A Phase 2 Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy for Resectable Esophageal and Gastroesophageal Junction Cancers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 10
- 主要终点
- Pathologic Complete Response (pCR) Rate (%) Overall
研究概览
简要总结
This pilot phase II trial studies the therapeutic effects and side effects of CD40 agonistic monoclonal antibody APX005M when combined with chemotherapy and radiation therapy, and to see how well they work to reduce or remove esophageal or gastroesophageal (GE) cancers when given before surgery in treating patients with esophageal cancer or GE cancer than can be removed by surgery. APX005M is intended to stimulate the body's own immune system so that the immune cells can more effectively invade and destroy the tumor, adding to the benefits of the chemotherapy and radiation therapy. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving APX005M, chemotherapy, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
详细描述
Primary Objective:
To assess the efficacy of this novel combination, as measured by the pathologic complete response (pCR) rate.
Secondary Objectives:
- To further characterize the safety and feasibility of combining APX005M with SOC chemoradiation (external beam radiation in daily fractions, with concurrent weekly low-dose carboplatin/paclitaxel) in the neoadjuvant setting for patients with resectable esophageal and GE junction cancers.
- To assess the efficacy of combining APX005M with SOC chemoradiation as measured by rates of R0 resection (microscopically negative margins, i.e., no tumor remains following surgery); and radiographic/metabolic response to neoadjuvant treatment on CT-PET.
Exploratory Objectives:
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years of age.
- •Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the esophagus or GE junction.
- •Surgically resectable (T1-3 Nx preferably by endoscopic ultrasound [EUS]). (Excluded: T1N0 tumors, cervical esophageal location, tumors invading the tracheobronchial tree or with fistula, distant disease that cannot be included in the radiation field or be resected at the time of esophagectomy).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Adequate hematological, renal, and hepatic parameters.
排除标准
- •Any history of or current hematologic malignancy.
- •History of a second primary cancer is allowed in the event the cancer is curatively resected and there is no evidence of recurrence/metastatic disease x 1 year. Subjects who have a history of cervical or breast carcinoma in situ, localized prostate cancer, adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder tumors [Ta, Tis & T1] are also allowed.
- •Major surgery within 4 weeks of first dose of investigational product.
- •Prior or concurrent treatment with any anticancer agent for the same cancer diagnosis.
- •Prior exposure to any immuno-oncology agents, including CD40/PD-1/PD-L1/CTLA-4 inhibitors (if any ambiguity, should be discussed with study principal investigator).
- •History of bone marrow transplantation.
- •History of autoimmune disorders with the exception of vitiligo or autoimmune thyroid disorders.
- •Chronic steroid dependency (prednisone equivalent > 10 mg/day). Any steroid use should be discontinued at least 2 weeks prior to initiation of study treatment.
- •Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months before first dose.
- •Known human immunodeficiency virus (HIV) infection.
研究组 & 干预措施
APX005M With Standard of Care Chemoradiation
Participants will receive standard of care chemoradiation, consisting of:
- External beam radiation in daily fractions (28 fractions) from Weeks 1-6, administered once per day up to 5 days/week.
- Carboplatin (area under the carboplatin plasma concentration versus time curve = 2) and paclitaxel (50 mg/m^2) chemotherapy intravenously (IV) over 1 hour, once weekly, from Weeks 1-5.
The participants also will receive concurrent 0.3 mg/kg APX005M IV over 1 hour, once weekly, on Weeks 1, 2, 4, and 6 (2-3 days after chemoradiation).
Surgical resection of the tumor will be planned from Week 10 up to approximately Week 17, as indicated in the protocol amendment under which each participant is enrolled.
干预措施: APX005M (Drug)
APX005M With Standard of Care Chemoradiation
Participants will receive standard of care chemoradiation, consisting of:
- External beam radiation in daily fractions (28 fractions) from Weeks 1-6, administered once per day up to 5 days/week.
- Carboplatin (area under the carboplatin plasma concentration versus time curve = 2) and paclitaxel (50 mg/m^2) chemotherapy intravenously (IV) over 1 hour, once weekly, from Weeks 1-5.
The participants also will receive concurrent 0.3 mg/kg APX005M IV over 1 hour, once weekly, on Weeks 1, 2, 4, and 6 (2-3 days after chemoradiation).
Surgical resection of the tumor will be planned from Week 10 up to approximately Week 17, as indicated in the protocol amendment under which each participant is enrolled.
干预措施: Radiation Therapy (Radiation)
APX005M With Standard of Care Chemoradiation
Participants will receive standard of care chemoradiation, consisting of:
- External beam radiation in daily fractions (28 fractions) from Weeks 1-6, administered once per day up to 5 days/week.
