NCT05652868终止1 期
A Phase 1 Multicenter Dose Escalation and Dose Expansion Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer - KisMET-01
Mythic Therapeutics55 个研究点 分布在 6 个国家目标入组 227 人开始时间: 2023年3月23日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 227
- 试验地点
- 55
- 主要终点
- Part 1: Number of patients with dose limiting toxicity (DLT)
研究概览
简要总结
This is a Phase I open label multi-center study to evaluate the safety, tolerability, pharmacokinetics and preliminary effectiveness of the investigational drug MYTX-011 in patients with locally advanced, recurrent or metastatic NSCLC. MYTX-011 is in a class of medications called antibody drug conjugates (ADCs). MYTX-011 is composed of a pH-dependent anti-cMET antibody and the potent antimicrotubule drug monomethyl auristatin E (MMAE).
详细描述
The study will be conducted in 2 parts. Part 1 will assess the safety and tolerability of MYTX-011 and identify the dose to be studied in Part 2. Part 2 will include subjects with NSCLC with cMET overexpression or MET amplification/exon 14 skipping mutations, populations with a current unmet medical need.
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
- •Histologically or cytologically confirmed locally advanced, recurrent or metastatic NSCLC and have received available standard of care therapy.
- •There is no limit on the number of prior therapies that can have been received.
- •Part 2 Cohorts A-D and F
- •Known to not have an actionable EGFR mutation. Subjects with or without other driver mutations are permitted to enroll.
- •Must have received (or be ineligible for) available standard of care therapy.
- •Must have progressed on at least 1 line of prior systemic therapy in the locally advanced/metastatic setting. Note: multiple TKIs for the same actionable mutation count as 1 line of therapy. Rechallenge of the same therapy regimen within 6 months of discontinuation date of the therapy is not considered a separate line of therapy. Maintenance therapy is not considered a separate line of therapy. Adjuvant and neoadjuvant therapies count as 1 line of therapy if given within 6 months before study entry. The same rules above apply to all inclusion/exclusion criteria regarding prior lines of therapy.
- •Subjects without any actionable gene alteration: must have progressed on (or be considered ineligible for), or be intolerant to, platinum-based chemotherapy and immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy) and have not received more than 2 lines of prior systemic therapy in the locally advanced/metastatic setting.
- •Subjects with actionable gene alterations (other than EGFR) for which immune checkpoint inhibitor therapy is not standard of care (e.g., anaplastic lymphoma kinase [ALK] translocation): must have progressed on (or be considered ineligible for), or be intolerant to, anticancer therapy targeting driver gene alterations and platinum-based chemotherapy and have not received more than 3 lines of prior systemic therapy in the locally advanced/metastatic setting.
- •Subjects with actionable gene alterations (other than MET exon 14 skipping mutation) for which immune checkpoint inhibitor is standard of care: must have progressed on (or be considered ineligible for), or be intolerant to, anticancer therapy targeting driver gene alteration and platinum-based chemotherapy, and also progressed on (or be considered ineligible for) or be intolerant to immune checkpoint inhibitor(as monotherapy or in combination with platinum-based chemotherapy, and have not received more than 3 lines of prior systemic therapy in the locally advanced/metastatic setting.
- •Subjects with MET exon 14 skipping mutation must have progressed on, or be intolerant to, at least one MET TKI if available, and have not received more than 2 lines of prior systemic therapy in the locally advanced/metastatic setting.
- •Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC without EGFR mutation.
- •Tumor sample with high cMET expression by IHC confirmed by central laboratory testing.
- •Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC without EGFR mutation.
- •Tumor sample with intermediate cMET expression by IHC confirmed by central laboratory testing.
- •Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC without EGFR mutation.
- •Tumor sample with intermediate cMET expression by IHC confirmed by central laboratory testing.
- •Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic squamous NSCLC without EGFR mutation.
- •Tumor sample with cMET expression by IHC confirmed by central laboratory testing.
- •Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous or adenosquamous NSCLC without EGFR mutation.
- •Tumor sample with low cMET expression on tumor biopsy confirmed centrally by IHC that does not meet inclusion criteria for Cohorts A, B, or B
- •Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for a curative therapy), or metastatic NSCLC with actionable EGFR mutations.
- •Tumor sample with high or intermediate cMET expression by IHC confirmed by central laboratory testing.
- •Must have received an available standard of care therapy and have progressed on at least 1 and no more than 3 lines of prior systemic therapy in the locally advanced/metastatic setting.
