NCT04913220终止1 期
A Phase 1/2 Non-randomized, Open-label, Multi-cohort, Multi-center Study Assessing the Clinical Benefit of SAR444245 (THOR- 707) Combined With Cemiplimab for the Treatment of Participants With Advanced Unresectable or Metastatic Skin Cancers
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 46
- 试验地点
- 24
- 主要终点
- All Cohorts: Objective Response Rate (ORR)
研究概览
简要总结
Primary Objective:
-To determine the antitumor activity of SAR444245 in combination with cemiplimab.
Secondary Objectives:
- To determine the recommended phase 2 dose and to assess the safety profile of SAR444245 when combined with cemiplimab
- To assess other indicators of antitumor activity
- To assess the concentrations of SAR444245 when given in combination with cemiplimab
- To assess the immunogenicity of SAR444245
- To assess active concentrations of cemiplimab when given in combination with SAR444245
详细描述
The duration of the study for an individual patient will start from the signature of the main informed consent and include a screening period of up to 28 days, a treatment period [max 35 cycles or until PD], an end-of-treatment visit 30 days + 7 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months after treatment discontinuation and every 3 months following, until disease progression, or initiation of another antitumor treatment, or final cohort cut-off, whichever is earlier
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 country's legal age of majority if >18 years), at the time of signing the informed consent.
- •Participants with:
- •Cohort A: Histologically confirmed unresectable locally advanced or metastatic melanoma that are not amenable to local therapy
- •Cohort B: Histologically confirmed metastatic CSCC or locally advanced
- •CSCC that are not candidates for curative surgery or radiation. Special considerations for the following categories:
- •Participants with tumors arising on the cutaneous hair (non-glabrous) bearing lip with extension onto dry red lip (vermillion) may be eligible after communication with and approval from the Sponsor
- •Participants with the primary site is nose are only eligible if the primary site was skin, not nasal mucosa with outward extension to skin (the Investigator confirmed)
- •Participants with mixed histology in which the predominant histology is invasive CSCC may be eligible after communication with and approval from the Sponsor
- •Participants in both cohorts must have at least one measurable lesion
- •Provision of tumor tissue:
- •For participants in the dose escalation:
- •16 µg/kg: at screening, biopsy is optional but highly recommended; and on-treatment not required
- •24 µg/kg: at screening, biopsy is mandatory and on-treatment, optional but highly recommended
- •For the other participants : Mandatory baseline biopsy for the participants to enroll in cohort A with skin metastasis and in cohort B. Mandatory on-treatment biopsy for participants in Cohort A with skin metastasis and participants in Cohort B.
- •Females are eligible to participate if they are not pregnant or breastfeeding, not a woman of childbearing potential (WOCBP) or are a WOCBP that agrees: to use approved contraception method and submit to regular pregnancy testing prior to treatment and for at least 180 days after discontinuing study treatment and to refrain from donating or cryopreserving eggs for 180 days after discontinuing study treatment.
- •Males are eligible to participate if they agree to refrain from donating or cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved contraception during study treatment and for at least 210 days after discontinuing study treatment.
- •Capable of giving signed informed consent
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≥2
- •Poor organ function
- •Participants with baseline SpO2 ≤92%
- •Active brain metastases or leptomeningeal disease.
- •History of allogenic tissue/solid organ transplant.
- •Last administration of prior antitumor therapy or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter; major surgery or local intervention within 28 days.
- •History of lung disease
- •Comorbidity requiring corticosteroid therapy
- •Antibiotic use (excluding topical antibiotics) ≤14 days prior to first dose of IMP
- •Severe or unstable cardiac condition within 6 months prior to starting study treatment
- •Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years
- •Known second malignancy either progressing or requiring active treatment within the last 3 years
- •For both cohorts:
- •Prior immune checkpoint inhibitors except in the context of adjuvant or neoadjuvant; Participants who were on control arm of a study with an investigational anti-PD-1/PD-L1 are eligible.
- •Received adjuvant or neoadjuvant therapy during the 6 months prior to development of metastatic disease.
- •For Cohort A: any prior systemic treatment for advanced/metastatic disease
- •For Cohort B: >2 prior lines of any systemic treatment for advanced/metastatic disease
- •Inability to undergo any contrast-enhanced radiologic response assessment
- •Receipt of a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Cohort A: Melanoma
Experimental
SAR444245 and cemiplimab administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
干预措施: Cemiplimab (Drug)
Cohort A: Melanoma
Experimental
SAR444245 and cemiplimab administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
干预措施: THOR-707 (Drug)
Cohort B: cutaneous squamous cell carcinoma (CSCC)
Experimental
SAR444245 and cemiplimab administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
干预措施: THOR-707 (Drug)
Cohort B: cutaneous squamous cell carcinoma (CSCC)
Experimental
SAR444245 and cemiplimab administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
干预措施: Cemiplimab (Drug)
结局指标
主要结局
All Cohorts: Objective Response Rate (ORR)
时间窗: From first dose of study treatment administration (Day 1) up to approximately 25 months (Cohorts A and B)
The ORR was defined as the percentage of participants who had best overall response (BOR) as confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or modified world health organization (WHO) response criteria. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 millimeter (mm) (\<1 centimeter \[cm\]). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 27 months (Cohorts A and B))
- All Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs)(From Day 1 to Day 21 of Cycle 1 (each cycle is 21 days: Cohorts A and B))
- All Cohorts: Complete Response (CR) Rate(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B))
- All Cohorts: Time to Complete Response(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B))
- All Cohorts: Time to Response (TTR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B))
- All Cohorts: Duration of Response (DOR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B))
- All Cohorts: Clinical Benefit Rate (CBR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B))
- All Cohorts: Progression Free Survival (PFS)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B))
- All Cohorts: Plasma Concentrations of Pegenzileukin(Cycle 1 Days 2 and 3 (each cycle is 21 days))
- All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin(From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 27 months (Cohorts A and B))
- All Cohorts: Concentration Observed Just Before Study Treatment Administration During Repeated Dosing (Ctrough) of Cemiplimab(Cycles 1, 2, 4, 7, 10, and 15 (each cycle is 21 days))
- All Cohorts: Concentration at End of Infusion (Ceoi) of Cemiplimab(Cycles 1, 2, 4, 7, 10, and 15 (each cycle is 21 days))
研究者
研究点 (24)
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