Open-label, Multi-cohort, Phase 2 Trial, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine (SAR408701) Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 50
- 试验地点
- 29
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Primary Objective:
- For Cohort A, Cohort B, and Cohort C Part 2: To assess the antitumor activity of tusamitamab ravtansine in metastatic breast cancer (mBC) and tusamitamab ravtansine monotherapy and in combination with gemcitabine in metastatic pancreatic adenocarcinoma (mPAC)
- For Cohort C Part 1: Confirmation of the recommended tusamitamab ravtansine dose when administered in combination with gemcitabine
Secondary Objectives:
- To assess the safety and tolerability of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine
- To assess other efficacy parameters of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine
- To assess the immunogenicity of tusamitamab ravtansine
- To assess the pharmacokinetics (PK) of tusamitamab ravtansine and gemcitabine when given in combination
详细描述
The expected duration of study intervention for participants may vary, based on progression date and the cohort; median expected duration of study per participant is estimated at 8 months for Cohort A/C and 6 months for Cohort B (up to 1 month for screening, a median of 4 or 2 months for treatment in Cohort A/C and Cohort B respectively, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).
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 at least 18 years of age
- •Participants with at least one measurable lesion according to the RECIST v1.1 criteria that has not been irradiated (ie, newly arising lesions in previously irradiated areas are accepted).
- •Participants with ECOG performance status 0 to
- •Evidence of metastatic disease.
- •Expression of CEACAM 5 by centrally assessed IHC assay.
- •Male and female participants willing to comply with contraceptive use consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Cohort A: mBC
- •Histological or cytologic diagnosis of breast cancer.
- •Have received at least 2 prior cytotoxic chemotherapy regimens for non-TNBC tumor type or at least 1 for TNBC tumor type but not more than 4 in the locally recurrent or metastatic setting.
- •Cohorts B and C: mPAC
- •- Have confirmed diagnosis of pancreatic ductal adenocarcinoma.
- •Cohort B: mPAC:
- •- Have documented radiographic progression or documented intolerance after at least 1 prior systemic chemotherapy line which included either gemcitabine (or relapsed within 6 months of completion of gemcitabine adjuvant therapy) or a 5-fluorouracil based regimen (including capecitabine) but no more than 2 prior chemotherapy lines for locally advanced/metastatic disease.
- •Cohort C: mPAC
- •- Have documented radiographic progression or documented intolerance after 1st line fluoropyrimidine-containing chemotherapy (or relapsed within 6 months of completion of chemotherapy as adjuvant therapy) for locally advanced/metastatic disease.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Medical condition requiring concomitant administration of a medication with a narrow therapeutic window, that is metabolized by cytochrome P450 (CYP450), and for which a dose reduction cannot be considered.
- •Medical conditions requiring concomitant administration of strong CYP3A inhibitor, unless it can be discontinued at least 2 weeks before the first administration of study intervention.
- •Life expectancy less than 3 months.
- •Untreated brain metastases or history of leptomeningeal disease.
- •Significant concomitant illness
- •History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
- •History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or active hepatitis A, B or C infection.
- •Non-resolution of any prior treatment-related toxicity to <Grade 2 according to NCI CTCAE v5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy (HRT).
- •Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy.
- •Use of contact lenses. Participants using contact lenses who are not willing to stop wearing them for the duration of the study intervention are excluded.
- •Concurrent treatment with any other anti cancer therapy.
- •Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is shorter, for prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy, or any investigational treatment).
- •Any prior therapy targeting CEACAM
- •Prior maytansinoid DM4 treatment (ADC).
- •Any major surgery within the preceding 2 weeks of the first study intervention administration.
- •Previous enrollment in this study or current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
- •Poor renal function
- •Poor hepatic function
- •Poor bone marrow function
- •Cohort C: mPAC
- •- Any previous systemic therapy with taxane or gemcitabine (for Cohort C only).
- •The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
研究组 & 干预措施
Cohort A metastatic breast cancer (mBC)
tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)
干预措施: tusamitamab ravtansine (Drug)
Cohort B metastatic pancreatic adenocarcinoma (mPAC)
tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)
干预措施: tusamitamab ravtansine (Drug)
Cohort C Metastatic pancreatic adenocarcinoma (mPAC)
tusamitamab ravtansine every 2 weeks combined with gemcitabine on Day 1, Day 8 and Day 15 every 4 weeks administered via intravenous infusion (IV)
干预措施: tusamitamab ravtansine (Drug)
Cohort C Metastatic pancreatic adenocarcinoma (mPAC)
tusamitamab ravtansine every 2 weeks combined with gemcitabine on Day 1, Day 8 and Day 15 every 4 weeks administered via intravenous infusion (IV)
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)
ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Cohort C (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (28 days)
The following adverse events (AEs) that occurred during the first cycle of treatment, unless due to disease progression or to a cause obviously unrelated to study treatment, were considered DLTs: 1. Hematological abnormalities: grade 4 neutropenia for 7 or more consecutive days, grade 3 to 4 neutropenia complicated by fever or microbiologically or radiographically documented infection, grade greater than or equal to (≥) 3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention; 2. Non-hematological abnormalities: grade 4 non-hematologic AE, grade ≥3 keratopathy. In addition, any other AE that the recruiting Investigators and Sponsor deemed to be dose limiting, regardless of its grade, was also considered as DLT.
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks)
- Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry(From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks)
- Progression-free Survival (PFS)(From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C))
- Disease Control Rate (DCR)(From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C))
- Duration of Response (DOR)(From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C))
- Number of Participants With Treatment-emergent Anti-therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine(From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration [maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)])
- Cohort C: Maximum Concentration Observed After Infusion (Cmax) of Tusamitamab Ravtansine(Cycle 1: Day 1: Start of infusion, end of infusion, 3, 72, 168, and 336 hours post-start of infusion (cycle duration: 28 days))
- Cohort C: Area Under the Plasma Concentration Versus Time Curve Calculated Using the Trapezoidal Method From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine(Cycle 1: Day 1: Start of infusion, end of infusion, 3, 72, 168, and 336 hours post-start of infusion (cycle duration: 28 days))
- Cohort C: Total Body Clearance From Plasma (CL) of Gemcitabine(Cycle 1: Days 1 and 8: Start of infusion, end of infusion, 0.25, 1, 1.5, and 2 hours post-start of infusion (cycle duration: 28 days))
- Cohort C: Cmax of Gemcitabine Metabolite (dFdU)(Cycle 1: Days 1 and 8: Start of infusion, end of infusion, 0.25, 1, 1.5, and 2 hours post-start of infusion (cycle duration: 28 days))