- •Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic NSCLC with actionable EGFR mutations.
- •Tumor sample with high or intermediate cMET expression by IHC confirmed by central laboratory testing.
- •Must have received an available standard of care therapy and have progressed on at least 1 line and no more than 3 lines of prior systemic therapy in the locally advanced/metastatic setting.
- •Have histologically or cytologically confirmed locally advanced non-squamous or adenosquamous NSCLC without EGFR mutation.
- •Have ultra-low cMET expression on tumor biopsy confirmed centrally by IHC that does not meet inclusion criteria for Cohorts A,B, B2, or D.
- •All patients (Part 1 and Part 2)
- •Inclusion Criteria:
- •Patient has at least one measurable lesion per RECIST 1.1
- •ECOG performance status 0 or 1
- •For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective method of birth control for the duration of the study treatment and for at least 6 months after the last dose of study drug.
- •Able to provide informed consent, and willing and able to comply with study protocol requirements
排除标准
- •Radiation to the lung within 6 weeks prior to screening. For all other sites (except lung), therapeutic or palliative radiation within 2 weeks prior to the first dose of study drug. Must have recovered from all radiation-related toxicity.
- •Major surgery within 28 days of first dose of study drug administration.
- •Untreated, uncontrolled central nervous system (CNS) metastases and/or leptomeningeal disease.
- •History of interstitial lung disease or pneumonitis that required treatment with systemic steroids or evidence of active interstitial lung disease or pneumonitis. A history of prior radiation pneumonitis in the radiation field (fibrosis) is permitted.
- •Clinically significant systemic illness that could pose undue risk to the subject or confound the ability to interpret study results.
- •Active infection requiring IV antibiotics, antivirals, or antifungal medication within 14 Days of Cycle 1 Day 1
- •Neuropathy > Grade 1
- •History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease.
- •Active or chronic corneal disorder
- •Conditions that may interfere with assessment of vision, such as monocular status or severe visual impairment in 1 or both eyes
研究组 & 干预措施
Part 1 Dose Escalation
Experimental
Part 1 patients will receive MYTX-011.
干预措施: MYTX-011 (Drug)
Part 2 Cohort A
Experimental
Part 2 Cohort A patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1.
干预措施: MYTX-011 (Drug)
Part 2 Cohort B
Experimental
Part 2 Cohort B patients will receive MYTX-011 at the recommended phase 2 dose.
干预措施: MYTX-011 (Drug)
Part 2 Cohort C
Experimental
Part 2 Cohort C patients will receive MYTX-011 at the recommended phase 2 dose.
干预措施: MYTX-011 (Drug)
Part 2 Cohort D
Experimental
Part 2 Cohort D patients will receive MYTX-011 at the recommended phase 2 dose.
干预措施: MYTX-011 (Drug)
Part 2 Cohort E
Experimental
Part 2 Cohort E patients will receive MYTX-011 at the recommended phase 2 dose.
干预措施: MYTX-011 (Drug)
Part 2 Cohort B2
Experimental
Part 2 Cohort B2 patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1
干预措施: MYTX-011 (Drug)
Part 2 Cohort E2
Experimental
Part 2 Cohort E2 patients will be randomized to two different dose levels of MYTX-011. Doses to be determined after completion of Part 1
干预措施: MYTX-011 (Drug)
Part 2 Cohort F
Experimental
Part 2 Cohort F patients will receive MYTX-011 at the recommended phase 2 dose.
干预措施: MYTX-011 (Drug)
结局指标
主要结局
Part 1: Number of patients with dose limiting toxicity (DLT)
时间窗: Up to Day 21
The dose limiting toxicities will be based on number and severity of treatment-related adverse events.
Part 2: Number of patients with tumor response
时间窗: 2 years
The overall response rate will be based on number of complete responses and partial responses.
次要结局
- Part 1: OS(for up to 2 years after end of treatment)
- Part 1: Pharmacokinetic (PK) parameter (Total ADC)(24 months)
- Part 1: Pharmacokinetic (PK) parameter (Total antibody)(24 months)
- Part 1: Pharmacokinetic (PK) parameter (Free MMAE)(24 months)
- Part 1: ADA(24 months)
- Part 1: ORR(24 months)
- Part 1: DOR, TTR, DCR(2 years)
- Part 1: PFS(for up to 2 years after end of treatment)
研究者
研究点 (55)
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