- Carboplatin (area under the carboplatin plasma concentration versus time curve = 2) and paclitaxel (50 mg/m^2) chemotherapy intravenously (IV) over 1 hour, once weekly, from Weeks 1-5.
The participants also will receive concurrent 0.3 mg/kg APX005M IV over 1 hour, once weekly, on Weeks 1, 2, 4, and 6 (2-3 days after chemoradiation).
Surgical resection of the tumor will be planned from Week 10 up to approximately Week 17, as indicated in the protocol amendment under which each participant is enrolled.
干预措施: Paclitaxel (Drug)
APX005M With Standard of Care Chemoradiation
Participants will receive standard of care chemoradiation, consisting of:
- External beam radiation in daily fractions (28 fractions) from Weeks 1-6, administered once per day up to 5 days/week.
- Carboplatin (area under the carboplatin plasma concentration versus time curve = 2) and paclitaxel (50 mg/m^2) chemotherapy intravenously (IV) over 1 hour, once weekly, from Weeks 1-5.
The participants also will receive concurrent 0.3 mg/kg APX005M IV over 1 hour, once weekly, on Weeks 1, 2, 4, and 6 (2-3 days after chemoradiation).
Surgical resection of the tumor will be planned from Week 10 up to approximately Week 17, as indicated in the protocol amendment under which each participant is enrolled.
干预措施: Carboplatin (Drug)
APX005M With Standard of Care Chemoradiation
Participants will receive standard of care chemoradiation, consisting of:
- External beam radiation in daily fractions (28 fractions) from Weeks 1-6, administered once per day up to 5 days/week.
- Carboplatin (area under the carboplatin plasma concentration versus time curve = 2) and paclitaxel (50 mg/m^2) chemotherapy intravenously (IV) over 1 hour, once weekly, from Weeks 1-5.
The participants also will receive concurrent 0.3 mg/kg APX005M IV over 1 hour, once weekly, on Weeks 1, 2, 4, and 6 (2-3 days after chemoradiation).
Surgical resection of the tumor will be planned from Week 10 up to approximately Week 17, as indicated in the protocol amendment under which each participant is enrolled.
干预措施: Surgical resection of tumor (Procedure)
结局指标
主要结局
Pathologic Complete Response (pCR) Rate (%) Overall
时间窗: At time of surgery, up to a maximum of 261 days
The pCR was defined as post-neoadjuvant pathologic tumour, node, metastasis (ypTNM) (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. * T0: No evidence of primary tumor. * N0: Cancer has not spread to nearby lymph nodes. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
pCR Rate (%) by Baseline Tumor Location Subgroup
时间窗: At time of surgery, up to a maximum of 261 days
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
pCR Rate (%) by Steroid Use Subgroup
时间窗: At time of surgery, up to a maximum of 261 days
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. Steroids use: Yes was defined as participants with any steroid (ATC2 class corticosteroids for systemic use) from within 30 days of the first dose of sotigalimab to up to 7 days after the first dose and participants not fulfilling previous requirements are defined as Steroids use: No. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
pCR Rate (%) by Baseline Histologic Subgroup
时间窗: At time of surgery, up to a maximum of 261 days
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
pCR Rate (%) by Surgery Subgroup
时间窗: At time of surgery, up to a maximum of 261 days
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. The subgroup of participants who had surgery before or at 16/17 weeks were defined as start of study treatment to surgery date from the surgical resection form, less than or equal to 17 weeks (119 days = 17 weeks \* 7 days) or participants who were scheduled to have surgery but had their procedure aborted due to progressive disease at the time of the procedure or immediately before and did not have surgery because of metastasis. The subgroup of participants who had surgery after Week 17 were defined as start of study treatment to surgery date from the surgical resection form, greater than 17 weeks. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
次要结局
- Radiographic/Metabolic Response to Neoadjuvant Treatment on CT-PET by Baseline Tumor Location Subgroup(At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to approximately 20 weeks)
- Rate (%) of R0 Resection by Baseline Histologic Subgroup(At time of surgery, up to a maximum of 261 days)
- Rate (%) of R0 Resection Overall(At time of surgery, up to a maximum of 261 days)
- Pathologic Stage at Time of Surgery(At time of surgery, up to a maximum of 261 days)
- Radiographic/Metabolic Response to Neoadjuvant Treatment on CT-PET by Baseline Histologic Subgroup(At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively))
- Radiographic/Metabolic Response to Neoadjuvant Treatment on Computed Tomography (CT)/CT-Positron Emission Tomography (PET) (CT-PET) Overall(At time of surgery, up to a maximum of 261 days, 3 and 6 months post-operatively, and End of Study Visit (maximum of 6 months post-operatively))