NCT06639191招募中早期 1 期
A Phase 1 Prospective, Open-label, First-in-human Study to Evaluate the Safety, Tolerability and Biodistribution of [177Lu]Lu-AKIR001 and Its Anti-tumour Effect in Adult Patients With CD44v6 Expressing Solid Tumours
Karolinska University Hospital1 个研究点 分布在 1 个国家目标入组 15 人开始时间: 2026年1月28日最近更新:
适应症
干预措施
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Primary Endpoint - rate of dose limiting toxicities
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and tolerability of increasing doses of [177Lu]Lu-AKIR001, both in relation to tolerable activity of lutetium-177 and the absorbed protein mass dose of AKIR-001 in patients with irresectable or metastatic CD44v6-expressing solid malignancies for whom no reasonable systemic treatment options are be available. The main question it aims to answer is:
• What is the toxicity profile of the study drug [177Lu]Lu-AKIR001 according to the rate of Dose Limiting Toxicities and (Severe) Adverse Events? Participants will receive one [177Lu]Lu-AKIR001 infusion followed by a 6-week safety follow-up period, which can be extended up to 12 weeks. Possible additional infusions of the trial drug, up to a maximum number of four, can be given when clinical benefit is noted and toxicity is deemed acceptable.
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
- •Participant must be 18 years of age or older
- •Willing and able to provide written informed consent
- •Participant has one of the following histologically confirmed metastatic or locally advanced irresectable CD44v6 expressing (confirmed in pre-screening according to the pathology manual (Appendix III) solid malignancy in one of the following groups, with documented disease progression in the last 8 weeks during/after available standard of care treatment options as mentioned below:
- •For anaplastic, poorly differentiated and radioiodine refractory differentiated thyroid cancer (ATC, PDTC, RAI-R DTC):
- •For BRAFv600E mutated tumours: BRAF/MEK inhibitors.
- •For BRAF-wildtype tumours at least one of the following: anthracycline- or taxane containing chemotherapy/ chemoradiotherapy, or other targeted therapies including vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI), targeted therapies aimed at specific moleculo-pathological features (e.g., targeting NTRK, RET, ALK, PD-L1)
- •For PDTC or RAI-R DTC: Radio-iodine refractory disease as deemed by treating physician and disease progression after at least one line of systemic targeted therapy (including VEGF, TKI, NTRK, RET, BRAF inhibitors)
- •For HNSCC:
- •- At least one prior treatment with combination chemotherapy (either platinum based + 5-Fluorouracil or platinum based + taxane) together with PD1-inhibitor pembrolizumab if combined positive score (CPS) ≥1 or EGFR-inhibitor if CPS <1 (or if immunotherapy is contraindicated)
- •For NSCLC
- •- Treatment with at least two lines of systemic therapy, including checkpoint inhibitor based on PD-L1 status and chemotherapy with a platinum-based regimen.
- •For vulvar SCC:
- •- After treatment with first line platinum/paclitaxel+/-bevacizumab +/- pembrolizumab (the latter in case of PD-L1 positivity), and second line with weekly paclitaxel
- •For cervical SCC:
- •After treatment with first line systemic therapy with platinum/paclitaxel+/-pembrolizumab (the latter in case of PD-L1 positivity)
- •Measurable disease per Response Criteria for Solid Tumours (RECIST) v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Life expectancy of at least three months as estimated by the investigator.
- •Adequate organ and bone marrow function within eight days before the first [177Lu]Lu-AKIR001 infusion:
- •Peripheral white blood cells (WBC) ≥3.0 x 109/L
- •Absolute neutrophil count (ANC) ≥ 2,000/mm3
- •Platelet > 100 x 109/L
- •Hemoglobin > 100 g/L.
- •Serum creatinine of ≤ 1.5x ULN or calculated creatinine clearance of ≥ 60 mL/min/1.73 m2 by Cockcroft- Gault
- •Total serum bilirubin ≤ 1.5x ULN (unless due to Gilbert's syndrome, in which case direct bilirubin must be normal)
- •Serum AST and ALT ≤1.5x ULN (or ≤ 5x ULN if participant has liver metastases)
- •Left Ventricular Ejection Fraction >50% on echocardiography
- •Contraceptives
- •Females of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study treatment Phase and for six months after the last dose of study drug. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone- releasing intrauterine devices (IUDs), and copper IUDs. Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception. Women must refrain from donating eggs during this same period. Should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. If a female participant is of child-bearing potential (females are considered not of childbearing potential if they are at least one year postmenopausal and/or surgically sterile), she must have a documented negative serum pregnancy test before any [177Lu]Lu-AKIR001 infusion.
