Eftilagimod Alpha in Combination With Neoadjuvant Chemotherapy in Patients With Hormone Receptor Positive/HER2-neg Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- To determine pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) and Efti treatment
研究概览
简要总结
The goal of this interventional study is to determine pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) and Efti treatment. This is a prospective single arm interventional trial in patients with early-stage HR+/HER2 -ve breast cancer (Stage I-III) who are eligible for neoadjuvant chemotherapy (NAC). Enrolled patients will be treated with single agent efti for 3 weeks and then start NAC in combination with efti. There are 2 standard NAC usually used and will be determined by treating physician prior to starting on this trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have histologically documented HR+/HER2 neg (defined as ER expression >10% by IHC and/or PR expression > 10% by IHC and HER2 0 or 1+ or 2+ by IHC or FISH ratio <2 or HER2 gene copy number of <6).
- •Clinical early-stage breast cancer (Stage I-III) and a candidate for NAC.
- •Be informed of the investigational nature of the trial and all pertinent aspects of the trial.
- •Have ECOG performance status of 0-
- •Have the ability to understand and the willingness to sign a written informed -consent document in accordance with institutional and federal guidelines.
- •Be ≥ 21 years of age.
- •Have serum creatinine < 1.5 x institutional upper limit of normal (IULN) or a calculated creatinine clearance ≥ 30ml/min (calculated by Cockcroft Gault equation), bilirubin ≤ 2.0, and an SGOT/SGPT/alkaline phosphatase ≤ 2.0 x IULN.
- •Have adequate bone marrow function (ANC >1000/μL, Platelets >100,000/ml, Hemoglobin >10gm/dL).
- •Women of childbearing potential or male patients of reproductive potential with female partners of childbearing potential must not consider getting pregnant and must avoid pregnancy during the trial and for at least 6 months after the last dose of trial treatment. Female and male patients of reproductive potential must practice highly effective methods of contraception with their partners, if of reproductive potential, during treatment and for 6 months following last dose of treatment with IP.
排除标准
- •Receiving concurrent anti-neoplastic therapy for another malignancy
- •Known documented or suspected hypersensitivity to the components of the trial drug or analogs.
- •Stage IV or patients otherwise not indicated for surgery. Patients with oligometastatic disease who are undergoing curative intent treatment are eligible as long as curative intent surgery is planned.
- •A woman of child-bearing potential who has a positive serum pregnancy test (within 72 hours) prior to Day
- •Breastfeeding
- •Serious infection within 4 weeks prior to Day 1 or active acute or chronic infection needing IV antibiotics. Note: Subjects treated for moderately severe infections with oral antibiotics only, may be included, based on consultation with trial Investigator.
- •Evidence of severe or uncontrolled cardiac disease within 6 months prior to first dose of trial treatment including: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 5.0 Grade ≥ 2, atrial fibrillation > grade 2 not controlled by a pacemaker, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA III-IV), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
- •Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- •Receives continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days prior to Day
- •Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease.
- •Live vaccine within 30 days of planned Day
- •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 (BCG), 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. Note: non-live vaccines (e.g., non-live influenza vaccine, non-live COVID-19 vaccine) can be given until 3 days prior to planned Day
- •Prior anti-LAG-3 therapy (e.g. anti-LAG-3 antibodies).
- •Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
- •Has had an allogenic tissue/solid organ transplant.
研究组 & 干预措施
Efti + NAC Regimens
Eftilagimod Alfa (Efti) will be administered subcutaneously at a dose of 30 mg beginning of week 1 of the trial for a total of 3 doses (week 1, 2 and 3). After 3 weeks, efti will be administered starting with week 4, every 2 weeks and combined with either TC or AC.
NAC regimens:
- Docetaxel-cyclophosphamide (TC) intravenous (i.v) every 3 weeks (q3w) x 4, or
- Dose dense Adriamycin-cyclophosphamide (AC) i.v q2w x 4 followed by weekly paclitaxel IV X12 weeks (alternatively weekly nab-paclitaxel can be used per physician's preference if patient unable to tolerate paclitaxel due to infusion reaction). The NAC regimen will be determined by the treating physician prior to starting on this trial.
干预措施: Eftilagimod Alfa (Efti) (Drug)
Efti + NAC Regimens
Eftilagimod Alfa (Efti) will be administered subcutaneously at a dose of 30 mg beginning of week 1 of the trial for a total of 3 doses (week 1, 2 and 3). After 3 weeks, efti will be administered starting with week 4, every 2 weeks and combined with either TC or AC.
NAC regimens:
- Docetaxel-cyclophosphamide (TC) intravenous (i.v) every 3 weeks (q3w) x 4, or
- Dose dense Adriamycin-cyclophosphamide (AC) i.v q2w x 4 followed by weekly paclitaxel IV X12 weeks (alternatively weekly nab-paclitaxel can be used per physician's preference if patient unable to tolerate paclitaxel due to infusion reaction). The NAC regimen will be determined by the treating physician prior to starting on this trial.
干预措施: Docetaxel-cyclophosphamide (TC) intravenous (i.v) (Drug)
Efti + NAC Regimens
Eftilagimod Alfa (Efti) will be administered subcutaneously at a dose of 30 mg beginning of week 1 of the trial for a total of 3 doses (week 1, 2 and 3). After 3 weeks, efti will be administered starting with week 4, every 2 weeks and combined with either TC or AC.
NAC regimens:
- Docetaxel-cyclophosphamide (TC) intravenous (i.v) every 3 weeks (q3w) x 4, or
- Dose dense Adriamycin-cyclophosphamide (AC) i.v q2w x 4 followed by weekly paclitaxel IV X12 weeks (alternatively weekly nab-paclitaxel can be used per physician's preference if patient unable to tolerate paclitaxel due to infusion reaction). The NAC regimen will be determined by the treating physician prior to starting on this trial.
干预措施: Dose dense Adriamycin-cyclophosphamide (AC) i.v (Drug)
结局指标
主要结局
To determine pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) and Efti treatment
时间窗: From enrollment to the end of the study (5 years)
The number of pathological complete responses determined in surgical pathology report. The primary endpoint is pCR to NAC + efti. Simon's 2-stage design will be used. The null hypothesis that the true pCR rate is 0.08 (8%) will be tested against a one-sided alternative. In the first stage, 30 patients will be accrued. If there are 2 or fewer responses in these 30 patients, the study will be stopped. Otherwise, 20 additional patients will be accrued for a total of 50. The null hypothesis will be rejected if 8 or more responses are observed in 50 patients. This design yields a type I error rate of 0.0426 and power of 0.80 when the true pCR rate is 0.20 (20%).
次要结局
- To determine clinical response to Efti + NAC.(From enrollment to the end of study (5 years))
- To determine change in tumor's Ki67(From enrollment to the end of study (5 years))
研究者
Pavani Chalasani
Professor of Medicine; Director, Division of Hematology Oncology
George Washington University