A Phase III, Randomized, Multi-site, Open-label Trial of BNT323/DB-1303 Versus Investigator's Choice of Chemotherapy in Previously Treated Patients With HER2- Expressing Recurrent Endometrial Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- BioNTech SE
- 入组人数
- 480
- 试验地点
- 205
- 主要终点
- Cohort 1: PFS assessed by blinded independent central review (BICR) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
研究概览
简要总结
The study is divided into two cohorts (Cohort 1 and Cohort 2), to which participants will be enrolled based on the amount of human epidermal growth factor receptor 2 (HER2) in their tumor sample.
In Cohort 1, the main goal is to assess how well BNT323 (also known as DB-1303) or chemotherapy (doxorubicin or paclitaxel [or docetaxel, if participants cannot take paclitaxel]) works by determining the progression-free survival (PFS) of participants who have been previously treated with immune checkpoint inhibitors (ICIs).
In Cohort 2, the main goal is to assess how well BNT323 works by determining the objective response rate (ORR), that is, the percentage of participants whose tumor shrinks (partial response) or disappears (complete response) after treatment.
The safety of BNT323 will also be assessed by following the occurrence of unfavorable/adverse effects that are seen after treatment. Other measures include the pharmacokinetics of BNT323 (or how BNT323 moves through and out of the body), the body's immune response, and the impact on quality of life.
详细描述
This is an open-label, randomized, multi-site, Phase III, interventional clinical study designed to determine the efficacy and safety of BNT323 compared with investigator's choice of single agent chemotherapy in previously treated participants with recurrent endometrial cancer (including HER2 1+ or 2+ score as determined using a centralized immunohistochemistry [IHC] analysis method), whose disease has progressed on at least one line of platinum-based therapy and ICI (Cohort 1). In addition, participants with recurrent endometrial cancer with HER2 IHC 3+ score will be enrolled in a BNT323 monotherapy arm (Cohort 2) to further investigate the efficacy and safety of BNT323.
In Cohort 1, participants will be randomized 2:1 to receive either BNT323/DB-1303 or investigator's choice of single agent chemotherapy, preferably doxorubicin or paclitaxel (or docetaxel if contraindicated to paclitaxel and available at the site) until Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) defined progressive disease (PD) unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.
In Cohort 2, participants will receive BNT323 monotherapy until RECIST v1.1 defined PD unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.
The study consists of a screening period, a treatment period, a safety follow-up period, an efficacy follow-up period, and a long-term survival follow-up. The expected treatment duration per participant is ~6 months, followed by an anticipated long-term survival follow-up period of up to 53 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Are female adults (defined as ≥18 years of age or acceptable age according to local regulations at the time of voluntarily giving informed consent).
- •Have histologically confirmed endometrial cancer that:
- •Is recurrent,
- •Has a HER2 IHC score of 1+, 2+ (Cohort 1), or 3+ (Cohort 2) as determined by central laboratory testing for HER2 expression, and
- •Is not defined as a true sarcoma (i.e., leiomyosarcoma or endometrial stromal sarcoma). Note: Uterine carcinosarcoma is allowed.
- •Have measurable disease defined by RECIST v1.
- •Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or
- •Have recurrent endometrial cancer and meet any of the following:
- •developed recurrence <12 months from completing platinum-based chemotherapy given as adjuvant therapy for Stage I to III disease, or
- •developed recurrence after platinum-based chemotherapy in the recurrent/metastatic setting.
- •Have received prior ICI treatment (i.e., anti-programmed death 1/anti-programmed death-ligand 1)
- •Have a life expectancy of ≥12 weeks at screening.
排除标准
- •Are ineligible for all options in the investigator's choice of chemotherapy arm, per local prescribing information and institutional guidelines (applicable to Cohort 1 only).
- •Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior the first dose of study treatment.
- •Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
- •Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, or peritoneal shunt within 2 weeks prior to the first dose of study treatment.
- •Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Participants with prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses of less than 10 mg/day of prednisone or equivalent, and topical corticosteroids. Participants receiving corticosteroids may continue if the dose is stable upon giving main informed consent.
