A Phase 1b/2, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients With Solid Tumors Likely to Express NaPi2b
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 523
- 试验地点
- 1
- 主要终点
- DES and EXP: Safety and Tolerability
研究概览
简要总结
First-in-human, Phase 1b/2 safety study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks. Patients with tumor types likely to express NaPi2b were enrolled in dose escalation. Patients with platinum-resistant ovarian cancer and non-small cell lung cancer (adenocarcinoma subtype) were enrolled in the expansion segment of this study. Patients with platinum-resistant, high-grade serous ovarian cancer were enrolled in the UPLIFT segment of this study. In addition to safety assessments, the pharmacokinetics of the drug were assessed along with ADC activity. A QTc sub-study was added for the UPLIFT cohort for a sub-set of sites.
详细描述
This is a multi-center study of XMT-1536 (upifitamab rilsodotin) in patients with tumors likely to express NaPi2b, focusing on patients with platinum-resistant ovarian cancer and non-small cell lung cancer, adenocarcinoma subtype. XMT-1536 (upifitamab rilsodotin) was administered as an intravenous infusion once every four weeks. The study consisted of three segments: dose escalation (DES), dose expansion (EXP), and the pivotal cohort (UPLIFT). The DES segment studied small groups of patients who received increased doses. A Safety Review Committee was established to review the data from each dose level before moving to the next higher dose. The dose escalation cohort has ended and is no longer enrolling patients. Enrollment into the EXP segment consisted of 2 parallel cohorts of patients to confirm the dose that has been identified in DES and estimate the objective response rate in each patient population. The EXP and UPLIFT cohorts are no longer enrolling patients. All adverse events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria version (CTCAE v5.0). Throughout the study, pharmacokinetics were measured using proprietary assays developed by Mersana. Anti-cancer activity were measured via RECIST.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose Escalation
XMT-1536 (upifitamab rilsodotin) treatment is administered in groups of patients who will receive doses that increase over time.
This cohort is closed to enrollment.
干预措施: upifitamab rilsodotin (Drug)
Dose Expansion - Ovarian Cancer
Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose.
This cohort is closed to enrollment.
干预措施: upifitamab rilsodotin (Drug)
Dose Expansion - NSCLC adenocarcinoma
Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose.
This cohort is closed to enrollment.
干预措施: upifitamab rilsodotin (Drug)
Pivotal Cohort (UPLIFT)
Patients with platinum-resistant ovarian cancer will receive XMT-1536 (upifitamab rilsodotin) to further confirm the efficacy.
This cohort is closed to enrollment.
干预措施: upifitamab rilsodotin (Drug)
QTc Sub-Study
For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536.
This cohort is closed to enrollment.
干预措施: upifitamab rilsodotin (Drug)
结局指标
主要结局
DES and EXP: Safety and Tolerability
时间窗: First dose up until 30 days after study termination
Evaluate incidence and severity of adverse events
DES: Maximum tolerated dose or recommended Phase 2 dose
时间窗: Up to 36 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met
Evaluate adverse events and concomitant medication use after XMT-1536 (upifitamab rilsodotin) doses
EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin)
时间窗: Every 6 weeks for up to 36 weeks
Monitor tumor size
UPLIFT: Investigator-assessed objective response rate (ORR) of XMT-1536 (upifitamab rilsodotin) in the ITT-Higher NaPi2b population
时间窗: Every 8 weeks until disease progression or up to 24 months
Confirmed ORR is defined as the proportion of patients who have achieved a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 after the initiation of study treatment.
QTc Sub-study: Evaluation of the concentration response analysis of XMT-1536 versus the change in QTcF values
时间窗: 60 minutes prior to first dose, up to 26 hours after Cycle 3 dose
"The concentration-QTcf change from baseline deltaQTcF analysis and analysis of central tendency for deltaQTcF
次要结局
- DES: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin)(Every 6 weeks for up to 36 weeks)
- UPLIFT: Confirmed Investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) regardless of NaPi2b expression(Every 8 weeks until disease progression or up to 24 months)
- UPLIFT: Confirmed objective response rate by independent radiology review (IRR) for patients with high NaPi2b and overall(Every 8 weeks until disease progression or up to 24 months)
- DES and EXP: Time of maximum observed concentration of XMT-1536 (upifitamab rilsodotin)(Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses)
- DES and EXP: Maximum concentration of XMT-1536 (upifitamab rilsodotin)(Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses)
- DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin)(Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses)
- DES and EXP: Anti-drug antibody and neutralizing antibody(Every 6 weeks for up to 36 weeks)
- UPLIFT: Duration of objective response (DOR)(4 weeks after first response and every 8 weeks until disease progression or up to 24 months)
- UPLIFT: Incidence and severity of adverse events(First dose up until 60 days after study termination)
- QTc Sub-Study: Evaluation of the effect of XMT-1536 on QTcF in patients with platinum-resistant HGSOC by timepoint analysis(60 minutes prior to first dose, up to 26 hours after Cycle 3 dose)
- QTc Sub-Study: Evaluation of the effect of XMT-1536 on the PR-interval (PR), QRS duration (QRS), Heart Rate (HR), and ECG morphology(60 minutes prior to first dose, up to 26 hours after Cycle 3 dose)