2022-503066-74-00
招募中
1/2 期
Phase 1/2a Open-Label, Dose-Escalation, Multicenter, First in-Human, Consecutive-Cohort, Clinical Trial of BI 1910, a Monoclonal Antibody to Tumor Necrosis Factor Receptor 2 (TNFR2), as a Single Agent and in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors
概览
- 阶段
- 1/2 期
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 10
- 主要终点
- Phases 1 and 2a: -Occurrence of adverse events (AEs) or serious adverse events (SAEs). -Changes from baseline in laboratory parameters, vital signs, and physical findings. - Frequency of dose interruptions and dose reductions. -Frequency of AEs leading to discontinuation of study treatment(s).
概览
简要总结
To assess the safety and tolerability profile of BI- 1910 as a single agent and in combination with pembrolizumab in subjects with advanced solid tumors. Phase 1: To determine the maximum tolerated dose (MTD) or maximum administered safe dose (MAD) of BI-1910, as a single agent, and in combination with pembrolizumab. Phase 2a: To determine the recommended Phase 2 dose(s) (RP2D[s]) for further clinical trials.
研究设计
- 分配方式
- Randomized
- 主要目的
- Phase 2 a (Part B)
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Is willing and able to provide signed informed consent for the trial. If the subject does not consent to the genetic testing they may still participate in the trial.
- •11.Subjects who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Note: Subjects should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests are not required unless: • Known history of HBV infection • As mandated by local health authority
- •Subjects with history of HCV infection are eligible if HCV viral load is undetectable at screening. Note: Subjects must have completed curative anti-viral therapy at least 4 weeks prior to randomization. Hepatitis C screening tests are not required unless: • Known history of HCV infection • As mandated by local health authority
- •For subjects who received an anti-PD-1/L1 mAb: a. Has received at least 2 doses of an approved anti-PD-1/L1 mAb. b. Has demonstrated disease progression after anti-PD-1/L1-containing treatment as defined by RECIST v1.
- •c. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
- •Is ≥18 years of age on the day of signing the informed consent form (ICF).
- •Has a histologically confirmed advanced/metastatic solid tumor.
- •Has received standard of care and progressed or is intolerant of, or is not eligible to receive standard of care antineoplastic therapy.
- •Has at least 1 measurable disease lesion as defined by RECIST v1.
- •Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
排除标准
- •Needs doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the trial other than as premedication. During the Screening period, doses of up to 20 mg/day may be given but the dose must be reduced to 10 mg/day within 7 days prior to the first dose of study treatment. Steroids are allowed as premedication in subjects with allergies to contrast scans.
- •Has received a live vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Similarly, COVID-19 vaccines based on viral RNA or protein fragments are allowed. COVID 19 vaccines based on live replicating viral or bacterial vectors (e.g., adenoviruses, adeno-associated viruses, vesicular stomatitis virus, vaccinia viruses, or measles virus) are not allowed.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated CNS metastases may participate provided they are radiologically stable (without evidence of progression for at least 4 weeks by repeat imaging [note that the repeat imaging should be performed during trial Screening]); have no newly onset or worsening symptomatology of brain metastases; and have not required steroids for at least 14 days before study treatment.
- •Has uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: a. Myocardial infarction or stroke/transient ischemic attack within the past 6 months b. Uncontrolled angina within the past 3 months c. Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes). An exception to this criterion is atrial fibrillation with satisfactory cardiac function. d. QT interval prolongation >480 milliseconds (corrected for heart rate using Fridericia’s formula) e. History of other clinically significant heart disease (e.g., cardiomyopathy, congestive heart failure with New York Heart Association functional classification III-IV, pericarditis, significant pericardial effusion, or myocarditis).
- •Has a known psychiatric or substance abuse disorder that would interfere with the subject’s ability to cooperate with the requirements of the trial.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
- •Is participating or planning to participate in another interventional clinical trial or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to first dose of study treatment. Subjects who have entered the follow up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. Participation in an observational trial is acceptable. Subjects who have participated in this clinical trial (22 BI 1910-01) cannot be re-enrolled into another phase of the trial.
- •Has a known additional malignancy of another type, with the exception of adequately treated cone biopsied carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) and basal or squamous cell carcinoma of the skin. Male subjects with asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for >1 year prior to start of study treatment are eligible. Subjects who have undergone potentially curative therapy for a prior malignancy, have no evidence of disease for ≥3 years, and are deemed at negligible risk for recurrence, are also eligible.
- •Has a confirmed diagnosis of primary immunodeficiency or an acquired condition that leads to an immunodeficiency disorder or taking any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
- •Is unable to attend the trial site to receive the study treatment.
结局指标
主要结局
Phases 1 and 2a: -Occurrence of adverse events (AEs) or serious adverse events (SAEs). -Changes from baseline in laboratory parameters, vital signs, and physical findings. - Frequency of dose interruptions and dose reductions. -Frequency of AEs leading to discontinuation of study treatment(s).
Phases 1 and 2a: -Occurrence of adverse events (AEs) or serious adverse events (SAEs). -Changes from baseline in laboratory parameters, vital signs, and physical findings. - Frequency of dose interruptions and dose reductions. -Frequency of AEs leading to discontinuation of study treatment(s).
Phase 1: Occurrence of dose limiting toxicities (DLTs).
Phase 1: Occurrence of dose limiting toxicities (DLTs).
Phase 2a: Identification of dose/dose range fulfilling favorable pharmacokinetic (PK) and pharmacodynamic profile, with acceptable safety (based on the totality of the efficacy, safety, PK, and pharmacodynamic endpoint
Phase 2a: Identification of dose/dose range fulfilling favorable pharmacokinetic (PK) and pharmacodynamic profile, with acceptable safety (based on the totality of the efficacy, safety, PK, and pharmacodynamic endpoint
次要结局
- Phases 1 and 2a: -Calculated standard PK parameters for BI 1910 (including, but not limited to, area under the serum concentration-time curve [AUC], maximum concentration [Cmax], and terminal half-life [t½]). -Incidence and titer of antidrug antibodies (ADAs).
- Phase 1: RDR is defined as the range between MRAD and the MTD/MAD. MRAD is the lowest dose level at which at least 2 subjects experience ≥10% tumor shrinkage and/or relevant PK/PD parameters indicate biological activity: - Response based on RECIST 1:1 and iRECIST. - PK parameters AUC, Cmax, t½. - PD biomarkers such as TNFR2 receptor occupancy immune activation parameters, sTNFR2 and cytokine profiles
- Phase 2a: - Objective response rate (ORR). - Duration of response (DoR).
研究者
Mindaugas Meller
Scientific
Bioinvent International AB
研究点 (10)
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