- •Have a lung-specific intercurrent clinically significant illness including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months prior to the first dose of study treatment, severe asthma, chronic obstructive pulmonary disorder with moderate acute exacerbations, restrictive lung disease, pulmonary fibrosis, radiation pneumonitis, significant pleural effusion etc.), or any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), and/or prior pneumonectomy (complete).
- •Have uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to the first dose of study treatment.
- •Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia, fatigue, or endocrinopathies that are well controlled) not yet resolved to Grade ≤1 or baseline.
- •Are pregnant or breastfeeding or are planning pregnancy during the study or within 7 months after the last dose of study treatment.
- •Have a history of allergies, hypersensitivities, or intolerance to study treatments (investigational medicinal products and auxiliary medicinal product) including any excipients thereof or to other monoclonal antibodies. Participants who have successfully undergone a desensitization process and are able to tolerate the drug are eligible.
- •Had prior treatment with topoisomerase I inhibitors, including ADCs.
- •Have left ventricular ejection fraction <55% by either echocardiography or multiple-gated acquisition within 28 days prior to the first dose of study treatment. This includes participants with tissue doppler E/e' ratio >
- •NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Cohort 1 - Doxorubicin or paclitaxel (or docetaxel)
Single agent chemotherapy (either doxorubicin or paclitaxel) per investigator's choice. Participants with contraindications to paclitaxel may receive docetaxel as an alternative (if available at the site).
干预措施: Doxorubicin (Drug)
Cohort 1 (HER2 IHC score 1+ or 2+): BNT323/DB-1303
干预措施: BNT323/DB-1303 (Drug)
Cohort 1 - Doxorubicin or paclitaxel (or docetaxel)
Single agent chemotherapy (either doxorubicin or paclitaxel) per investigator's choice. Participants with contraindications to paclitaxel may receive docetaxel as an alternative (if available at the site).
干预措施: Docetaxel (Drug)
Cohort 2 (HER2 IHC score 3+) - BNT323/DB-1303
干预措施: BNT323/DB-1303 (Drug)
Cohort 1 - Doxorubicin or paclitaxel (or docetaxel)
Single agent chemotherapy (either doxorubicin or paclitaxel) per investigator's choice. Participants with contraindications to paclitaxel may receive docetaxel as an alternative (if available at the site).
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Cohort 1: PFS assessed by blinded independent central review (BICR) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer
时间窗: Up to approximately 53 months
By treatment arm. Defined as the time from randomization to the first objective tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.
Cohort 2: ORR assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer
时间窗: Up to approximately 53 months
Defined as the proportion of participants with a CR or PR (per RECIST v1.1) as best overall response with confirmation.
次要结局
- Cohort 1: Overall survival (OS) in participants with HER2 IHC 1+/2+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 1: PFS assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 1: ORR assessed by BICR in participants with HER2 IHC 1+/2+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 1: ORR assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 1: Duration of response (DoR) assessed by BICR in participants with HER2 IHC 1+/2+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 1: DoR assessed by the investigator in participants with HER2 IHC 1+/2+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 1: Percentage of participants with HER2 IHC 1+/2+ recurrent endometrial cancer with occurrence of treatment-emergent adverse events (TEAEs)(Up to 35 days after the last dose of study treatment)
- Cohort 1: Percentage of participants with HER2 IHC 1+/2+ recurrent endometrial cancer with occurrence of TEAEs leading to drug interruption, dose reduction, or discontinuation of study treatment.(Up to 35 days after the last dose of study treatment)
- Cohort 2: ORR assessed by the investigator participants with HER2 IHC 3+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 2: DoR assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 2: DoR assessed by the investigator in participants with HER2 IHC 3+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 2: PFS assessed by BICR in participants with HER2 IHC 3+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 2: PFS assessed by the investigator in participants with HER2 IHC 3+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 2: OS in participants with HER2 IHC 3+ recurrent endometrial cancer(Up to approximately 53 months)
- Cohort 2: Percentage of participants with HER2 IHC 3+ recurrent endometrial cancer with occurrence of TEAEs(Up to 35 days after the last dose of study treatment)
- Cohort 2: Percentage of participants with HER2 IHC 3+ recurrent endometrial cancer with occurrence of TEAEs leading to drug interruption, dose reduction, or discontinuation of study treatment.(Up to 35 days after the last dose of study treatment)