A Phase 1 Study of IM-1021 in Participants With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 190
- 试验地点
- 31
- 主要终点
- Safety and tolerability of IM-1021 in participants with advanced lymphomas and advanced solid tumors as measured by incidence of treatment emergent adverse events (TEAEs)
研究概览
简要总结
IM-1021-101 is a Phase 1 study to determine the safety and effectiveness of IM-1021 in treating participants with advanced cancer.
详细描述
IM-1021-101 is a 2-part Phase 1 first-in-human, open-label, multicenter dose escalation and expansion study designed to determine the safety, tolerability, pharmacokinetics (PK), and preliminary anti-tumor activity of the ROR1 directed antibody-drug conjugate (ADC) IM-1021. IM-1021 will be administered to participants with advanced B-cell lymphomas and advanced solid tumors. Part A of the study is a dose escalation phase to evaluate safety and tolerability of IM-1021 and to determine recommended doses for further development. IM-1021 will be administered intravenously on an intermittent basis. The safety and tolerability of escalating doses of IM-1021 will be evaluated. Alternative dosing schedules may also be evaluated. Part B of the study is an expansion phase to further evaluate safety and tolerability of IM-1021 at candidate recommended doses in indication specific cohorts of participants. The safety and preliminary efficacy endpoints of this study will inform a preliminary risk-benefit assessment of IM-1021 in this patient population.
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
- •Informed consent signed by the participant prior to conducting study-specific procedures
- •≥18 years of age
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Histological or cytological diagnosis of:
- •Part A: advanced B-cell lymphomas or solid tumors, of the following subtypes:
- •B-cell Lymphomas:
- •Mantle cell lymphoma (MCL)
- •Diffuse large B-cell lymphoma (DLBCL) (including Richter's transformation)
- •Follicular lymphoma
- •Small lymphocytic lymphoma (SLL)
- •Marginal zone lymphoma
- •Solid Tumors:
- •Pancreatic cancer
- •Non-squamous non-small cell lung cancer (NSCLC)
- •Malignant mesothelioma
- •Epithelial ovarian cancer. Participants with fallopian tube and/or peritoneal malignancies are also eligible.
- •Triple-negative breast cancer.
- •Liposarcoma
- •Other, unlisted histologies, if approved by the Sponsor Medical Monitor
- •Part B Cohorts B1, B2, and B3:
- •Histological or cytological diagnosis of the cohort-specific disease indication. Indications may include those listed in Inclusion Criterion 4.a
- •Participants must have adequate organ function.
- •Participants must have a negative pregnancy test, be willing to practice highly effective methods of birth control, use condoms, and refrain from oocyte/sperm donation, as applicable, as detailed in the protocol.
- •Participants must have relapsed or refractory disease and have received all approved and available therapeutic options.
- •Participants must have measurable disease as per the relevant response assessment framework: Lugano Classification for lymphoma (except SLL), per iwCLL criteria for SLL , and per RECIST v.1.1 for solid tumors.
排除标准
- •Previously treated with an ADC with a topoisomerase-1 inhibitor payload, except: Participants with triple negative breast cancer may have received up to one prior ADC with a topoisomerase-1 inhibitor payload.
- •Previously received a ROR1-targeted therapy (eg, ADC, cell therapy, or monoclonal antibody).
- •History of an anaphylactic reaction to irinotecan or ≥ grade 3 GI toxicity to prior irinotecan.
- •Life expectancy < 12 weeks.
- •Prior solid organ transplant.
- •Participants with symptomatic ascites or pleural effusion. Participants who are clinically stable for at least 2 weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis or catheter) are eligible.
- •For participants with known active central nervous system (CNS) disease
- •For participants with solid tumors: Participant has a known active CNS primary tumor or metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no radiological evidence of new or enlarging brain metastases, and are off steroids or on a stable dose up to an equivalent of prednisone 10 mg/day for at least 15 days prior to first dose of study medication. Participants who have symptoms consistent with CNS metastasis must have a negative magnetic resonance imaging (MRI) or other clinically appropriate imaging study if the participant is not able to undergo contrast-enhanced MRI and approved by the Sponsor Medical Monitor during the screening period.
- •For participants with lymphoma: Participant has active cerebral/meningeal disease related to the underlying malignancy. Participants with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior CNS disease has been effectively treated and without progression for at least 3 months.
- •Participant has a known history of malignant primary brain tumor, or another primary solid or hematologic malignancy (other than that under study), unless the participant has undergone potentially curative therapy with no evidence of that disease for at least 2 years. Exception: The time requirement does not apply to participants who underwent successful definitive resection of certain cancers.
- •Participant has certain other significant medical conditions including cardiac, pulmonary, and infectious disease as detailed in the protocol.
- •Participant is pregnant, breastfeeding, or expecting to conceive within the projected duration of the study.
研究组 & 干预措施
Part B: IM-1021 Monotherapy Dose Expansion
IM-1021 given into the vein (IV; intravenously)
干预措施: IM-1021 (Drug)
Part A: IM-1021 Dose Escalation
IM-1021 given into the vein (IV; intravenously)
干预措施: IM-1021 (Drug)
结局指标
主要结局
Safety and tolerability of IM-1021 in participants with advanced lymphomas and advanced solid tumors as measured by incidence of treatment emergent adverse events (TEAEs)
时间窗: From first dose to 37 days following last dose of study treatment
Type, frequency, seriousness, and severity of adverse events (AEs) graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0, including serious adverse events (SAEs), AEs of interest (AEI), AEs leading to discontinuation, and deaths
Determine the recommended dose(s) and schedule(s) of IM-1021 for further development
时间窗: From first dose to 37 days following last dose of study treatment
Type, frequency, seriousness, and severity of AEs graded using the NCI-CTCAE v6.0, including SAEs, AEIs, AEs leading to discontinuation, and deaths
次要结局
- Concentration at end of infusion (Ceoi) of IM-1021 in participants with advanced lymphomas and advanced solid tumors(Through 30-37 days following last dose of IM-1021 up to end of study)
- Maximum observed concentration (Cmax) of IM-1021 in participants with advanced lymphomas and advanced solid tumors(Through 30-37 days following last dose of IM-1021 up to end of study)
- Area under the concentration-time curve (AUC) of IM-1021 in participants with advanced lymphomas and advanced solid tumors(Through 30-37 days following last dose of IM-1021 up to end of study)
- Time to maximum observed concentration (Tmax) of IM-1021 in participants with advanced lymphomas and advanced solid tumors(Through 30-37 days following last dose of IM-1021 up to end of study)
- Apparent Terminal Half-Life (t1/2) of IM-1021 in participants with advanced lymphomas and advanced solid tumors(Through 30-37 days following last dose of IM-1021 up to end of study)
- Characterize the immunogenicity of IM-1021(From first dose to about 30 days following last dose of study treatment)
- Trough Concentration of IM-1021 in participants with advanced lymphomas and advanced solid tumors(Through 30-37 days following last dose of IM-1021 up to end of study)
- To evaluate the preliminary anti-tumor activity of IM-1021 in participants with advanced lymphomas and advanced solid tumors(Week 6 until disease progression or participant discontinuation from study)