A First-In-human Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of Obrixtamig (BI 764532) Administered by Parenteral Route in Patients With Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3
概览
- 阶段
- 1 期
- 干预措施
- Obrixtamig - parenteral 2
- 疾病 / 适应症
- Patients With Small Cell Lung Carcinoma and Other Neoplasms
- 发起方
- Boehringer Ingelheim
- 入组人数
- 300
- 试验地点
- 24
- 主要终点
- Arm 1 and Arm 2: Maximum tolerated dose (MTD)
- 状态
- 招募中
- 最后更新
- 昨天
概览
简要总结
This study is open to adults with small cell lung cancer and other neuroendocrine cancers that are positive for the tumour marker delta-like 3 (DLL3). The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists.
The purpose of this study is to find out the highest dose of obrixtamig and the best treatment schedule that people can tolerate. Obrixtamig is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. In this study, obrixtamig is given to people for the first time. Interim clinical data are available for obrixtamig.
Participants get obrixtamig either weekly or once every 3 weeks. If there is benefit for the participants and if they can tolerate it, the treatment is given for a maximum of 3 years. During this time, participants visit the study site about 20 times depending on the response to the treatment. Doctors record any unwanted effects and regularly check the general health of the participants.
研究者
入排标准
入选标准
- •Signed and dated, written informed consent form (ICF2, ICF3 or ICF4) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses.
- •Locally advanced or metastatic cancer not amenable to curative treatment; of following histologies:
- •Small cell lung carcinoma (SCLC)
- •Large cells neuroendocrine lung carcinoma (LCNEC)
- •Neuroendocrine carcinoma (NEC) or small cell carcinoma of any other origin
- •Tumours must be positive for DLL3 expression (on archived tissue or instudy fresh biopsy) according to central pathology review in order to start obrixtamig
- •Patients with tumours with mixed histologies for any above type are eligible only if neuroendocrine carcinoma/small tumor cells component is predominant and represent at least 50% of the overall tumour tissue.
- •For back-fill cohorts only: patient has agreed to and signed an IC to provide mandatory pre-treatment and on-treatment fresh tumor biopsy.
- •Patient has failed or is not eligible for available standard therapies according to local guidelines. Standard therapies should include at least one line of chemotherapy that should include platinum for patients with small cells carcinoma tumors histologies.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
排除标准
- •Previous treatment with T cell Engager (TcE) or cell therapies targeting DLL
- •Other DLL3 targeting agents (like Rovalpituzumab tesirine (RovaT)) are allowed only if DLL3 positivity is documented after completion of treatment with DLL3 targeting agent in post-treatment biopsy.
- •Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed (e.g. biopsy).
- •Persistent toxicity from previous treatments that has not resolved to = Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, CTCAE Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by replacement therapy).
- •Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of obrixtamig. Physiological replacement of steroids is allowed.
- •Prior anti-cancer therapy:
- •Patients who have been treated with any other anti-cancer drug within 3 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of obrixtamig.
- •Patients who have been treated with extensive field radiotherapy including whole brain irradiation within 2 weeks prior to first administration of obrixtamig.
- •Other active malignancy that could interfere with the prognosis and treatment of the disease of the study.
- •Major surgery within 28 days of first dose obrixtamig.
研究组 & 干预措施
Arm 2: Obrixtamig
干预措施: Obrixtamig - parenteral 2
Arm 1: Obrixtamig
干预措施: Obrixtamig - parenteral 1
结局指标
主要结局
Arm 1 and Arm 2: Maximum tolerated dose (MTD)
时间窗: up to 36 months
Maximum tolerated dose (MTD) in any studied regimen defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal or above 33% during the MTD evaluation period. Separate MTDs will be determined for each Regimen.
Arm 1 and Arm 2: Number of patients with DLTs in the MTD evaluation period
时间窗: up to 36 months
次要结局
- Arm 1 and Arm 2: Area under the concentration-time curve (AUCτ) of the analyte over a uniform dosing interval τ(up to 36 months)
- Arm 1 and Arm 2: Maximum measured concentration (Cmax) of BI 764532(up to 36 months)
- Arm 1 and Arm 2: Objective response based on RECIST 1.1 criteria in patients with measurable disease(up to 36 months)
- Arm 1 and Arm 2: Maximum measured concentration (Cmax) of obrixtamig(up to 36 months)