Phase 1/2 Multi-Center Study to Evaluate the Safety and Efficacy of ONCT-808 in Adult Subjects With Relapsed or Refractory Aggressive B-Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 57
- 试验地点
- 4
- 主要终点
- To Evaluate the Incidence of Dose Limiting Toxicities (DLT)
研究概览
简要总结
This is a Phase 1/2 study to investigate the safety and efficacy of the CAR-T therapy, ONCT-808, in patients with relapsed/refractory (R/R) aggressive B cell malignancies.
详细描述
Study ONCT-808-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and anti-tumor activity of ONCT-808 in subjects with aggressive B cell lymphoma (BCL), including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL). The study will be separated into two distinct phases designated as Phase 1 and Phase 2.
After the safety and tolerability of ONCT-808 have been assessed to select the recommended Phase 2 dose (RP2D) in Phase 1, Phase 2 will commence to further validate the dose and evaluate the safety and efficacy of ONCT-808. In Phase 2, subjects with LBCL or MCL will be enrolled into 2 separate dose expansion cohorts.
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
- •Over 18 years old
- •Histologically confirmed aggressive B-cell NHL, including:
- •MCL, with diagnosis confirmed by cyclin D1 overexpression or evidence of t (11;14) translocation
- •LBCL, including:
- •DLBCL NOS
- •Primary mediastinal LBCL
- •High-grade BCL
- •DLBCL arising from follicular lymphoma
- •Follicular lymphoma grade 3B
- •Richter's syndrome
- •Availability of archival tissue for immunohistology, or willing to undergo baseline biopsy if not available
- •R/R with no available therapy. Subject must have:
- •Received prior systemic therapy that has included an alkylating agent, anthracycline, and an anti-CD20 mAb
- •Received and progressed after autologous hematopoietic stem cell transplant (HSCT) or is ineligible for or has refused to receive HSCT
- •Received prior approved CD19 CAR T-cell therapy or is ineligible for or has refused CD19 CAR-T
- •Minimum washout period between previous systemic therapy and leukapheresis includes:
- •Chemotherapy: at least 14 days or 5 half-lives, whichever is shorter
- •Autologous HSCT: at least 3 months
- •CD19 CAR T-cell therapy: at least 6 months
- •≥1 measurable lesion per Lugano criteria (Cheson, 2014)
- •Subject has Fluorodeoxyglucose (FDG)-avid disease.
- •Subject has an ECOG performance status of 0 or
- •Subject has adequate organ function:
- •ALC ≥100/uL
- •ANC ≥1000/uL (≥500/uL if due to lymphoma; growth factors allowed)
- •Hgb ≥8 g/dL (transfusion allowed)
- •Platelets ≥75,000/uL (≥50,000/uL if due to lymphoma; transfusion allowed)
- •CrCL ≥50 ml/min; AST/ALT ≤2.5x ULN, T. bili ≤1.5 mg/dl (except Gilbert's)
- •EF ≥50% by ECHO/MUGA; NCS ECG, NCS pleural effusion; O2 sat >92%
- •Subject has an estimated life expectancy of >12 weeks
排除标准
- •Prior ROR1-targeted therapy
- •Current or anticipated systemic immunosuppressive therapy (e.g., prednisone >5 mg) from LD chemo until Day 28 post ONCT-808 dosing
- •If receiving anticoagulation therapy, subject is unable to hold therapy for 3 days prior and 28 days following ONCT-808 administration
- •Known CNS involvement by malignancy within 6 months
- •H/o or current CNS disorder (e.g., seizure, CVA, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome or any autoimmune disease with CNS involvement) within 6 months of study entry
- •Clinically significant cardiovascular disease (e.g., MI, UA, CABG, or CHF grade ≥2 NYHA within 12 months of planned ONCT-808 dosing) or serious arrhythmia requiring medication
- •Evidence of HIV infection or active HBV, HCV
- •Systemic fungal infection requiring medication in the last 12 months
- •H/o Covid-19 infection with residual lung infiltrate/fibrosis
- •H/o other malignancy except non-melanoma skin cancer or carcinoma in situ not in remission for ≥2 years
- •H/o autoimmune disease resulting in end organ injury or require systemic immunosuppression within last 2 years
- •H/o allogeneic HSCT or organ transplant
研究组 & 干预措施
Phase 1: Dose Escalation
Patients will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by ONCT-808 IV infusion escalated sequentially with a target dose consistent with the dose required by cohort being enrolled to determine Phase 2 dose (RP2d) regimen(s). Participants may receive bridging therapy that is appropriate to the subject's disease and treatment history if clinically indicated to maintain disease stability.
干预措施: ONCT-808 (Biological)
Phase 1: Dose Escalation
Patients will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by ONCT-808 IV infusion escalated sequentially with a target dose consistent with the dose required by cohort being enrolled to determine Phase 2 dose (RP2d) regimen(s). Participants may receive bridging therapy that is appropriate to the subject's disease and treatment history if clinically indicated to maintain disease stability.
干预措施: Bridging Therapy (Drug)
Phase 2: Dose Expansion
Patients with LBCL or MCL will receive ONCT-808 for each RP2D regimen determined in Phase 1.
干预措施: ONCT-808 (Biological)
Phase 2: Dose Expansion
Patients with LBCL or MCL will receive ONCT-808 for each RP2D regimen determined in Phase 1.
干预措施: Bridging Therapy (Drug)
结局指标
主要结局
To Evaluate the Incidence of Dose Limiting Toxicities (DLT)
时间窗: Up to 28 days after the one-time infusion of ONCT-808
This is based on subject treated with ONCT-808. ONCT-808 1x10\^6 CAR T cells/kg: n=3 ONCT-808 3x10\^6 CAR T cells/kg: n=1 ONCT-808 0.3x10\^6 CAR T cells/kg: n=2
次要结局
- Best Metabolic Response Rate Post-Baseline(up to 1 year after the one-time infusion of ONCT-808)