2023-510046-25-00已完成2 期
A first in human Phase 1/2 open-label, multicenter, dose escalation and expansion study of PRS-344/S095012 in patients with solid tumors.
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 16
- 主要终点
- Phase 1: Discontinuation of study treatment due to an AE
研究概览
简要总结
Phase 1:
- To evaluate the safety and tolerability profile of single-agent PRS-344/S095012
- To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended phase 2 dose (RP2D) of PRS-344/S095012
Phase 2: To evaluate the potential anti-tumor activity and efficacy of PRS-344/S095012, as per central assessment according to RECIST v1.1 criteria based on appropriate clinical standards for the specified tumor type
研究设计
- 分配方式
- Na
- 主要目的
- Phase 2- Dose expansion to evaluate the potential efficacy of PRS-344/S095012 in 3 arms
- 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
- 否
入选标准
- •Age ≥18 years on the day the consent is signed.
- •Negative test results for human T-lymphotropic virus 1 (HTLV 1). HTLV testing is only required for participants from countries in which HTLV 1 infection is endemic (Japan, countries in the Caribbean basin,South America, Central America, sub-Saharan Africa, and Melanesia).
- •Dose Escalation: Patients with a histological diagnosis of an unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated.
- •Dose Escalation: Patients must have measurable disease per RECIST 1.1 as assessed by the local site investigator/imaging. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions.
- •Dose Escalation:Patients with no available archived material must have one or more tumor lesions amenable to biopsy
- •Dose Expansion: Patients with histologically diagnosed Arm 1 and 2: recurrent, persistent, and/or metastatic cervical cancer. Acceptable histologies are squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma. Arm 3: locally advanced or metastatic cutaneous squamous cell carcinoma.
- •Dose Expansion: Patients must have received : Arm 1 (cervical , CPI-naïve): at least 1 prior line of platinum-based combination therapy. Patients must not have received any prior treatment with an immune checkpoint inhibitor (anti-PD-1, PD-L1 or anti-CTLA-4 [cytotoxic T lymphocyte-associated protein 4]) and do not have access to an approved immune checkpoint inhibitor. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients. Arm 2 (cervical cancer, CPI-relapsed/refractory): at least 1 prior line of systemic therapy with an immune checkpoint inhibitor as monotherapy or in combination with chemotherapy and/or any other systemic therapies. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate lternative treatment options for these patients. Arm 3 (CSCC, CPI-relapsed/refractory): at least 1 prior line of systemic therapy with an immune checkpoint inhibitor as monotherapy or in combination with chemotherapy and/or any other systemic therapies. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients.
- •Dose Expansion: Biopsy requirements Arms 1 and 2 (cervical cancer): fresh baseline biopsies are mandatory, on-treatment biopsies are optional. Arm 3 (skin cancer): fresh baseline biopsies are mandatory, on-treatment biopsies are mandatory unless medically contra-indicated.
- •Dose Expansion: Patients must have at least one measurable target lesion as per RECIST 1.1 and/or World Health Organization (WHO) criteria for only externally visible skin tumors confirmed by central review. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions
- •Patient must have a life expectancy of at least 3 months.
- •Patient should have a documented disease progression on prior therapy before entry into this study
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Royal Marsden Prognosis score of 0 to 1 (score based on lactate dehydrogenase (LDH) value, albumin value and number of sites of metastasis).
- •Adequate organ function as assessed by laboratory tests within 7 days prior to pretreatment with obinutuzumab: -Lymphocyte count ≥ 800/μ -Gamma-globulin level > 6g/L (by serum protein electrophoresis) or IgG level > 4g/L (by measurement of quantitative immunoglobulins)
- •A female patient must use a highly effective method of birth control during study treatment and until, for 120 days after the last dose of the study treatment. PRS-344/S095012, or 18 months after the last obinutuzumab infusion, whichever comes the latest.
- •A male patient with childbearing potential partners must use a condom during the study and for at least 4 months after the last dose of the study treatment, or 6 months after the last Obinutuzumab infusion, whichever comes the latest. Sperm donation will not be allowed during the study and for 4 months after the last dose of study treatment, or 6 months after the last obinutuzumab infusion, whichever comes the latest.
