A Phase III, Multisite, Randomized, Double-Blind Trial of BNT327 in Combination With Chemotherapy Versus Placebo With Chemotherapy in Patients With Previously Untreated Locally Recurrent Inoperable or Metastatic TNBC Determined Ineligible for PD(L)1 Therapy Based on PD-L1 Negative Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- BioNTech SE
- 入组人数
- 558
- 试验地点
- 203
- 主要终点
- Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
This is a Phase III trial where participants will be randomized to two treatment groups, which means participants will be assigned by equal chance to a treatment group. This trial will be double-blinded, which means neither the participants nor the trial doctors will know which of the two treatments the participants actually receive. Participants will receive either the trial drug with chemotherapy or placebo (which looks like the trial drug but does not have any drug in it) with chemotherapy.
详细描述
The study consists of a:
- Screening period (up to 28 days);
- Treatment period, during which participants will receive pumitamig or placebo in combination with chemotherapy (until disease progression, the occurrence of intolerable toxicity, withdrawal, death, or trial termination [whichever comes first]);
- Safety follow-up (FU) period (for up to 90 days after administration of the last dose of trial treatment) and survival follow-up (until the participant dies, withdraws consent for survival status follow-up, loss of contact, or sponsor decision, whichever occurs first).
Participants will be randomized 1:1 to receive either pumitamig in combination with the treatment of physician's choice (TPC) chemotherapy (Arm 1) or placebo in combination with TPC chemotherapy (Arm 2). Chemotherapy will be administered per standard of care. The randomization will be stratified based on the following factors:
- Prior treatment with cancer immunotherapy (yes versus no)
- On-trial chemotherapy regimen (paclitaxel/nab-paclitaxel versus gemcitabine plus carboplatin versus eribulin)
- Geography (East Asia versus the rest of the world [ROW])
- PD-L1 status (combined positive score [CPS] less than [<] 1 versus 1 less than or equal to [<=] CPS <10).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are considered ineligible for combination treatment with a monospecific PD(L)1 targeting immunotherapy plus chemotherapy as per their tumor PD-L1 expression status.
- •Have confirmed locally recurrent inoperable or metastatic TNBC, or estrogen receptor (ER)-low, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (ER and/or progesterone receptor [PgR]) 1% to 10%, HER2 immunohistochemistry [IHC] 0, 1+, or 2+ with fluorescence in situ hybridization [FISH] negative for HER2 gene amplification) documented prior to trial screening as part of standard of care.
- •Have at least one measurable lesion as the targeted lesion based on RECIST v1.
- •Have provided a tissue sample, archival or fresh, during the screening period (bone biopsies, fine needle aspiration biopsies, and samples from pleural or peritoneal fluid are not acceptable; participants with only one target lesion are not eligible to participate in the trial).
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1.
排除标准
- •Have received any of the following therapies or drugs prior to the initiation of trial:
- •Have received prior systemic anticancer therapy for advanced disease.
- •Have received prior treatment with a PD(L)-1/vascular endothelial growth factor (VEGF) bispecific antibody.
- •Have received systemic corticosteroids (at a dosage greater than 10 milligrams [mg]/day of prednisone or an equivalent dose of other corticosteroids) within 7 days prior to the initiation of trial treatment. Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (<= 7 days) of corticosteroids for prophylaxis (for example, prevention of contrast agent allergy) or treatment of non-autoimmune conditions (for example, delayed hypersensitivity reactions caused by exposure to allergens).
- •Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of trial treatment.
- •Have received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of trial treatment.
- •Are pregnant or breastfeeding or are planning pregnancy or planning to father children during the trial or within 6 months after the last dose of pumitamig or placebo.
- •Have undergone major organ surgery, significant trauma, or invasive dental procedures (such as dental implants) within 28 days prior to the initiation of trial treatment or plan to undergo elective surgery during the trial. Placement of vascular infusion devices is allowed.
- •Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
研究组 & 干预措施
Arm 2: Placebo + TPC Chemotherapy
Participants will be administered with matching placebo plus chemotherapy regimen.
