NCT06303505招募中1 期
A Multicenter, First-in-human Dose Escalation and Optimization Phase I/IIa Study to Investigate Safety, Tolerability, PK, and Efficacy of the NaPi2b ADC TUB-040 in Patients With Platinum-resistant High-grade Ovarian Cancer (PROC) or r/r Adenocarcinoma Non-small Cell Lung Cancer (NSCLC)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Tubulis GmbH
- 入组人数
- 250
- 试验地点
- 39
- 主要终点
- Determination of MTD
研究概览
简要总结
The purpose of this multicenter, open label trial (NAPISTAR 1-01) is to evaluate the safety/tolerability, pharmacokinetics and preliminary efficacy of TUB-040 and to find the best dose of TUB-040 in participants with ovarian cancer and Non Small Cell Lung Cancer. TUB-040 is an antibody-drug-conjugate which delivers a topoisomerase I inhibitor to tumor cells which overexpress the target NaPi2b. The study consists of three parts: In dose escalation, ovarian cancer participants and lung cancer participants receive increasing doses of TUB-040 until the maximal tolerated dose is found. In dose optimization, at least two doses are compared with each other to determine which dose is optimal for participants. In dose expansion, a single dose will be used in a larger number of participants.
TUB-040 is given IV every 3 weeks until the disease progresses or the participants has to stop due to side effects.
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
- •(for all phases)
- •Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of consent.
- •Disease not amenable to curative intent treatment.
- •Participants have exhausted the standard of care treatment (SoC) with expected survival benefit and are not denied SoC with expected survival benefit by participating in the trial.
- •Participants with previous systemic topoisomerase I inhibitor treatment (e.g., Topotecan) are allowed in the study.
- •Radiologically measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the INV.
- •Eastern Cooperative Oncology Group (ECOG) 0-
- •Have a life expectancy of more than 12 weeks for disease-related mortality, as evaluated by the INV.
- •Participants must be willing to sign an archival tissue release form for research purposes and determination of biomarker expression.
- •Participants must be willing to undergo a non-contrast high resolution computed tomography (HRCT) of the thorax scan and pulmonary function testing (PFT) at screening.
- •Adequate organ function
- •Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤grade 1 (except alopecia, hyperpigmentation, or discoloration (incl. vitiligo) of the skin and nails, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic grade 2 peripheral sensory neuropathy after prior taxane therapy or anticancer treatment such as but not limited to IOs).
- •Participants of childbearing potential (FCBP) who are sexually active with a non-sterilized partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions until the end of exposure, plus 5 half-lives and 6 months add-on in the case of participants assigned female at birth.
- •In the opinion of the investigator, the participant must be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations.
- •The participant must not have a history of non-compliance with medical regimens or be considered potentially unreliable and/or uncooperative.
- •The participant must be willing to sign and date the informed consent form (ICF)
排除标准
- •(for all phases)
- •The participant is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.
- •History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.
- •Participants are not allowed to participate in interventional clinical studies either concurrently or within the previous 28 days or within 5 half-lives of any investigational pharmacologic agents or imaging materials, including dyes, investigational surgical techniques, or devices.
- •Participants with spinal cord compression or active central nervous system disease, and/or carcinomatous meningitis.
- •Prior radiotherapy <2 weeks from trial inclusion.
- •Major surgery within 21 days prior to signing the ICF, unless the participant is recovered at that time.
- •Has a history of non-infectious ILD/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.
- •Has an oxygen saturation of <93% on room air at rest.
- •Has a QTcF >470 ms
- •History of nephrotic syndrome
- •Active corneal disease, or history of corneal disease within 12 months prior to enrollment.
- •Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the investigator, would predispose the participant to the development of complications from the administration of protocol therapy.
- •History of another malignancy with ongoing treatment or not yet free from disease for 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
- •Documented other concurrent non-malignant comorbidities such as unstable or uncontrolled pectoral angina, myocardial infarction during the last 6 months, valvular heart disease that requires treatment, acute myocarditis, or congestive heart failure (CHF) (New York Heart Association III or IV).
