Phase 1 Dose Escalation Study of the Agonist Redirected Checkpoint, SL-172154 (SIRPα-Fc-CD40L) Administered Intravenously in Subjects With Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 6
- 主要终点
- Safety Profile of SL-172154
研究概览
简要总结
This is a Phase 1 first in human, open label, multi-center, dose escalation study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in subjects with ovarian cancer.
详细描述
This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and pharmacodynamic effects of SL-172154 and identify the dose and schedule i.e., recommended Phase 2 dose for future development (RP2D). Subjects eligible for enrollment are required to have platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers. The study design consists of dose escalation cohorts, an optional pharmacodynamic cohort, and an optional dose expansion cohort. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. The study may also enroll a pharmacodynamic cohort to obtain additional pharmacodynamic data at one or more dose levels that have completed evaluation for safety without exceeding the maximum tolerated dose (MTD). Subjects enrolled in the pharmacodynamic cohort will not inform dose escalation decisions. A dose expansion cohort may be opened to further characterize safety, tolerability, PK, anti-tumor activity, and pharmacodynamic data to inform the selection of a RP2D.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants are eligible to be included in the study only if all the following criteria apply:
- •Subject has voluntarily agreed to participate by giving written informed consent in accordance with ICH/GCP guidelines and applicable local regulations.
- •Subject must have a histologically confirmed diagnosis of an unresectable, locally advanced or metastatic ovarian cancer, or primary peritoneal cancer or fallopian tube cancer.
- •Subjects must be refractory or intolerant to existing therapy(ies) known to provide clinical benefit for their condition. Subject must have received platinum-based therapies, and should not be eligible for further platinum therapy, or should be intolerant to such therapy. Subjects with HRD positive disease may participate if they have received prior polyadenosine diphosphate ribose polymerase (PARP) inhibitor therapy given alone or with bevacizumab.
- •Subjects should not be primary platinum refractory as defined by progressing during or within 1 month of upfront platinum therapy.
- •Has measurable disease by RECIST v1.1 using radiologic assessment.
- •Subject age is 18 years and older.
- •Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Has life expectancy of greater than 12 weeks.
- •Has adequate organ function.
- •Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of D1 of IP.
- •Recovery from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade
- •Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies), unless there is excessive risk as determined by the investigator.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Prior treatment with an anti-CD47 or anti-SIRPα targeting agent or a CD40 agonist.
- •Any anti-cancer therapy within the washout period prior to first dose (D1) of SL-
- •Concurrent chemotherapy, immunotherapy, biologic or hormonal/hormonal suppression therapy for cancer treatment is prohibited. Concurrent use of hormones for non-cancer related conditions is acceptable.
- •Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of SL-172154 treatment.
- •Receipt of live attenuated vaccine within 28 days of D1 of IP.
- •Active or documented history of autoimmune disease. Exceptions include controlled Type I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.
- •Hypersensitivity to the active drug substance or to any of the excipients for the agent to be administered or subjects with known hypersensitivity to Chinese hamster ovary cell products.
- •Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.).
- •Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 5 days of D1 of IP).
- •Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal disease associated with diarrhea within 6 months of D1 of IP.
- •Clinically significant or uncontrolled cardiac/thromboembolic disease.
- •Untreated central nervous system or leptomeningeal metastases.
- •Women who are breast feeding.
- •Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or compromised ability to provide written informed consent.
- •Another malignancy that requires active therapy and that in the opinion of the investigator and Sponsor would interfere with monitoring of radiologic assessments of response to IP.
- •Has undergone allogeneic stem cell transplantation or organ transplantation.
- •Known history or positive test for human immunodeficiency virus, or positive test for hepatitis B.
研究组 & 干预措施
SL-172154
Intravenous administration
干预措施: SL-172154 (Drug)
结局指标
主要结局
Safety Profile of SL-172154
时间窗: From Day 1 to 90 days after Last Dose of SL-172154
Number of participants with treatment emergent adverse events
Maximum Tolerated Dose (MTD) of SL-172154
时间窗: From Day 1 to 90 days after Last Dose of SL-172154
Number of participants with dose limiting toxicities (DLTs)
次要结局
- Recommended Phase 2 Dose (RP2D) for SL-172154(Approximately 24 months)
- Assess Preliminary Evidence of Anti-tumor Activity of SL-172154(Approximately 24 months)
- Immunogenicity to SL-172154(Approximately 24 months)
- Maximum Serum Concentration (Cmax) of SL-172154(Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days))
- Minimum Serum Concentration (Cmin) of SL-172154(Cycle 1 Day 15 and Cycle 2 Day 1 (each cycle = 28 days))
- Time at Which Maximum Concentration of SL-172154 is Observed (Tmax)(Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days))
- Area Under the Serum Concentration-time Curve (AUC)(Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days))
- Terminal Elimination Half-life (t1/2)(Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days))
- Clearance (CL)(Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days))
- Volume of Distribution(Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days))