- •Test should be negative for cytomegalovirus (CMV), Epstein-Barr virus (EBV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infection, according to local standards: - Negative CMV DNA testing in serum or plasma by a sensitive quantitative molecular method. - Absence of immunoglobulin (Ig)M antibodies against EBV-VCA (Viral Capside Antigen) - Negative serologic testing for hepatitis B surface antigen (HbsAg) or a negative result by a sensitive quantitative molecular method for HBVDNA in serum or plasma -Negative HCV RNA testing in serum or plasma by a sensitive quantitative molecular method.
排除标准
- •Patients with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid (≤ 10 mg/day prednisone or equivalent) is allowed
- •Patients who have received prior: a. Chemotherapy, small molecule inhibitors, monoclonal antibodies, antibody-drug conjugates, and/or other similar investigational agent: at least 3 weeks or 5 half-lives prior to first IMP administration, whichever is shorter. b. Radioimmunoconjugates or other similar experimental therapies at least 6 weeks or 5 half-lives prior to first IMP administration, whichever is shorter.
- •Patients who have received a 4-1BB agonist in the past.
- •Patients who had a major surgery within 4 weeks prior to first administration of IMP.
- •Patients who have received either systemic corticosteroids (> 10 mg per day or equivalent) or other immunosuppressive medications during the 2 months prior to the first dose of the study drug. Higher single doses of corticosteroids given as premedication against infusion-related reactions are allowed. Treatment with local steroids (inhaled, intranasal, injected are allowed.
- •Patients with an active infection with a viral, bacterial, or fungal pathogen requiring systemic treatment within seven days before first IMP administration.
- •Patients with a history of an opportunistic infection within a year prior to first IMP administration
- •History of progressive multifocal leukoencephalopathy.
- •Active tuberculosis requiring treatment within 3 years prior to the start of treatment or a suspicion of latent tuberculosis by the investigator.
研究组 & 干预措施
S95012 concentrate solution for infusion 400mg/ 16 ml
Test
干预措施: S95012 concentrate solution for infusion 400mg/ 16 ml (Drug)
Gazyvaro 1,000 mg concentrate for solution for infusion.
Test
干预措施: Gazyvaro 1,000 mg concentrate for solution for infusion. (Drug)
结局指标
主要结局
Phase 1: Discontinuation of study treatment due to an AE
Phase 1: Discontinuation of study treatment due to an AE
Phase 1: Laboratory, electrocardiogram (ECG) and vital sign measurements
Phase 1: Laboratory, electrocardiogram (ECG) and vital sign measurements
Phase 2: Arms 1 and 2: OR as per central assessment according to RECIST v1.1 criteriaper central assessment
Phase 2: Arms 1 and 2: OR as per central assessment according to RECIST v1.1 criteriaper central assessment
Phase 1: Incidence and severity of adverse events (AEs)
Phase 1: Incidence and severity of adverse events (AEs)
Phase 1: Incidence of DLTs
Phase 1: Incidence of DLTs
Phase 2: Arm 3: OR as per central assessment and composite response criteria (digital medical photography and/or imaging as per RECIST v1.1)
Phase 2: Arm 3: OR as per central assessment and composite response criteria (digital medical photography and/or imaging as per RECIST v1.1)
次要结局
- Phase 1: Overall Survival (OS): Defined as the time from first dose of study drug to death due to any cause
- Phase 2: All arms: OR as per investigator assessment, Disease Control (DC), DoR, PFS, OS, Time to Response (TTR)
- Phase 2: AEs, serious adverse events (SAEs), Laboratory, ECG, vital signs
- Phase 2: Serum concentrations of PRS-344/S095012
- Phase 2: Detection of ADA against PRS-344/S095012 and their titration when applicable
- Phase 1: Serum PK parameters of PRS-344/S095012
- Phase 1: Detection of antidrug antibodies (ADA) against PRS-344/S095012 and their titration when applicable
- Phase 1: Objective Response (OR): Defined as Complete Response (CR) plus Partial Response (PR)
- Phase 1: Duration of Response (DoR): defined as the time from first demonstration of response to progression or death, whichever occurs first
- Phase 1: Progression-free Survival (PFS): Defined as the time from the first dose of treatment to first documented disease progression or death due to any cause, whichever occurs first
研究者
Clinical Studies Department
Scientific
Institut De Recherches Internationales Servier IRIS
研究点 (16)
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