- •Any anti-tumor chemotherapy, systemic anti-cancer therapy, radiotherapy (except for local radiation therapy of lesions that may cause imminent complications), hormonal therapy, immunotherapy, or corticoid therapy.
- •Concurrent use of strong inhibitors or strong inducers of CYP3A4
- •Live vaccines within 30 days prior to study entry.
- •Participants with acute or chronic infections such as:
- •Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have an undetectable HBV viral load prior to randomization.
- •Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
- •HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease
- •Any other known unresolved and active bacterial, viral, fungal, mycobacterial, or other infection at screening.
- •History of severe and recurrent infections per INV judgment.
- •History of progressive multifocal leukoencephalopathy
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Platinum resistant ovarian cancer
Experimental
干预措施: TUB-040 (Drug)
Platinum resistant ovarian cancer in combination with Bevacizumab
Experimental
干预措施: TUB-040 (Drug)
Non small cell lung cancer-adenocarcinoma
Experimental
干预措施: TUB-040 (Drug)
结局指标
主要结局
Determination of MTD
时间窗: From enrollment until 30 days after last study drug
The highest dose is defined at which no more than 1 of 3 patients have had a Dose Limiting Toxicity (DLT) according to NCI CTCAE V5.0 criteria
Phase 1: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)[
时间窗: First dose up to 21 days
Phase 1 and 2a: Percentage of Participants Experiencing Treatment-Emergent Adverse Event (TEAEs)
时间窗: First dose date up to 30 days post last dose (Up to 3 years)
Phase 2a & 2b: Overall Response Rate (ORR) by Blinded Independent Central Review (BICR)
时间窗: Up to 3 years
ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by BICR.
次要结局
- The time taken to reach the maximum concentration (Tmax)(From enrollment until 30 days after last study drug)
- Determination of immunogenicity(From enrollment until 30 days after last study drug)
- Determination of efficacy(From enrollment until 30 days after last study drug)
- Through plasma/serum concentration (Cmin)(From enrollment until 30 days after last study drug)
- Maximum plasma/serum concentration (Cmax)(From enrollment until 30 days after last study drug)
- Half life (T1/2)(From enrollment until 30 days after last study drug)
- Area Under Curve (AUC)(From enrollment until 30 days after last study drug)
- Phase 2a & 2b: Duration of Response (DOR) by BICR(Up to 3 years)
- Phase 1, 2a & 2b: ORR by INV(Up to 3 years)
- Phase 1, 2a & 2b: DOR by INV(Up to 3 years)
- Phase 1, 2a & 2b: Progression-Free Survival (PFS) by INV(Up to 3 years)
- Phase 1, 2a & 2b: Disease Control Rate (DCR) by INV(Up to 3 years)
- Phase 2a & 2b: Progression-Free Survival (PFS) by BICR(Up to 3 years)
- Phase 2a & 2b: Disease Control Rate (DCR) by BICR(Up to 3 years)
- Phase 1, 2a & 2b: Percentage of Participants Experiencing Grade ≥3 Lab Abnormalities(First dose date up to last dose date plus 30 days)
- Phase 1: Percentage of Participants Experiencing Serious Adverse Events (SAEs)(First dose date up to 30 days post last dose (Up to 3 years))
- Phase 1 & 2a: Pharmacokinetic (PK) Parameter of TUB-040, total mAb, and Free Exatecan: Cmax(Up to 3 years)
- Phase 1 & 2a: PK Parameter of TUB-040, Total mAb, and Free Exatecan: Cmin(Up to 3 years)
- Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Tmax(Up to 3 years)
- Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Area Under Curve (AUC)(Up to 3 years)
- Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Half life (T1/2)(Up to 3 years)
- Phase 1, 2a & 2b: Percentage of Participants Developing anti-TUB-040 antibodies and semiquantitative titer assessments(From enrollment until 30 days after last study drug)
- Phase 2a & 2b: Overall Survival (OS)(Up to 3 years)
- Phase 2a & 2b: CA-125 response according to Gynecological Cancer InterGroup (GCIG)(Up to 3 years)
- Phase 2a & 2b: Percentage of Participants Experiencing TEAEs(First dose date up to 30 days post last dose date (Up to 3 years))
研究者
研究点 (39)
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