An Open-label, Multicenter, Dose Escalation, and Dose Expansion Phase 1/2 Study With Peluntamig (PT217) Followed by a Key ChemotherapY and/or Checkpoint Inhibitor ComBination in Patients With NeuRoendocrIne Carcinomas That Are Known to be DLL3 expressinG CancErs (SKYBRIDGE)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 203
- 试验地点
- 27
- 主要终点
- To determine recommended dose for expansion (RDE) of Peluntamig (PT217).
研究概览
简要总结
This is a first-in-human, Phase 1/2, open-label, dose escalation, dose expansion and combination study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Peluntamig (PT217) as a monotherapy and in combination with chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •18 years or older and able to sign informed consent and comply with the protocol.
- •Measurable disease as defined by RECIST v1.1 criteria for solid tumors.
- •NECs that have transformed from NSCLC are not eligible.
- •Part A: Patients with histologically or cytologically confirmed unresectable advanced or metastatic small cell lung cancer (SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), or extrapulmonary neuroendocrine carcinoma (EP-NEC). Patients with tumors that are of mixed histology are eligible only if neuroendocrine carcinoma/small cell cancer component is predominant and represents at least 50% of the overall tumor tissue. Patients with well differentiated grade 3 neuroendocrine tumors (Ki-67 ≥ 55%) may be considered if their tumors are DLL3 positive.
- •Patients may have progressed after standard of care treatments (at least one line of platinum-based chemotherapy with or without immune checkpoint inhibitor for SCLC patients) or other treatment options, or for whom treatment is not available or not tolerated.
- •Part B: Patients must meet the same eligibility criteria as patients in Part A, C or D.
- •Substudy C1: patients with LCNEC or EP-NEC eligible for first-line (1L) CE treatment. SCLC patients who have relapsed on a 1L treatment (including platinum-based therapy with or without ICI) but remain platinum sensitive (defined as patients who experienced disease progression at least 90 days after their last platinum based chemotherapy) and are eligible for CE treatment rechallenge.
- •Substudy C2: patients with SCLC, LCNEC and EP-NEC eligible for second line (2L) paclitaxel treatment.
- •Substudies C3 and C5: patients with SCLC eligible for 2L or 3L treatment with lurbinectedin (C3) or topotecan (C5) are eligible. Patients with SCLC who progressed on or were intolerant of DLL3-targeting therapies (including but not limited to tarlatamab) can be enrolled into substudies C3 or C5 for 3L treatment.
- •Substudy C4: patients with SCLC, LCNEC or EP-NEC eligible for 2L irinotecan, or patients with SCLC eligible for 3L irinotecan. Patients with SCLC who progressed on or were intolerant of DLL3-targeting therapies (including but not limited to tarlatamab) can be enrolled into substudy C4 for 3L treatment.
- •Substudy D1: will include 2L patients with SCLC, LCNEC, pr EP-NEC (excluding GEP-NEC) that have progressed/relapsed from their first-line treatment that may have included an ICI.
- •Substudy D2: will include 1L ES-SCLC patients that have completed their induction therapy with carboplatin and etoposide plus atezolizumab and are eligible to continue with atezolizumab. These patients must have either stable disease or partial response prior to enrollment.
- •Substudy D3: will include 1L ES-SCLC patients that are treatment naïve or have received C1D1/2/3 and are eligible for treatment with CE plus atezolizumab.
- •Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample (preferably a newly acquired biopsy, or if not possible, archival tissue) to be assessed for DLL3 expression and other biomarkers.
- •ECOG performance status of 0 or
- •Adequate organ function confirmed at screening and within 72 hours of initiating C1D1 of Peluntamig (PT217) treatment.
排除标准
- •Women who are pregnant or lactating.
- •Women of child-bearing potential (WOCBP) who do not use adequate birth control.
- •Autoimmune disease requiring systemic treatment within the past twelve months.
- •Additional inclusion and exclusions criteria will apply.
研究组 & 干预措施
Part A: Dose Escalation
A standard 3+3 dose escalation design will be employed.
干预措施: Peluntamig (PT217) (Drug)
Part B: Dose Expansion
Part B cohorts will open after the dose level considered for RDE has been cleared in Parts A, C and D.
干预措施: Peluntamig (PT217) (Drug)
Part C: Chemotherapy Combination Therapy
Part C of the study will include substudies C1 to C5, combining Peluntamig (PT217) with chemotherapy.
干预措施: Carboplatin + Etoposide (Drug)
Part D: ICI Combination Therapy
In part D, Peluntamig (PT217) will be given in combination with atezolizumab, either alone or in combination with chemotherapy.
干预措施: Peluntamig (PT217) (Drug)
Part D: ICI Combination Therapy
In part D, Peluntamig (PT217) will be given in combination with atezolizumab, either alone or in combination with chemotherapy.
干预措施: Atezolizumab (Drug)
Part C: Chemotherapy Combination Therapy
Part C of the study will include substudies C1 to C5, combining Peluntamig (PT217) with chemotherapy.
干预措施: Lurbinectedin (Drug)
Part C: Chemotherapy Combination Therapy
Part C of the study will include substudies C1 to C5, combining Peluntamig (PT217) with chemotherapy.
干预措施: Peluntamig (PT217) (Drug)
Part C: Chemotherapy Combination Therapy
Part C of the study will include substudies C1 to C5, combining Peluntamig (PT217) with chemotherapy.
干预措施: Paclitaxel. (Drug)
Part D: ICI Combination Therapy
In part D, Peluntamig (PT217) will be given in combination with atezolizumab, either alone or in combination with chemotherapy.
干预措施: Carboplatin + Etoposide (Drug)
Part C: Chemotherapy Combination Therapy
Part C of the study will include substudies C1 to C5, combining Peluntamig (PT217) with chemotherapy.
干预措施: Irinotecan (drug) (Drug)
Part C: Chemotherapy Combination Therapy
Part C of the study will include substudies C1 to C5, combining Peluntamig (PT217) with chemotherapy.
干预措施: Topotecan (Drug)
结局指标
主要结局
To determine recommended dose for expansion (RDE) of Peluntamig (PT217).
时间窗: Through study completion, up to approximately 3 years.
To evaluate the safety and tolerability of Peluntamig (PT217).
时间窗: Through study completion, up to approximately 3 years.
To evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments as assessed by ORR.
时间窗: Through study completion, up to approximately 3 years.
To determine the dose-limiting toxicity (DLT) of Peluntamig (PT217).
时间窗: Through study completion.
To determine the maximum tolerated dose (MTD) of Peluntamig (PT217) if reached.
时间窗: Through study completion.
To determine recommended dose for expansion (RDE) of Peluntamig (PT217).
时间窗: Through study completion.
To evaluate the safety and tolerability of Peluntamig (PT217).
时间窗: Through study completion.
To evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments
时间窗: Through study completion
次要结局
- To evaluate the pharmacokinetics of Peluntamig (PT217).(Through study completion, up to approximately 3 years.)
- To evaluate the immunogenicity (ADA) of Peluntamig (PT217).(Through study completion, up to approximately 3 years.)
- To further evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments(Through study completion, up to approximately 3 years.)
- To further evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments(Through study completion.)
- To evaluate the pharmacokinetics of Peluntamig (PT217).(Through study completion.)
- To evaluate the immunogenicity (ADA) of Peluntamig (PT217).(Through study completion.)