A Phase 1 (First-In-Human [FIH]), Multi-Site, Dose Escalation and Expansion Study of WTX-330 in Adult Patients With Advanced or Metastatic Solid Tumors or Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 9
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
A first-in-human, Phase 1, open-label, multicenter study of WTX-330 administered as a monotherapy to patients with advanced or metastatic solid tumors or non-Hodgkin lymphoma.
详细描述
This is a first-in-human, Phase 1, open-label, multicenter study to evaluate the safety, tolerability and preliminary efficacy of WTX-330, a conditionally-activated IL-12 prodrug, when administered as a monotherapy to patients with advanced or metastatic solid tumors or non-Hodgkin lymphoma. Dose escalation will be conducted in patients with advanced and/or metastatic solid tumors who are refractory to all standard of care therapies. Dose expansion will be conducted in two arms: Arm A will enroll patients with indications for which a checkpoint inhibitor (CPI) is indicated/approved who demonstrate primary or secondary resistance to an anti-PD(L)1 treatment regimen, and Arm B will enroll patients with tumor types for which CPI therapy is not indicated/approved.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Age ≥ 18 years.
- •Dose Escalation: A diagnosis of a relapsed/refractory advanced or metastatic solid tumor for which the patient has progressed on or is intolerant of standard therapy, or for whom no standard therapy with proven benefit exists.
- •Dose Expansion: A diagnosis of a relapsed/refractory advanced or metastatic malignancy for which the patient has progressed on or is intolerant of standard therapy, or for whom no standard therapy with proven benefit exists. For Arm A, patients must have a tumor type for which a CPI is indicated/approved and demonstrate primary or secondary resistance to a standard of care anti-PD(L)1-based treatment regimen. For Arm B, patients must have a solid tumor type for which a CPI is not indicated/approved or non-Hodgkin lymphoma.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •At least one measurable lesion per RECIST 1.1 or an evaluable lesion per Lugano classification (for lymphoma).
- •Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor or lymphoma lesion.
- •HIV-infected patients must be on antiretroviral therapy and have well-controlled disease.
- •Adequate organ and bone marrow function.
- •Willingness of men and women of reproductive potential to use highly effective birth control for the duration of treatment and for 4 months following the last dose of study drug.
- •Additional criteria may apply.
排除标准
- •A history of another active malignancy (i.e., a second cancer) within the previous 2 years, except for localized cancers that are not related to the current cancer being treated, are considered cured, and, in the opinion of the Investigator, present a low risk of recurrence. These exceptions include but are not limited to basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
- •Received prior treatment with IL-12, including by intratumoral injection.
- •Patients with primary CNS malignancies.
- •Presence of CNS metastases that are symptomatic and/or require local CNS directed therapy (such as XRT or surgery) or increasing doses of corticosteroids within 2 weeks prior to the first dose of study drug. Patients with treated brain metastases should be neurologically stable and receiving ≤ 10 mg per day of prednisone or equivalent prior to study entry.
- •Significant cardiovascular disease.
- •Significant electrocardiogram (ECG) abnormalities
- •Active autoimmune disease requiring systemic treatment in the past 2 years.
- •Diagnosis of immunodeficiency, on immunosuppressive therapy, or receiving chronic systemic or enteric steroid therapy (dose > 10 mg/day of prednisone or equivalent).
- •Prior receipt of an allogeneic stem cell transplant or allogeneic CAR-T cell therapy.
- •Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose of study drug.
- •Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine, or anticancer herbal remedy) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug.
- •Radiotherapy within 2 weeks of the start of study treatment. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
- •Any unresolved toxicities from prior therapy greater than NCI-CTCAE version 5.0 Grade 1 at the time of starting study drug with the exception of alopecia and Grade 2 platinum therapy-related neuropathy.
- •Use of sensitive substrates of major CYP450 isozymes.
- •Any illness, medical condition, organ system dysfunction, or social situation (including mental illness or substance abuse), that may interfere with a patient's ability to sign the ICF, adversely affect the patient's ability to cooperate and participate in the study, or compromise interpretation of study results.
- •Received a live vaccine within 30 days of the first dose of study drug.
- •Active, uncontrolled systemic bacterial, viral, or fungal infection.
- •HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
- •Active infection with hepatitis B as determined by hepatitis B surface antigen and hepatitis B core antibody, or hepatitis B virus deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction (qPCR) testing.
- •Active infection with hepatitis C as determined by hepatitis C virus (HCV) antibody or HCV RNA by qPCR testing.
- •Pregnant or lactating.
- •History of hypersensitivity to any of the study drug components.
- •Additional criteria may apply
研究组 & 干预措施
WTX-330 dose escalation
Patients with relapsed/refractory advanced or metastatic solid tumors
干预措施: WTX-330 (Drug)
WTX-330 dose expansion in patients for whom CPI therapy is indicated (Arm A)
WTX-330 dose expansion in patients with tumor types for which a CPI is indicated/approved who demonstrate primary or secondary resistance to an anti-PD(L)1-based regimen
干预措施: WTX-330 (Drug)
WTX-330 dose expansion in patients for whom CPI therapy is not indicated (Arm B)
WTX-330 dose expansion in patients with tumor types for which a CPI is not indicated/ approved
干预措施: WTX-330 (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs)
时间窗: 4 weeks
A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle of treatment with WTX-330 and meets any of the criteria included in the protocol
Incidence of Treatment Emergent Adverse Events
时间窗: 24 months
AEs were graded and documented in accordance with NCI-CTCAE version 5.0
Incidence of Changes in Clinical Laboratory Abnormalities
时间窗: 24 months
Change from baseline is provided as baseline grade or "normal/low/high" and worst post-baseline grade.
Investigator-assessed Objective Response Rate (ORR) by RECIST 1.1 and Immune ORR by iRECIST (for Solid Tumors) or Response by Lugano Criteria (for Lymphomas)
时间窗: 24 months
RECIST = Response Evaluation Criteria in Solid Tumors
次要结局
- Plasma Concentrations of WTX-330 Cycle 1 - C Max(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1)
- Plasma Concentrations of WTX-330 Cycle 2 - Time of Maximum Concentration Observation(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 2)
- Plasma Concentrations of WTX-330 Cycle 2 - Half Life(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 2)
- Plasma Concentrations of WTX-330 Cycle 2 - AUC(14 days)
- Plasma Concentrations of WTX-330 Cycle 1 - Time of Maximum Concentration Observation(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1)
- Plasma Concentrations of WTX-330 Cycle 1 - Half Life(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1)
- Plasma Concentrations of WTX-330 Cycle 1 - AUC(14 days)
- Plasma Concentrations of WTX-330 Cycle 2 - C Max(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 2)
- Plasma Concentrations of IL-12 Cycle 1 - C Max(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1)
- Plasma Concentrations of IL-12 Cycle 1 - Time of Maximum Concentration Observation(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1)
- Plasma Concentrations of IL-12 Cycle 1 - Half Life(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1)
- Plasma Concentrations of IL-12 Cycle 1 - AUC(14 days)
- Plasma Concentrations of IL-12 Cycle 2 - Half Life(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 2)
- Plasma Concentrations of IL-12 Cycle 2 - C Max(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 2)
- Plasma Concentrations of IL-12 Cycle 2 - Time of Maximum Concentration Observation(0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 2)
- Antidrug Antibody (ADA) Occurrence(24 months)
- Plasma Concentrations of IL-12 Cycle 2 - AUC(14 days)