干预措施: Nab-paclitaxel/Paclitaxel (Drug)
Arm 1: Pumitamig + Treatment of Physician's Choice (TPC) Chemotherapy
Participants will be administered with pumitamig (BNT327) plus chemotherapy regimen.
干预措施: Gemcitabine (Drug)
Arm 2: Placebo + TPC Chemotherapy
Participants will be administered with matching placebo plus chemotherapy regimen.
干预措施: Gemcitabine (Drug)
Arm 1: Pumitamig + Treatment of Physician's Choice (TPC) Chemotherapy
Participants will be administered with pumitamig (BNT327) plus chemotherapy regimen.
干预措施: Carboplatin (Drug)
Arm 2: Placebo + TPC Chemotherapy
Participants will be administered with matching placebo plus chemotherapy regimen.
干预措施: Eribulin (Drug)
Arm 1: Pumitamig + Treatment of Physician's Choice (TPC) Chemotherapy
Participants will be administered with pumitamig (BNT327) plus chemotherapy regimen.
干预措施: Pumitamig (Drug)
Arm 1: Pumitamig + Treatment of Physician's Choice (TPC) Chemotherapy
Participants will be administered with pumitamig (BNT327) plus chemotherapy regimen.
干预措施: Nab-paclitaxel/Paclitaxel (Drug)
Arm 2: Placebo + TPC Chemotherapy
Participants will be administered with matching placebo plus chemotherapy regimen.
干预措施: Matching placebo (Drug)
Arm 1: Pumitamig + Treatment of Physician's Choice (TPC) Chemotherapy
Participants will be administered with pumitamig (BNT327) plus chemotherapy regimen.
干预措施: Eribulin (Drug)
Arm 2: Placebo + TPC Chemotherapy
Participants will be administered with matching placebo plus chemotherapy regimen.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 32 months
PFS is defined as the time from randomization to first documented tumor progression (progressive disease assessed by BICR per response evaluation criteria in solid tumors \[RECIST\] v1.1), or death from any cause, whichever occurs first.
Overall Survival (OS)
时间窗: Up to approximately 49 months
OS is defined as the time from randomization to death from any cause.
次要结局
- PFS Rate as Assessed by Investigator(At 6, 12, 18, and 24 months)
- OS Rate(At 6, 12, 18, and 24 months)
- Objective Response Rate (ORR) as Assessed by BICR(Up to approximately 49 months)
- PFS(Up to approximately 32 months)
- ORR(Up to approximately 49 months)
- Duration of Response (DOR)(Up to approximately 49 months)
- Disease Control Rate (DCR)(Up to approximately 32 months)
- PFS Rate as Assessed by BICR(At 6, 12, 18, and 24 months)
- Occurrence of Treatment-Emergent Adverse Events (TEAEs) Including Grade Greater than or Equal to (>=) 3, Serious, and Fatal TEAEs by Relationship(From the first dose of study treatment to the 90-days after last dose of study treatment (up to approximately 57 months))
- Occurrence of Dose Interruption, Reduction, and Discontinuation of Trial Treatment due to TEAEs (including related TEAEs)(From the first dose of study treatment to the 90-days after last dose of study treatment (up to approximately 57 months))
- Change from Baseline in Breast Symptoms Scale of EORTC QLQ-BR42(Baseline up to approximately 49 months)
- Change from Baseline in Functional Assessment of Cancer Therapy-General Version (FACT-G) Overall Bother Item (FACT-GP5)(Baseline up to approximately 49 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Core 30 Questionnaire (QLQ-C30) Global Health Status/Quality-of-Life score (Items 29 and 30)(Baseline up to approximately 49 months)
- Change from Baseline in EORTC QLQ-C30 Physical Functioning(Baseline up to approximately 49 months)
- Change from Baseline in Arm Symptoms Scale of EORTC QLQ-Breast Cancer (BR)42(Baseline up to approximately 49 months)