NCT06669117招募中1 期
A First-In-Human (FIH) Phase I/II Open-label, Multicentre, Dose Escalation and Expansion Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors Including Non-small Cell Lung Cancer (NSCLC) Harboring Mesenchymal-Epithelial Transition (MET) Alterations
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 19
- 主要终点
- Part2b: Recommended Phase 2 Dose (RP2D): Incidence on overall safety, PK, PDs and cORR
研究概览
简要总结
The goal of this clinical trial is to investigate the safety, the activity of VERT-002 (PFL-002), and the optimal safe dose to be used, in participants with solid tumors including non-small cell lung cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Part 1: histological confirmation of relapsed and/or refractory locally advanced or metastatic solid tumor for which no standard of care treatment is available.
- •Part 2: histological confirmation of locally advanced or metastatic NSCLC Stage IIIB/C or IV (American Joint Commission on Cancer [AJCC] 8th edition) in participants who are not eligible for or should have received available standard of care therapies including curative intent surgery, chemoradiation, radiotherapy or systemic therapy.
- •Part 1: presence of at least one of the following MET alterations based on local documentation of blood or archived tissue results:
- •METex14 mutation
- •MET kinase domain activating gene mutations (e.g. H1094L/R/Y, D1228H/N/V, Y1230A/C/D/H)
- •MET amplification
- •Part 2-a: presence of METex14 mutation (based on local documentation of blood or archived tissue results) and for Part 2-b presence of at least one of the following MET alterations: METex14 mutation (based on local documentation of blood or archived tissue results), de novo MET amplification (based on local documentation of archived tissue results). Confirmation after enrollment in the trial will be performed by central testing from an archival tumor biopsy sample (either tissue block or at least 15 serial cut unstained slides of 5 μm, at least 20% tumor content). In case no archival biopsy is available for central testing, the patient must be willing to have a fresh tumor biopsy sample collected and the tumor biopsy should be deemed safe and feasible by the investigator.
- •Part 2: at least one measurable target lesion according to RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Part 1: participants may have received MET Tyrosine Kinase Inhibitor (TKI) as part of previous treatment, regardless of the line of therapy (first or second line), and regardless of the MET TKI being combined or not. Note: crizotinib will be considered a MET TKI.
- •Part 2: a maximum of 3 prior lines of systemic therapies.
- •Adequate hematologic function.
- •Adequate hepatic function.
- •Adequate renal function.
- •Albumin ≥ 3 g/dL.
- •Adequate coagulation function.
- •Adequate cardiac function.
- •Female participants of childbearing potential must have a negative highly sensitive serum β-HCG test performed within 7 days prior to the first dose of VERT-002 and a negative urine pregnancy test performed at C1D1 prior to the first dose of VERT-
- •Male participants/partners with female spouse/partners of childbearing potential must agree to take appropriate precautions to avoid fathering a child.
- •NOTE: Other protocol defined inclusion criteria may apply.
排除标准
- •Part 2: Documented evidence by local testing of targetable oncogene driver mutations.
- •History of a primary malignancy other than the cancer under trial (as defined for Parts 1 and 2) with the exception of:
- •Participants with a previous malignancy who completed their anticancer treatment at least 2 years before signing informed consent and with no evidence of residual disease from the prior malignancy at screening.
- •Malignancies with a negligible risk of metastasis or death (i.e. 5-year overall survival rate > 90%) that are adequately treated.
- •Uncontrolled Central Nervous System (CNS) metastases or spinal cord compression that are associated with progressive neurological symptoms or require increasing doses of corticosteroids to control the CNS disease.
- •History of hypersensitivity to active or inactive ingredients of VERT-002, or drugs with a similar chemical structure or from a similar class.
- •Active, bacterial, fungal, or viral infection, within 2 weeks prior to the first dose of VERT-002 (C1D1).
- •Positive SARs-CoV-2 or variants of SARs-CoV2 test within 2 weeks prior to first dose administration of VERT-002 (C1D1) or with suspected infection with SARs-CoV-2 or variants of SARs-CoV-2 and confirmation pending.
- •Impaired cardiovascular function or clinically significant cardiovascular disease (either active or within 6 months prior to signing main informed consent).
- •Uncontrolled intercurrent illness including, but not limited to psychiatric illness or social situation that would limit compliance with trial requirements.
- •Past medical history of Interstitial Lung Disease (ILD), drug induced ILD, radiation pneumonitis that requires steroid treatment, or any evidence of clinically active ILD.
- •Women who are pregnant or breastfeeding.
