A Phase I/IIa, First-in-human, Open-label, Multi-site, Multi-regional, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of BNT3214 in Adults With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- BioNTech SE
- 入组人数
- 533
- 试验地点
- 17
- 主要终点
- All parts - Number and percentage of participants with treatment emergent adverse events (TEAEs)
研究概览
简要总结
This study is the first time the drug BNT3214 (also referred to as PM8102) will be tested in people. It is designed to find out if the drug is safe and how well it works for adults with advanced solid tumors. The study will have three parts. The first two parts (Parts A and B) will focus on testing different amounts of BNT3214 to figure out the best and safest dose. The third part (Part C) will test selected doses of BNT3214 in multiple types of cancer.
详细描述
Parts A and B will investigate the safety and tolerability of BNT3214. Part B is optional and will only be opened if emerging data from Part A indicates that an alternative BNT3214 dosing schedule may have a better benefit-risk profile for further development. Based on the available safety, pharmacokinetics (PK) or preliminary overall response data from Parts A and B, the study may progress to Part C. A study internal review committee will oversee the study to evaluate safety data as the study progresses and/or may recommend the dose levels (DLs) for the dose expansion, possible changes in the schedule of dosing, and expansion indications based on the totality of available data.
There will be no randomization in Parts A and B or the dose expansion cohorts of Part C. In the dose optimization cohorts of Part C, eligible participants will be randomized to one of two DLs selected from Parts A and B. In the dose expansion cohorts, participants will be enrolled into indication-specific cohorts as predefined or may be adjusted per safety, efficacy signals from Parts A and/or B.
Participants will receive BNT3214 for a maximum of 2 years or until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), unacceptable toxicity, withdrawal of consent, loss of clinical benefit as determined by the investigator, lost to follow-up, death, or until the sponsor terminates the study or any other criterion for discontinuation is met, whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Participants aged ≥18 years of age inclusive at the time of giving informed consent.
- •Have at least one measurable tumor lesion based on RECIST v1.
- •One lesion with prior local treatment (i.e., radiotherapy) can be considered measurable only if a disease progression from prior local treatment was demonstrated in the lesion per RECIST v1.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Have a predicted life expectancy ≥3 months.
- •Have histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors that have progressed after at least one available standard therapy; or for whom the standard therapy is considered to be ineffective, inappropriate or intolerable; or for whom a clinical study of an investigational agent is a recognized standard of care.
- •Have adequate liver function as defined in the protocol.
- •Have adequate renal function as defined in the protocol.
- •Have adequate hematologic function as defined in the protocol.
- •Have adequate coagulation as defined in the protocol.
排除标准
- •Untreated or symptomatic central nervous system (CNS) metastases and leptomeningeal disease.
- •Have a primary CNS malignancy.
- •Have active, or a history of, pneumonitis requiring treatment with steroids, or have active, or a history of, interstitial lung disease.
- •Have clinically significant pulmonary complications including, but not limited to, chronic obstructive pulmonary disease, restrictive lung disease, lung injury accompanied with autoimmune disease/connective tissue disorders.
- •Have a history of severe cardiovascular disease.
- •Have a history of significant hematologic toxicity to prior lines of therapy, as assessed by the investigator.
- •Have uncontrolled hypertension or poorly controlled diabetes prior to allocation or randomization.
- •Have concurrent malignancy within 5 years prior to allocation or randomization (protocol defined exceptions apply).
- •Have unstable thrombotic event (e.g., deep vein thrombosis, arterial thrombosis, pulmonary embolism) requiring therapeutic intervention within 3 months prior to allocation or randomization, unless the participant has been fully treated (e.g., inferior vena cava filter placed) and/or adequately anticoagulated on a prophylactic dose.
- •Have known human immunodeficiency virus infection or known acquired immunodeficiency syndrome (protocol defined exceptions apply).
- •Have an active hepatitis B virus infection.
- •Have an active hepatitis C virus (HCV) infection. Participants with a negative HCV antibody test at screening or positive HCV antibody test followed by a negative HCV ribonucleic acid test at screening are eligible. Participants who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.
- •Have adverse reactions from prior anti-tumor therapy that have not returned to Grade ≤1, except for alopecia or toxicities (not specified elsewhere) considered irreversible and posing no safety risk to participants.
- •Have active, or history of, autoimmune disease (e.g., myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, vasculitis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis) (protocol defined exceptions apply).
- •Have serious non-healing wounds, ulcer, or bone fracture.
- •Participants with lung cancer who have major coagulation disorders or an increased risk of hemorrhage (per investigator's clinical judgment)
- •Have a history of serious Grade ≥3 immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy. Participants with a history of Grade ≥3 irAEs that did not lead to treatment discontinuation of a prior immunotherapy should be evaluated and determined by investigators for potential safety risk.
- •Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to allocation or randomization.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment (protocol defined exceptions apply).
- •Have received any of the following therapies or drugs within the noted time intervals prior to allocation or randomization:
- •Systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 10 days prior to the initiation of study treatment.
- •Have been vaccinated with live, attenuated vaccine(s) within 4 weeks prior to initiation of the study treatment.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Part C - Dose expansion of BNT3214
DLs as recommended based on the totality of available data from previous parts.
干预措施: BNT3214 (Drug)
Part A - Escalating DLs of BNT3214
Up to 7 DLs of BNT3214. In Part A, participants will stay on the same DL. In DL1 and DL2, intra-participant dose escalation will be allowed at the discretion of the investigator as specified in the protocol.
干预措施: BNT3214 (Drug)
Part B (optional) - Selected DLs of BNT3214
Up to 4 DLs. The starting dose for Part B will be at least one DL below the DL that has been declared safe for Part A.
干预措施: BNT3214 (Drug)
Part C - Optimized DL of BNT3214
Optimized dose of BNT3214 selected based on totality of data from Parts A and (if conducted) Part B.
干预措施: BNT3214 (Drug)
结局指标
主要结局
All parts - Number and percentage of participants with treatment emergent adverse events (TEAEs)
时间窗: From the time of initiation of the first dose of BNT3214 until 90 days after the last dose of BNT3214
Per DL/cohort. By United States National Cancer Institute Common Terminology Criteria for Adverse Events grading, seriousness, and relatedness.
All parts - Number and percentage of participants with dose interruptions, reductions, and discontinuation of BNT3214 due to TEAEs
时间窗: Up to 24 months
Per DL/cohort.
Parts A and B only - Number and percentage of participants with dose limiting toxicities (DLTs)
时间窗: From first dose up to 28 days
During the DLT evaluation period
Part C only - Objective response rate (ORR)
时间窗: Up to 30 months
Per DL/cohort. Defined as the percentage of participants in whom a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 (based on the investigator's assessment) is observed as best overall response.
次要结局
- All parts - PK assessment: Area under the curve (AUC)(Up to 3 months from first dose of BNT3214)
- All parts - PK assessment: Maximum concentration (Cmax)(Up to 3 months from first dose of BNT3214)
- All parts - PK assessment: Time to maximum observed concentration (Tmax)(Up to 3 months from first dose of BNT3214)
- All parts - PK assessment: Half-life (t1/2)(Up to 3 months from first dose of BNT3214)
- Parts A and B only - ORR(Up to 30 months)
- All parts - Disease control rate(Up to 30 months)
- All parts - Duration of response(Up to 30 months)
- All parts - Anti-drug antibody (ADA) prevalence (percentage of participants who are ADA-positive)(Up to 90 days from the last dose of BNT3214)
- All parts - ADA incidence (percentage of participants having treatment-emergent ADA)(Up to 90 days from the last dose of BNT3214)