A Phase I, First-in-human, Open-label, Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of BNT317 in Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- BNT317 DL1
- 疾病 / 适应症
- Advanced Solid Tumor
- 发起方
- BioNTech SE
- 入组人数
- 39
- 试验地点
- 20
- 主要终点
- Occurrence of DLTs
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
This is a first-in-human (FIH), open-label, multiple-site, dose escalation study which will evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of increasing doses of BNT317 in participants with advanced solid tumors.
详细描述
Participants will be assigned to one of four dose levels of BNT317. One treatment cycle contains one treatment. Participants may receive investigational medicinal product (IMP) for up to 2 years or until they experience disease progression, unacceptable toxicities, withdrawal of consent, study discontinuation or investigator decision. The total duration of the study for a singe participant may be up to 2 years, plus follow-up until the last participant has completed 1 year of survival follow-up (excluding screening). In the dose escalation phase, an accelerated titration design for Dose Level 1 (DL1) and a Bayesian Optimal Interval (BOIN) design for DL2 to DL4 will be used to evaluate dose limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD). Additional dosing schedules and/or intermediate or higher dose levels may be evaluated based on the available safety, antitumor activity, PK, and pharmacodynamic (PD) data.
研究者
入排标准
入选标准
- •Have histologically or cytologically confirmed advanced tumors, who have failed standard therapy, or for whom no standard treatment option is available, or for whom standard therapy is not appropriate.
- •Have at least one measurable lesion based on RECIST 1.
- •Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system \[CNS\] metastasis should not be considered as a measurable lesion).
- •Adequate hematologic and organ function.
排除标准
- •Have received any of the following therapies or drugs within the noted time intervals prior to study treatment:
- •Any prior treatment which inhibits cluster of differentiation 39 (CD39).
- •Vaccination with live attenuated vaccine(s) within 4 weeks prior to the first dose of IMP.
- •Any investigational product within 4 weeks or 5 half lives (if the half life of the other investigational product is known), whichever is longer, before the first dose of IMP in this study or ongoing participation in the active treatment phase of another interventional clinical study.
- •Systemic cytotoxic chemotherapy, immunotherapy within 3 weeks or five half-lives of the chemotherapy (whichever is shorter) prior to the first dose of IMP.
- •Radiation therapy (chest, brain or internal organs) within 4 weeks prior to the first dose of IMP.
- •Palliative radiotherapy to metastasis within 2 weeks prior to the first dose of IMP.
- •Systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 2 weeks prior to the first dose of IMP. Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) is allowed.
- •Have any of the following CNS metastases:
- •Untreated brain metastases that are symptomatic or large (e.g., greater than 2 cm).
研究组 & 干预措施
BNT317 DL1
BNT317 monotherapy
干预措施: BNT317 DL1
BNT317 DL2
BNT317 monotherapy
干预措施: BNT317 DL2
BNT317 DL3
BNT317 monotherapy
干预措施: BNT317 DL3
BNT317 DL4
BNT317 monotherapy
干预措施: BNT317 DL4
BNT317 DL5 (optional, intermediate)
BNT317 monotherapy
干预措施: BNT317 DL5 (intermediate)
BNT317 DL6 (optional, intermediate)
BNT317 monotherapy
干预措施: BNT317 DL6 (intermediate)
BNT317 DL7 (optional, additional)
BNT317 monotherapy
干预措施: BNT317 DL7 (additional)
结局指标
主要结局
Occurrence of DLTs
时间窗: up to 28 days post IMP administration on Day 1 of Cycle 1 or the day before Cycle 3 Day 1, whichever comes earlier (each cycle is 14 days)
Per dose group. During the DLT observation period.
Occurrence of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs)
时间窗: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
Per dose group. Assessed according to (US National Cancer Institute) Common Terminology Criteria for Adverse Events version 5.0, including Grade ≥3, serious, fatal TEAE by relationship.
Occurrence of dose interruption or discontinuation of study treatment due to TEAEs
时间窗: from first IMP administration up to 14 days after the last dose of IMP
Per dose group.
MTD or the recommended phase two dose (RP2D) of BNT317
时间窗: For MTD, up to 28 days post IMP administration on Cycle 1 Day 1 or the day before Cycle 3 Day 1, whichever comes earlier (each cycle is 14 days) or, for RP2D, up to 100 days
次要结局
- Objective Response Rate (ORR)(from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated)
- Duration of Response (DOR)(from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated)
- Disease Control Rate (DCR)(from at least 6 weeks after the first IMP dose up to 100 days after last dose of IMP or until a new anticancer therapy is initiated)
- PK assessment: The maximum (peak) serum concentration (Cmax) of BNT317(from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days))
- PK assessment: Time to reach maximum (peak) serum concentration (Tmax) of BNT317(from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days))
- PK assessment: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time-curve (t1/2) of BNT317(from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days))
- PK assessment: The area under the curve (AUC) from time zero to infinity (mass × time × volume-1) (AUCinf) of BNT317(from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days))
- PK assessment: The AUC from time zero to the end of the dosing period of BNT317(from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days))
- The proportion of participants who are anti-drug antibody (ADA) positive against BNT317(from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated)