Beamion BCGC-1: A Phase Ib dose escalation and Phase II dose optimization, randomized, open-label, multicenter trial of oral zongertinib (BI 1810631) alone or in combination with other agents for the treatment of patients with advanced HER2+metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 146
- 试验地点
- 27
- 主要终点
- Dose escalation (Phase Ib) Occurrence of DLTs in the MTD evaluation period. The MTD evaluation period is defined as the first 21 days of the first treatment cycle
研究概览
简要总结
Dose escalation (Phase Ib)
• To characterize the safety, tolerability, and the dose-toxicity curve of zongertinib: o in combination with T-DM1 in patients with HER2+ mBC (Cohort A) o in combination with T-DXd in patients with HER2+ mBC (Cohort B) o in combination with T-DXd in patients with mGEAC (Cohort C) o in combination with capecitabine and trastuzumab in patients with HER2+ mBC (Cohort G) o in combination with trastuzumab in patients with HER2+ mBC (Cohort K) by assessing escalating dose levels with overdose control to achieve primary objective of determining maximum tolerated doses (MTDs) and/or doses for further development per cohort
• To evaluate number of patients with "redacted as CCI" within MTD evaluation period per dose level. The MTD evaluation period is defined as the first 21 days of the first treatment cycle. The MTD is to be determined by dose escalation committee (DEC) based on the totality of data. It may be chosen as the highest dose with less than 25% risk of the true DLT rate being equal to or above 33% during MTD evaluation period based on the Bayesian Logistic Regression Model (BLRM) with overdose control (escalation with overdose control [EWOC]) for the trial
• The primary characterization of primary objective will be based on initial dose administered to patient during the MTD evaluation period and the strategy for handling intercurrent events will be a combined composite and principal stratum approach where some intercurrent events are considered as outcome and some define population consisting of patients who are able to adhere to the assigned treatment regimen and trial schedule
Dose optimization (Phase II)
• To assess anti-tumor activity of zongertinib in the following settings to assist in selection of optimal dose for further clinical development: o in combination with T-DM1 in patients with HER2+ mBC (Cohort D) o in combination with T-DXd in patients with HER2+ mBC (Cohort E) o in combination with T-DXd in patients with HER2+ mGEAC (Cohort F) o in combination with capecitabine and trastuzumab in patients with HER2+ mBC (Cohort H) o as a monotherapy in patients with HER2+ mBC (Cohort I, I-ext) o in combination with trastuzumab in patients with HER2+ mBC (Cohort J, J-ext)
• The primary endpoint is proportion of patients with objective response (OR) by RECIST version 1.1 as assessed by investigator review in the intent-to-treat population
• The summary measure of OR will include all treated patients regardless of breaks from trial treatment but will exclude the effects of any subsequent anti-cancer therapy started before progression
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF)
- •Documented HER2+ mBC or mGEAC
- •For dose optimization (Phase II): Patient must provide tumor tissue from locations not radiated prior to biopsy, if possible, collected through archival tissue
- •Documented investigator assessed progression
- •Presence of at least one measurable lesion according to RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
- •Adequate organ function based on laboratory values
排除标准
- •Mean resting corrected QT interval (QTcF) >470 msec.
- •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, personal or family history of long QT syndrome or unexplained sudden death under 40 years-of-age
- •Ejection fraction <50% or the lower limit of normal of the institutional standard within 28 days prior to randomization
- •History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
结局指标
主要结局
Dose escalation (Phase Ib) Occurrence of DLTs in the MTD evaluation period. The MTD evaluation period is defined as the first 21 days of the first treatment cycle
Dose escalation (Phase Ib) Occurrence of DLTs in the MTD evaluation period. The MTD evaluation period is defined as the first 21 days of the first treatment cycle
Dose optimization (Phase II) Objective response (OR) defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, or treatment discontinuation as assessed by investigator review
Dose optimization (Phase II) Objective response (OR) defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, or treatment discontinuation as assessed by investigator review
次要结局
- Dose escalation (Phase Ib) OR, as described above
- Occurrence of DLTs during the entire treatment period
- Intensive PK sampling: The following PK parameters of zongertinib when given in combination will be evaluated if feasible: o Cmax (SS): maximum measured concentration (at steady state) o AUC0-4h,ss : area under the concentration-time curve over the time interval from 0 to 4h at steady state o AUC0tz,ss: area under the concentration-time curve over the time interval from 0 to the last quantifiable data point at steady state
- Dose optimization (Phase II) o Progression-free survival (PFS), defined as the time from treatment start until the earliest date of tumor progression according RECIST 1.1 based on investigator review or death from any cause, whichever occurs first
- Disease control (DC) defined as best overall response of CR or PR or stable disease (SD) where best overall response is defined according to RECIST 1.1 from first treatment administration until the earliest of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, or treatment discontinuation, as assessed by investigator review
- Occurrence of treatment-emergent AEs (TEAEs) "redacted for CCI"
- Sparse PK sampling: The following PK parameters of zongertinib 1 when given as monotherapy or in combination will be evaluated if feasible: o Cmax (ss): maximum measured concentration (at steady state) o AUC0 tz, ss: area under the concentration-time curve over the time interval from 0 to the last quantifiable data point at steady state
- PROs: PRO-CTCAE (Mouth/throat sores, Taste changes, Decreased appetite, Nausea, Vomiting, Constipation, Diarrhoea, Shortness of breath, Cough, Rash, Skin dryness, Hair loss, Itching, Numbness & Tingling, Fatigue, Nosebleed, Headache); EORTC IL46 (1 item, overall side effect impact); EORTC IL19 (5 items, physical functioning scale of EORTC QLQ-C30). The time frame is from first administration until an individual patient’s end of treatment (EOT).
研究者
CT Disclosure & Data Transparency
Scientific
Boehringer Ingelheim International GmbH