- •Male participant must agree to practice effective barrier contraception (condom) during the entire study treatment period and through four months after the last dose of study drug or agree to completely abstain from heterosexual intercourse.
排除标准
- •Symptomatic brain metastases that are not previously treated and/or that require ongoing steroid-treatment
- •Other malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- •Chemo-, targeted or radiotherapy within the last 4 weeks before enrolment in the study.
- •Ongoing toxicities graded according to the Common Terminology Criteria for Adverse Events (CTCAE) > 1 from previous anti-cancer treatments.
- •Pregnancy or lactation
- •Uncontrolled hypertension, heart, liver, or kidney disease or other medical/ psychiatric disorders.
- •Severe skin diseases requiring systemic anti-inflammatory treatment, including plaque psoriasis, Stevens Johnsons syndrome or dermatomyositis.
- •A known history of Human Immunodeficiency Virus (HIV) infection, hepatitis B (HBsAg reactive) or hepatitis C (HCV RNA detected) infection or active tuberculosis.
研究组 & 干预措施
This is a single arm trial where patients are included in successive cohorts
Experimental
In the successive cohorts, increasing doses of radioactivity (177-Lu) and CD44v6-targeted antibody (AKIR001) are given. A new dose cohort is opened only when toxicity in the previous dose cohort has deemed acceptable by the trial steering committee and the independent Data Safety Monitoring Board.
干预措施: [177Lu]Lu-AKIR001 (Drug)
结局指标
主要结局
Primary Endpoint - rate of dose limiting toxicities
时间窗: From first dose to a minimum of 6 weeks post-dose.
1. Rate of Dose Limiting Toxicities, according to the definition of (S)AEs according to the CTCAE version 5.0. 2. TEAEs, SAEs, clinically significant laboratory abnormalities and deaths 3. AEs ≥ grade 3 according to the CTCAE version 5.0 grading system (CTCAE v 5.0, 2017) during the treatment period
次要结局
- Biodistribution of 177Lu-AKIR001 in major organs and tissues(8 days)
- Biodistribution of 177Lu-AKIR001 in the whole body(8 days)
- Pharmacokinetics of 177-Lu and AKIR001 in major organs(29 days)
- Recommended Phase 2 Dose(From first dose to a minimum of 6 weeks post-dose.)
- Long-term occurrence of adverse events(5 years)
- Antitumor efficacy: duration of response(12 months)
- Anti-tumor efficacy: radiological response(12 months)
- Dosimetry of 177Lu-AKIR001(8 days)
- Anti-tumor efficacy: overall response rate(12 months)
研究者
Renske Altena
Associate Professor, MD PhD
Karolinska University Hospital
研究点 (1)
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相关资讯
Akiram's Targeted Radiotherapy AKIR001 Advances to Next Phase After Completing First Patient Cohort Without Safety Concerns- Swedish biotech Akiram Therapeutics completed the first patient cohort of its Phase I trial for AKIR001, a targeted radiopharmaceutical combining an anti-CD44v6 antibody with lutetium-177 for aggressive solid tumors.
- No dose-limiting toxicities or safety concerns were observed in the initial cohort, allowing the trial to proceed to the next stage as planned at Karolinska University Hospital.
- The study targets patients with difficult-to-treat cancers including anaplastic thyroid, head and neck, gynecological, and non-small cell lung cancers.
- AKIR001 delivers radiation directly to tumor cells while minimizing damage to surrounding healthy tissue through its selective targeting of the CD44v6 cancer marker.last yearAkiram Therapeutics' AKIR001 Receives Clearance for Phase 1 Trial in Advanced Solid Tumors- Akiram Therapeutics' 177Lu-AKIR001, a novel targeted radioimmunotherapy, has been approved to enter Phase 1 clinical trials.
- The Phase 1 trial will primarily assess the safety and tolerability of 177Lu-AKIR001 in patients with advanced solid tumors expressing CD44v6.
- 177Lu-AKIR001 targets the CD44v6 cancer marker and has shown promise in preclinical studies for treating cancers like thyroid, head and neck, and lung cancer.
- The trial, led by Karolinska University Hospital, is set to begin recruitment in fall 2024 and will be funded by multiple foundations.last year