NCT06843434招募中2 期
A Phase II Study of Neoadjuvant Botensilimab and Balstilimab Immunotherapy for Mismatch Repair Proficient Rectal Adenocarcinoma
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 14
- 主要终点
- Best Overall Response Rate
研究概览
简要总结
The purpose of this study is to find out whether the combination of botensilimab and balstilimab (BOT/BAL) is a safe and effective treatment that causes few or mild side effects for people with mismatch repair proficient (MMRp)/microsatellite stable (MSS) locally advanced rectal adenocarcinoma. The investigators will also find out whether BOT/BAL is an effective treatment when given in combination with standard chemotherapy.
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
- •Willing and able to provide written informed consent for trial.
- •a. If participant is unable to provide written informed consent, the legally authorized representative (LAR) of the person who is being asked to participate in this research study may give consent on the participant's behalf.
- •Be ≥18 years of age on the date of signing informed consent.
- •ECOG performance status of 0 or
- •Histologically confirmed rectal adenocarcinoma.
- •Adenocarcinoma with distal margin of 15 cm or less from the anal verge on endoscopy, staged with endorectal ultrasound (ERUS) or magnetic resonance imaging (MRI) as cT3/cT4 N0 or cT(any) cN1/
- •No evidence of distant metastases
- •Radiologically measurable or clinically evaluable disease per Protocol Section 13.
- •Tumor specimen that demonstrates intact mismatch repair enzymes by immunohistochemistry or microsatellite stability as demonstrated by NGS or PCR.
- •Negative pregnancy test done within 14 days prior to beginning treatment, for women of childbearing potential only. Subjects of childbearing potential must be willing to use an adequate method of contraception. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom). Contraception is required for the course of the study starting with the first dose of study medication through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- •Nonchildbearing potential is defined as follows (by other than medical reasons):
- •≥45 years of age and has not had menses for >1 year
- •Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
- •Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study.
- •Demonstrate adequate organ function as defined in the Table 6-1 below within 28 days of Cycle 1 Day 1, and all screening labs should be performed within 28 days of treatment initiation.
- •Hematological Absolute neutrophil count (ANC): ≥1,500 /mm^3 Platelets: ≥100,000 / mcL Hemoglobin: ≥8.0 g/dL
- •Renal Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≤1.5 × upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 × institutional ULN AST (SGOT) and ALT (SGPT): ≤ 2.5 × ULN
- •Coagulation International normalized ratio (INR) or Prothrombin time (PT) or activated partial thromboplastin time (aPTT): For patients not taking warfarin: INR ≤ 1.5 or PT ≤ 1.5 x ULN; and either PTT or aPTT ≤ 1.5 x ULN. Patients on warfarin may be included on a stable dose with a therapeutic INR <3.5
排除标准
- •Recurrent rectal cancer.
- •Prior pelvic radiation therapy, chemotherapy, or surgery for rectal cancer.
- •Tumor is causing symptomatic bowel obstruction (patients who have a temporary diverting ostomy are eligible).
- •Other invasive malignancy ≤ 2 years prior to registration. Exceptions are non-melanoma skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma.
- •Active infection requiring systemic therapy.
- •Other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
- •Known history of interstitial lung diseases/pneumonitis
- •Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- •Known active hepatitis B (e.g., HbsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected).
- •Live vaccination within 28 days prior to receiving the first dose of immunotherapy. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction.
- •Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster < 7 days before C1D
- •For vaccines requiring more than 1 dose, the full series should be completed prior to C1D1, when feasible. Booster shot not required but also must be administered > 7 days from C1D1 or > 7 days from future cycle on study
- •Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 180 days of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication.
- •a. QTcF (QT interval corrected using Fridericia's formula) of ≥450 ms.
- •Known active tuberculosis.
- •Receiving systemic corticosteroid therapy 1 week prior to the first dose of study drug or receiving any other form of systemic immunosuppressive medication.
- •a. Corticosteroid use as a premedication for IV contrast allergies/reactions is allowed. Subjects who are receiving daily corticosteroid replacement therapy are also an exception to this rule. Daily prednisone at doses of ≤ 7.5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy. Use of inhaled or topical corticosteroids is permitted.
- •Has ongoing or recent (within 5 years) evidence of significant autoimmune disease or any other condition that required treatment with systemic immunosuppressive treatments. The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement.
- •Prior allogeneic tissue/solid organ transplant, except for corneal transplants.
研究组 & 干预措施
Participants with locally advanced rectal cancer
Experimental
Up to 40 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) locally advanced (stage II or III) rectal cancer
干预措施: Balstilimab (Drug)
Participants with locally advanced rectal cancer
Experimental
Up to 40 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) locally advanced (stage II or III) rectal cancer
干预措施: Botensilimab (Drug)
结局指标
主要结局
Best Overall Response Rate
时间窗: 1 year
The primary objective of this study is to determine the best overall response rate (ORR) after initial neoadjuvant combination botensilimab and balstilimab in subjects with MMRp/MSS locally advanced (stage II or III) rectal adenocarcinoma. ORR is defined by rectal MRI and endoscopic exam and graded as progressive disease (PD), stable disease (SD) (sustained for 3 months), partial response (PR), near complete response (nCR) and clinical complete response (cCR). Patients with PR, nCR, or cCR will be considered responders, while the rest will be non-responders.
次要结局
未报告次要终点
研究者
研究点 (14)
Loading locations...
相似试验
招募中
1 期
Botensilimab Plus Balstilimab and Fasting Mimicking Diet Plus Vitamin C for Patients With KRAS-Mutant Metastatic Colorectal CancerNCT06336902University of Southern California15
撤回
2 期
Botensilimab, Balstilimab and Regorafenib or Botensilimab and Balstilimab for the Treatment of Advanced or Metastatic Microsatellite Stable Colorectal CancerAdvanced Colon AdenocarcinomaAdvanced Colorectal AdenocarcinomaAdvanced Rectal AdenocarcinomaMetastatic Colon AdenocarcinomaMetastatic Colorectal AdenocarcinomaMetastatic Rectal AdenocarcinomaStage III Colon Cancer AJCC v8Stage III Colorectal Cancer AJCC v8Stage III Rectal Cancer AJCC v8Stage IV Colon Cancer AJCC v8Stage IV Colorectal Cancer AJCC v8Stage IV Rectal Cancer AJCC v8NCT06575725City of Hope Medical Center84
进行中（未招募）
1 期
Botensilimab, Balstilimab and Regorafenib for the Treatment of Patients With Microsatellite Stable Metastatic Colorectal Cancer Who Have Progressed on Prior ChemotherapyAdvanced Colorectal AdenocarcinomaAdvanced Microsatellite Stable Colorectal CarcinomaMetastatic Colorectal AdenocarcinomaMetastatic Microsatellite Stable Colorectal CarcinomaNCT05672316City of Hope Medical Center28
进行中（未招募）
2 期
Assessment of the Safety and Efficacy of Balstilimab in Combination With Botensilimab for the Treatment of Non-Small Cell Lung Cancer (IMMONC0008)Non-small Cell Lung CancerNCT06322108Immune Oncology Research Institute45
已完成
1 期
Phase I/II Study of Bosutinib in Combination With Inotuzumab Ozogamicin in CD22-positive PC Positive ALL and CMLB Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveBlasts More Than 5 Percent of Bone Marrow Nucleated CellsCD22 PositivePhiladelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous LeukemiaRecurrent Chronic Myelogenous Leukemia, BCR-ABL1 PositiveRefractory Chronic Myelogenous Leukemia, BCR-ABL1 PositiveNCT02311998M.D. Anderson Cancer Center22