NCT06774963招募中1 期
A Phase 1, Open-label, Dose Escalation and Dose Expansion Study for LNCB74, a B7-H4 Targeted Antibody Drug Conjugate, as Monotherapy in Participants With Advanced Solid Tumors
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
- 145
- 试验地点
- 28
- 主要终点
- Evaluate the safety and tolerability of LNCB74
研究概览
简要总结
This is an open-label, phase 1, dose escalation and dose expansion study to determine safety and tolerability, and to determine the maximum tolerated dose and / or recommended phase 2 dose of LNCB74 in participants 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
- •The participant provides written informed consent
- •≥ 18 years of age on day of signing informed consent.
- •Participant with histologically or cytologically confirmed diagnosis of advanced unresectable and/or metastatic solid tumors
- •A male participant must agree to use contraception and refrain from sperm donation or expecting to father a child
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential
- •Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
- •Able to provide tumor tissue sample.
- •Willing to undergo fresh tumor biopsy at Screening and On-treatment if archival tissue not available
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Life expectancy greater than or equal to 12 weeks as judged by the Investigator.
- •Have adequate organ function
排除标准
- •A WOCBP who has a positive serum pregnancy test (within 72 hours) prior to treatment.
- •Has received prior investigational agents within 4 weeks prior to treatment.
- •Has received anti-cancer chemotherapy (Immunotherapy (non-antibody-based therapy), retinoid therapy, hormonal therapy within 2 weeks prior to treatment.
- •Has received antibody-based anti-cancer therapy within 4 weeks prior to treatment.
- •Has received targeted agents and small molecules within 2 weeks or 5 half-lives, whichever is longer.
- •Has received prior platinum-based chemotherapy and progressed within 4 weeks of initiating therapy (platinum-refractory disease)
- •Has received an ADC with MMAE payload.
- •Has received prior radiotherapy within 2 weeks of start of study treatment for focal radiation or within 4 weeks for wide-field radiotherapy
- •Has received G-CSF or GM-CSF within 7 days prior to start of study treatment.
- •Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has known active CNS metastases and/or carcinomatous meningitis
- •Has severe hypersensitivity (≥ Grade 3), known allergy or reaction LNCB74 or any of its excipients.
- •Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
- •Has active ≥Grade 2 sensory or motor neuropathy.
- •Has active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy or any clinically significant corneal disease.
- •Has an active infection requiring systemic therapy.
- •Any major surgery within 4 weeks of study drug administration.
- •Toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless the toxicity is either resolved, returned to baseline or Grade 1, or deemed irreversible.
- •Prior organ or tissue allograft.
- •Uncontrolled or significant cardiovascular disease
- •Participants with serious or uncontrolled medical disorders.
- •Participants who are on total parenteral nutrition (TPN)
- •Participants with history of bowel obstruction within one month of screening
- •Participants with history of significant ascites requiring paracentesis within 2 weeks of screening
- •Has a known history of human immunodeficiency virus (HIV) infection with an acquired immune deficiency syndrome (AIDS)-defining opportunistic infection within the last year, or a current CD4 count <350 cells/µl
- •Has known active Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study
- •Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
研究组 & 干预措施
Part 1 - Dose Escalation and Backfills
Experimental
Aim: Doses of LNCB74 will be escalated to determine the maximum tolerated dose (MTD), maximum administered dose (MAD) and/or recommended Phase 2 dose (RP2D). One or more dose levels will be backfilled for safety and additional biomarker data.
干预措施: LNCB74 (Drug)
Part 2 - Dose Expansion / Optimization
Experimental
Aim: The objectives of the Part 2 Dose Expansion/Optimization are: i) to evaluate safety, tolerability, anti-tumor activity, and pharmacodynamics of LNCB74 in a more homogenous population and ii) characterize the minimally safe and effective dose in a particular tumor type and determine recommended Phase 2 dose(s) (RP2D).
干预措施: LNCB74 (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of LNCB74
时间窗: 24 months
Incidence of AEs, SAEs, AEs meeting protocol defined DLT criteria, AEs leading to discontinuation and death, and laboratory abnormalities per NCI CTCAE v5.0
Define a recommended Phase 2 dose (RP2D) of LNCB74
时间窗: Up to 24 months
Maximum tolerated dose (MTD), maximum administered dose (MAD) and/or recommended Phase 2 dose (RP2D) of LNCB74
次要结局
- Characterize the immunogenicity of LNCB74(24 months)
- Objective Response Rate (ORR)(24 months)
- Duration of Response (DOR)(24 months)
- Disease Control Rate (DCR)(24 months)
- Progression Free Survival Rate (PFSR)(6 months)
- Correlate B7-H4 Expression with Objective Response Rate (ORR)(24 months)
- Correlate B7-H4 Expression with Duration of Response (DOR)(24 months)
- Correlate B7-H4 Expression with Disease Control Rate (DCR)(24 months)
- Correlate B7-H4 Expression with Progression Free Survival (PFS)(24 months)
- Progression Free Survival (PFS)(24 months)
- Time to Peak Drug Concentration (Tmax) of LNCB74(Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9)
- Area Under the Curve (AUC) of LNCB74(Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9)
- Half-life (T1/2) of LNCB74(Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9)
- Maximum Serum Concentration (Cmax) of LNCB74(Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9)
研究者
研究点 (28)
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