критерии участия

Критерии включения

• Signed informed consent
• Participant with metastatic or extensive-stage small cell lung cancer (de novo, not transformed) and for Part 1A and 1B must have documented disease progression during or following a platinum-based chemotherapy regimen. For Part 1C and Part 4, no prior systemic treatment for SCLC (including chemoradiotherapy for limited-stage SCLC). For Part 1B backfill and Part 3, first-line setting: no prior systemic treatment for SCLC (including chemoradiotherapy for limited-stage SCLC); or, first-line maintenance setting: participants have received at least 4 cycles of 1L induction therapy with carboplatin or cisplatin, etoposide, and anti-PD-L1 inhibitor for ES-SCLC with ongoing CR, PR, or SD per RECIST v1.1 assessed by the investigator. For Part 2-1, participants must have received no more than 2 lines of prior therapies in the extensive-stage setting, and progressed on or after a platinum-based chemotherapy regimen AND an anti-DLL3 T-cell engager (TCE). For Part 3, participants have received at least 4 cycles of 1L induction therapy with carboplatin or cisplatin etoposide, and anti-PD-L1 inhibitor for ES-SCLC with ongoing CR, PR, or SD per RECIST v1.1 assessed by the investigator.
• Adult men and women ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subjects must have at least one measurable target lesion as defined by RECIST v1.1 on CT, PET/CT, or MRI.
• Subjects must be willing to undergo a tumor biopsy or must provide archived tumor tissue sample at screening per protocol guidelines.
• Life Expectancy >/= 3 months.

Критерии исключения

• Participants with another known malignancy that is progressing or requires active treatment within the last 2 years. Exceptions: basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin with previously administered curative treatment, in situ cervical cancer, or other cancers that do not require systemic anti-cancer therapies and will not impact life expectancy.
• Symptomatic or untreated brain metastasis requiring concurrent treatment. For Part 2, Part 3, and Part 4 the following subjects can be enrolled if they have a stable neurologic status for at least 2 weeks prior to the first dose of ZL-1310:

• Subjects with untreated and asymptomatic brain metastases.
• Subjects with treated brain metastases that are no longer symptomatic (i.e. without neurologic signs or symptoms), who require no treatment with steriods or anticonvulsants and have recovered from the actue toxic effects of radiotherapy.
• Subjects with leptomeningeal disease.
• Treatment with any systemic anti-cancer treatment or other investigational products/ device within 3 weeks before first dose of study treatment.
• Non-palliative radiotherapy within 2 weeks prior to first dose of study treatment or have had a history of radiation pneumonitis.
• Major surgery within 4 weeks of the first dose of study treatment.
• Hypersensitivity to any ingredient of the study treatment.
• Inadequate organ function (as defined in protocol) within 10 days prior to the first dose of study treatment,
• Participants with a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 14 days or 5 half-lives before the first dose of study treatment, whichever is longer.
• Participants have received a live or live-attenuated vaccine within 30 days of planned start of study therapy.
• Impaired cardiac function or clinically significant cardiac disease within the last 3 months before administration of the first dose of the study treatment
• Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue, or inflammatory disorders, including but not limited to pneumonitis.
• Pregnant or nursing (lactating) women.
• Participants who have been on concomitant strong CYP3A or CYP2D6 inhibitors within 14 days or 5 half-lives before the first study treatment, whichever is longer.
• For Part 1C and Part 4 (ZL-1310 in combination with Atezolizumab and Carboplatin), participants who received prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
• For Part 1B (ZL-1310 in combination with Atezolizumab) and Part 1C (ZL-1310 in combination with Atezolizumab and Carboplatin), participants who received systemic immunostimulatory agents (including but not limited to, IFNs and IL2) within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to the initiation of study treatment.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 16 центров

• Zai Lab Site 1004 — Хэфэй
• Zai Lab Site 1005 — Пекин
• Zai Lab Site 1012 — Xiamen
• Zai Lab Site 1001 — Гуанчжоу
• Zai Lab Site 1009 — Харбин
• Zai Lab Site 1006 — Чжэнчжоу
• Zai Lab 1002 — Ухань
• Zai Lab Site 1014 — Чанша
• … и ещё 8 центров

США · 11 центров

• Zai Lab Site 2005 — Duarte
• Zai Lab Site 2030 — New Haven
• Zai Lab Site 2026 — Sarasota
• Zai Lab Site 2013 — Detroit
• Zai Lab Site 2001 — Hackensack
• Zai Lab Site 2002 — Buffalo
• Zai Lab Site 2018 — Durham
• Zai Lab Site 2024 — Cleveland
• … и ещё 3 центра

Испания · 11 центров

• Zai Lab Site 8002 — Barcelona
• Zai Lab Site 8003 — Madrid
• Zai Lab Site 8006 — Madrid
• Zai Lab Site 8005 — Seville
• Zai Lab Site 8004 — Valencia
• Zai Lab Site 8001 — Valencia
• Zai Lab Site 8007 — Barcelona
• Zai Lab Site 8009 — Madrid
• … и ещё 3 центра

Идентификаторы

NCT: NCT06179069 · ZL-1310-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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