A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XB002 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Exelixis
- 入组人数
- 269
- 试验地点
- 95
- 主要终点
- Dose-Escalation Stage: MTD/recommended dose for XB002
研究概览
简要总结
This is a Phase 1, open-label, multicenter, dose-escalation and expansion study evaluating the safety, tolerability, PK, pharmacodynamics, and clinical antitumor activity of XB002 administered IV q3w alone and in combination with nivolumab or bevacizumab to subjects with advanced solid tumors.
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
- •Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent.
- •Dose-Escalation Stage Cohorts A, AB, and AN: The subject has received at least one systemic standard life-prolonging therapy unless it does not exist, or available therapies are intolerable or no longer effective.
- •Cohort-Expansion Stage (Cohorts B - M, BN, FN and HN): The subject has received standard life-prolonging therapies unless they do not exist, or available therapies are intolerable or no longer effective.
- •Cohort-Expansion Stage Cohort B and BN (Non-small Cell Lung Cancer): Subjects with Stage IV NSCLC who have documented radiographic disease progression during or following their last systemic anticancer therapy.
- •Cohort-Expansion Stage Cohort D (Epithelial Ovarian Cancer): Subjects with high-grade serous ovarian cancer, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC) who have platinum-resistant disease following treatment with platinum-containing chemotherapy.
- •Cohort-Expansion Stage Cohort E (Cervical Cancer): Subjects with persistent, recurrent, or metastatic carcinoma of the uterine cervix who have documented radiographic disease progression during or following their last systemic anticancer therapy.
- •Cohorts F and FN (SCCHN): Subjects with head and neck cancer (squamous cell histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy. Allowed primary tumor locations are oral cavity, oropharynx, hypopharynx, glottic larynx. Note: Excluded are subjects with primary tumor site of the nasopharynx.
- •Cohort G (Pancreatic Cancer): Subjects with pancreatic cancer (adenocarcinoma histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy.
- •Cohort H (Esophageal SCC): Subjects with esophageal cancer (squamous cell histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy. Note: subjects with esophageal adenocarcinoma and adenocarcinoma of gastroesophageal junction (GEJ) are excluded.
- •Cohort I (mCRPC): Subjects with metastatic, castration resistant adenocarcinoma of the prostate. Note: Neuroendocrine differentiation and other histological features are permitted if adenocarcinoma is the primary histology.
- •Cohort J (TNBC): Subjects with triple-negative (estrogen receptor negative [ER-]/progesterone receptor negative [PR-]/ human epidermal growth factor receptor 2 negative [HER-2-]) breast cancer who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
- •Cohort K (HR + BC): Subjects with breast cancer that is hormone receptor-positive (ER+ and/or PR+) and HER-2-) and who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
- •Cohort L (Endometrial Cancer): Subjects with locally advanced, recurrent or metastatic endometrial cancer who have documented radiographic disease progression during or following their last systemic anticancer therapy.
- •Cohort M (Tumor-Agnostic Tissue Factor-Expressing Solid Tumors): Subjects with solid tumors other than those designated in Cohorts B-L and those which express tissue factor. Participation in this cohort will be at selected sites and countries based on site feasibility assessment.
- •Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1 as determined by the Investigator, except for subjects with prostate cancer without soft tissue disease and subjects with primary brain tumors.
- •Tumor tissue material collected no more than 3 years prior to consent, if possible. If archival tumor tissue is not available, a fresh tumor biopsy may be collected from subjects enrolled in the Dose-Escalation Stage and should be collected from subjects in the Cohort-Expansion Stage.
- •Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 [CTCAE v5]) from AEs.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-
- •Adequate organ and marrow function.
- •Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
- •Female subjects of childbearing potential must not be pregnant at screening.
排除标准
- •Receipt of prior therapies as defined in study protocol
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
- •Uncontrolled, significant intercurrent or recent illness.
- •Major surgery within 4 weeks before first dose of study treatment
- •Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG).
- •Pregnant or lactating females
- •Previously identified allergy or hypersensitivity to components of study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies.
- •Another unresolved malignancy or a malignancy that is considered to be cured within 2 years before first dose of study treatment. Note: Subjects with superficial non-melanoma skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy within 2 years before first dose of study treatment are eligible.
研究组 & 干预措施
XB002 Single-Agent Dose-Escalation Cohorts
Subjects (Cohort A) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
干预措施: XB002 (Drug)
XB002 Single-Agent Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with non-small cell lung cancer [NSCLC] (Cohort B), epithelial ovarian cancer (Cohort D), cervical cancer (Cohort E), SCCHN (Cohort F), pancreatic cancer (Cohort G), Esophageal SCC (Cohort H), metastatic castration-resistant prostate cancer (Cohort I), triple-negative breast cancer (Cohort J), hormone-receptor positive breast cancer (Cohort K), endometrial cancer (Cohort L) and tumor agnostic tissue factor-expressing solid tumors (Cohort M).
干预措施: XB002 (Drug)
XB002 + Nivolumab Dose Escalation Cohorts
Subjects (Cohort AN) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
干预措施: XB002 (Drug)
XB002 + Nivolumab Dose Escalation Cohorts
Subjects (Cohort AN) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
干预措施: Nivolumab (Drug)
XB002 + Nivolumab Dose Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with non-small cell lung cancer [NSCLC] (Cohort BN), SCCHN (Cohort FN).
干预措施: XB002 (Drug)
XB002 + Nivolumab Dose Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with non-small cell lung cancer [NSCLC] (Cohort BN), SCCHN (Cohort FN).
干预措施: Nivolumab (Drug)
Experimental: XB002 + Bevacizumab Dose Escalation Cohorts
Subjects (Cohort AB) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
干预措施: XB002 (Drug)
Experimental: XB002 + Bevacizumab Dose Escalation Cohorts
Subjects (Cohort AB) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Dose-Escalation Stage: MTD/recommended dose for XB002
时间窗: 18 months
To determine the MTD and/or RD for further evaluation of IV administration of XB002 alone and in combination therapy in subjects with advanced malignancies
Cohort-Expansion Stage: Objective Response Rate (ORR)
时间窗: 12 months
To evaluate preliminary efficacy of XB002 when administered alone and in combination therapy by determining the ORR per RECIST 1.1 (or other applicable response criteria eg. RANO or PCWG3 criteria) as assessed by the Investigator
次要结局
- Tolerability of XB002 as evaluated by the duration of exposure for the study(30 months)
- Tolerability of XB002 as evaluated dose intensity of the study treatment(30 months)
- Safety of XB002: Adverse Events(30 months)
- Immunogenicity of XB002(30 months)
- Anti-tumor activity of XB002: Objective Response Rate (ORR)(30 months)
- Trough Concentration (Ctrough)(30 months)
- Anti-tumor activity of XB002: Duration of Response (DOR)(30 months)
- Anti-tumor activity of XB002: Progression Free Survival (PFS)(30 months)
- Cohort-Expansion Stage: overall survival(12 months)
- Maximum Plasma Concentration (Cmax)(30 months)