- •Prior anticancer therapy:
- •MET TKI within 7 days prior to the first dose of VERT-002,
- •Any other systemic anticancer therapy within 28 days or 5 half-lives of the anticancer therapy whichever is the shortest, but with a minimum of 14 days interval, prior to the first dose of VERT-002 (C1D1),
- •Radiotherapy to a large field or including a vital organ (including whole brain radiotherapy or stereotactic radiosurgery to brain) within 14 days prior to the first dose of VERT-002 (C1D1).
- •Live attenuated vaccine within 28 days prior to the first dose of VERT-002 (C1D1).
- •Any toxicities from prior therapy with NCI- CTCAE Grade > 1 at the time of the first dose administration of VERT-002 (C1D1). Exceptions include any grade alopecia, fatigue and peripheral neuropathy with a grade ≤
- •Major surgical procedure within 14 days of the first dose of VERT-002 (C1D1).
- •Participation in a clinical trial with administration of an investigational drug within 5 half- lives plus 14 days of the investigational drug, prior to the first dose of VERT-002 (C1D1).
- •NOTE: Other protocol defined exclusion criteria may apply.
研究组 & 干预措施
VERT-002 (PFL-002)
Experimental
Part 1: Dose escalation (Phase Ia): VERT-002 will be administered via intravenous (IV) infusion every 2 weeks. 4 provisional doses are planned. An alternative regimen may be tested informed by the emerging data
Part 2a: Preliminary Activity Assessment (Phase Ib): One dose & schedule selected from Part 1
Part 2b: Dose range optimization (Phase Ib): 2 or 3 doses & schedule selected from Part 1: From the lower limit [Optimal Biologically Active Dose (OBD)] & upper limit [Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) if MTD is not reached]
Part 3: Dose Expansion at RP2D (Phase II): To be defined later on
干预措施: VERT-002 (Drug)
结局指标
主要结局
Part2b: Recommended Phase 2 Dose (RP2D): Incidence on overall safety, PK, PDs and cORR
时间窗: From the start of trial treatment up to 13 months
Safety: All parts: Incidence and severity of treatment emergent adverse events (TEAEs)/serious adverse events (SAEs), according to NCI-CTCAE v5.0 criteria.
时间窗: Screening to Safety Follow-up (30 days post last dose)
Tolerability: All parts: Incidence of TEAEs/SAEs leading to VERT-002 dose reduction, interruption or discontinuation.
时间窗: From screening up to 13 months
Part 1: Maximum Tolerated Dose (MTD): Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: From the start of trial treatment until end of Cycle 1 per dose level
Part 1: Optimal Biologically Active Dose (OBD): Incidence on PK/PD and ORR (Objective Response Rate)
时间窗: From the first VERT-002 intake up to 13 months
Part2a: Preliminary activity assessment: ORR and cORR (Confirmed Objective Response Rate)
时间窗: From the start of trial treatment up to 13 months
次要结局
- All Parts: cORR (Confirmed Objective Response Rate) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 per Investigator's Reviewer (IR)(From the start of the treatment to at least 80% of the participants have been followed up for 24 months)
- Part 2: Progression Free Survival (PFS) according to RECIST v1.1 per IR(From the start of the treatment to at least 80% of the participants have been followed up for 24 months)
- Serum PK Parameter: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Dosing Interval (AUC0-tau)(Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days)
- Serum ADA Parameter: Incidence of VERT-002 anti- drug antibodies (ADA)(Parts 1 and 2: Cycle 1 Days 1,8, and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 8 months). Each cycle is 28 Days)
- All Parts: DCR (Disease Control Rate) based on RECIST version 1.1 per IR(From the start of the treatment to at least 80% of the participants have been followed up for 24 months)
- All Parts: TTR (Time To Response) according to RECIST version 1.1 per IR(From the start of the treatment to at least 80% of the participants have been followed up for 24 months)
- All Parts: Duration Of Response (DOR) according to RECIST v1.1 per IR(From the start of the treatment to at least 80% of the participants have been followed up for 24 months)
- Serum PK Parameter: Maximum Plasma Concentration (Cmax)(Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days)
- Serum PK Parameter: Trough Concentration (Ctrough)(Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days)
- Serum PK Parameter: Accumulation Ratio (Rac) for Maximum Observed Concentration (Cmax) and Area Under The Concentration-Time Curve (AUC)(Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days)
- Part 2: Overall Survival (OS)(From the start of the treatment to at least 80% of the participants have been followed up for 24 months)
研究者
研究点 (19)
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