NCT05320874尚未招募1 期
The Safety, Tolerability, Pharmacokinetic Characteristics and Efficacy of KM257 in Patients With Advanced HER2-positive or Expressing Solid Tumors in a Single-arm, Open-label, Multi-center Phase 1 Clinical Study.
适应症
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 232
- 试验地点
- 1
- 主要终点
- Recommended phase 2 dose (RP2D) (if has) (Part 1a)
研究概览
简要总结
This is a first-in-human, 2-part study to investigate the safety, tolerability, pharmacokinetics and efficacy of KM257 by itself and combined with selected chemotherapy agents in patients with advanced HER2-positive or expressing cancers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand, voluntarily participate and willing to sign the ICF.
- •Male or female subject >= 18 years and =<75 years.
- •Histologically or cytologically confirmed advanced solid tumors.
- •HER2 positive or expressing.
- •ECOG score 0 or
- •According to the definition of RECIST1.1, for Part1a, the patient has evaluable but Non-measurable lesion can be accepted. For Part1b, the patient has at least one measurable lesion.
- •Life expectancy≥12weeks.
- •Adequate organ function.
- •Subjects (women of child-bearing potential and males with fertile female partner) must be willing to use viable contraception method.
排除标准
- •primary CNS tumors (including meningeal tumors), symptomatic or untreated CNS metastases(including meningeal metastases).
- •Subjects who had other malignancies in the 2 years prior to the first administration of the investigational drug were excluded in Phase Ib, except those who had basal cell carcinoma, breast cancer in situ, or cervical cancer in situ and had no recurrence and metastasis after radical therapy.
- •Accepted any other anti-tumor drug therapies within 2 weeks before first dose.
- •Accepted major surgery or radical radiotherapy within 4 weeks before first dose; Accepted palliative radiotherapy within 2 weeks before first dose; Accepted radioactive agents(strontium, samarium, etc.)for therapeutic purposes within 8 weeks before first dose.
- •Participating in other studies involving investigational drug(s) ≤ 4 weeks before the first dose of KM
- •Subjects with interstitial lung disease or non-infectious pneumonia and related history.
- •Infection with HIV disease.
- •Active hepatitis.
- •Had an active infection requiring systemic treatment within 2 weeks prior to initial administration of the investigational drug.
- •Cavity effusion (pleural effusion, ascites, pericardial effusion, etc.) are not well controlled.
- •Subjects are eligible with clinically controlled and stable neurologic function >= 4 weeks, which is no evidence of CNS disease progression; Subjects with
- •Subjects who have received organ transplants.
- •Unresolved toxicities ( Common Terminology Criteria for Adverse Event (CTCAE, version 5), grade greater than or equal to2) from prior anti-cancer therapy. (with the exception of alopecia, the special provisions of inclusion criteria);
- •Subjects who have a history of severe allergic reactions to antibody medications or have a history of severe allergic asthma (CTCAE V5.0 grade ≥3).
- •Subjects with a known history of alcohol or drug abuse.
- •History of myocardial infarction or unstable angina within 6 months prior to enrollment, congestive heart failure (NYHA Class≥2), or clinically significant cardiac disease，LVEF<50%，QTc Fridericia (QTcF) > 470 ms for female, QTc Fridericia (QTcF) > 450 ms for male.
- •History of TIA or stroke within 6 months prior to initial administration of KM
- •Subjects known to have a mental illness that may affect trial compliance.
- •The investigator considers that the subject has any clinical or laboratory abnormalities or other reasons that would disqualify him or her from participating in this clinical study.
- •Part1b cohort 2: subjects with known mutations in exons 2, 3, and 4 of KRAS/NRAS and in V600E of BRAF.
结局指标
主要结局
Recommended phase 2 dose (RP2D) (if has) (Part 1a)
时间窗: Up to 3 weeks
Determine recommended phase 2 dose (RP2D) of KM257.
Objective response rate (ORR) (Part 1b)
时间窗: Up to 2-3 years.
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Maximum tolerated dose (MTD) (Part 1a)
时间窗: Up to 3 weeks
Determine maximum tolerated dose (MTD) of KM257.
Number of patients with adverse events.(Part 1a)
时间窗: Up to 8 months.
Number of patients who experienced an adverse event
次要结局
- Overall survival (OS) (Part1a and Part1b )(up to 2-3 years.)
- Frequency and titer of anti-KM257 antibody. (Part1a and Part1b)(up to 8months for Part1a and up to 2-3 years for Part1b.)
- Number of patients with adverse events (Phase 1b)(up to 2-3 years.)
- Maximum serum concentration (Cmax) of KM257(Part 1a and Part 1b ).(Up to 63days for Part 1a; Up to 63 days for Part1b.)
- Progression free survival (PFS) (Part 1a and Part 1b)(up to 2-3 years.)
- Area under the concentration versus time curve of KM257 in plasma (AUC) (Part 1a and Part1b).(Up to 8 months for Part 1a; Up to 2 to 3 years for Part1b.)
- Time of Maximum observed serum concentration (Tmax) of KM257 (Part1 and Part1b ) .(Up to 63days for Part 1a; Up to 63days for Part1b.)
- Serum Half-life (T-HALF) of KM257. (Part1a and Part1b)(Up to 63days.)
- Objective response rate (ORR) (Part 1a)(Up to 8months.)
- Disease control rate (DCR) (Part 1a and Part 1b)(up to 2-3 years.)
研究者
研究点 (1)
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