Neoadjuvant Botensilimab and Balstilimab for the Treatment of Advanced Resectable Colorectal Cancer NEST3 (NEST3)
A Phase II Novel Exploratory Study to Test Neoadjuvant Immunotherapy Combinations in Patients With Resectable Colon Cancer (NEST3)
Descripción general del estudio
Estado
Condiciones
- Adenocarcinoma de colon avanzado
- Cáncer de colon en estadio IIIA AJCC v8
- Cáncer de recto en estadio IIIA AJCC v8
- Cáncer de colon en estadio IIIB AJCC v8
- Cáncer de recto en estadio IIIB AJCC v8
- Cáncer de colon en estadio IIIC AJCC v8
- Cáncer de recto en estadio IIIC AJCC v8
- Cáncer de recto en estadio IIB AJCC v8
- Cáncer de recto en estadio IIC AJCC v8
- Adenocarcinoma colorrectal avanzado
- Cáncer de colon en estadio IIB AJCC v8
- Cáncer de colon en estadio IIC AJCC v8
- Adenocarcinoma rectal avanzado
Descripción detallada
PRIMARY OBJECTIVE:
I. To estimate the two-year disease-free survival (DFS) rate when treating advanced mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer with botensilimab (BOT)/balstilimab (BAL) followed by surgery.
SECONDARY OBJECTIVES:
I. To determine the major pathologic response rate for patients with advanced mismatch repair proficient or microsatellite stable (pMMR or MSS) colorectal cancer treated with botensilimab (BOT) + balstilimab (BAL) followed by surgery.
II. To evaluate the safety of treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery.
III. To estimate the pathologic response rate when treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery.
IV. To estimate the three-year disease-free survival rate when treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery.
V. To estimate the median recurrence free survival in patients with advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery, among patients who are disease free at the time of surgery.
VI. To describe the proportion of patients that get all four doses of BAL. VII. To describe the quality of life of patients with advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery.
VIII. To describe the time to surgery after treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery.
IX. To describe the percent of pMMR/MSS colorectal cancer patients treated with BOT/BAL followed by surgery in which adjuvant therapy is recommended, amount and type received, as well as patient refusal rate.
EXPLORATORY OBJECTIVES:
I. To examine changes in tumor microenvironment in response to BOT/BAL when treating advanced pMMR/MSS colorectal cancer.
II. To explore the serial changes in circulating tumor deoxyribonucleic acid (ctdna) when treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery.
III. To explore markers on baseline imaging that correlate with response and long-term outcomes.
IV. To determine ctDNA and cell free deoxyribonucleic acid (cfDNA) detectability before, during and after neoadjuvant BOT/BAL and curative-intent surgical resection.
V. To describe the association between detectable ctDNA and cfDNA measured before, during and after neoadjuvant post-neoadjuvant treatment and surgery with DFS and pathologic response.
VI. To describe the difference in time between ctDNA and cfDNA detection (molecular recurrence) and radiographic evidence of disease recurrence following definitive treatment among patients who achieved undetectable ctDNA and/or cfDNA levels after surgery.
VII. Among patients that get presurgical standard of care (SOC) imaging, to describe the presurgical radiologic response.
OUTLINE:
Patients receive botensilimab intravenously (IV), over 30 minutes, on day 1 and balstilimab IV, over 30 minutes, on days 1, 15, 29 and 43 in the absence of disease progression or unacceptable toxicity. 5-16 weeks later, patients then undergo standard of care resection surgery. Patients undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 2 weeks, 4 weeks and every 3 months for 2 years then every 6 months for 1 year.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Sebastian Perez
- Número de teléfono: 6262184357
- Correo electrónico: sebperez@coh.org
Ubicaciones de estudio
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Arizona
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Goodyear, Arizona, Estados Unidos, 85338
- Reclutamiento
- CTCA at Western Regional Medical Center
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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California
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Corona, California, Estados Unidos, 92882
- Reclutamiento
- City of Hope Corona
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Duarte, California, Estados Unidos, 91010
- Reclutamiento
- City of Hope Medical Center
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Huntington Beach, California, Estados Unidos, 92648
- Reclutamiento
- City of Hope Seacliff
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Irvine, California, Estados Unidos, 92618
- Reclutamiento
- City of Hope at Irvine Lennar
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Long Beach, California, Estados Unidos, 90813
- Reclutamiento
- City of Hope at Long Beach Elm
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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South Pasadena, California, Estados Unidos, 91030
- Reclutamiento
- City of Hope South Pasadena
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Upland, California, Estados Unidos, 91786
- Reclutamiento
- City of Hope Upland
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Georgia
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Newnan, Georgia, Estados Unidos, 30265
- Reclutamiento
- City of Hope Atlanta Cancer Center
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Reclutamiento
- City of Hope at Illinois Chicago Downtown
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Zion, Illinois, Estados Unidos, 60099
- Reclutamiento
- City of Hope at Chicago
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Investigador principal:
- Pashtoon M. Kasi
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Contacto:
- Pashtoon M. Kasi
- Número de teléfono: 949-671-4673
- Correo electrónico: kasi@coh.org
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
Documented informed consent of the participant and Legally Authorized Representative (when applicable)
- Assent, when appropriate, will be obtained and documented for adults lacking capacity per institutional guidelines
- Agreement to allow the use of tissue from past and future surgery and standard of care biopsies
- Age: ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Histologically confirmed or cytologically confirmed colorectal adenocarcinoma. Patients with high grade dysplasia on histology plus unequivocal endoscopic or radiological evidence of invasive cancer are eligible.
Patients diagnosed with rectal cancer who will be treated like colon cancer with curative-intent surgery first and no radiation are also eligible, including:
- Upper rectum or rectosigmoid considered as non-rectal and not undergoing neoadjuvant treatment
- The tumor component should not extend to less 12 cm from the anal verge.
Any patient with rectal cancer for whom radiotherapy is not advised is included in this protocol (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation)
- Microsatellite stability by mismatch repair by immunohistochemistry, polymerase chain reaction and/or other Clinical Laboratory Improvement Amendments (CLIA) certified next generation sequencing. Only patients with mismatch repair proficient or microsatellite stable (pMMR/MSS) tumors are allowed to enroll in the study
- Candidate for and planning a curative resection. Must have surgeon identified
- T4, N+ (American Joint Committee on Cancer [AJCC] TNM staging criteria), or both by central radiographic assessment.
Note: Patients with T3N0 stage IIA are excluded. Stage IIB, IIC, IIIA, IIIB, and IIIC are included. Patients with stage IV disease are excluded
- Absolute neutrophil count (ANC) ≥ 1,500/mm^3
- Platelets ≥ 75,000/mm^3
NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
- Hemoglobin ≥ 8 g/dL
NOTE: Red blood cell transfusions are permitted. Patients should not have active clinically significant bleeding requiring regular transfusions. Iron infusions are also allowed
- Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease, in which case the liver function tests must meet the other eligibility in the protocol)
- Aspartate aminotransferase (AST) ≤ 3.0 x ULN
- Alanine aminotransferase (ALT) ≤ 3.0 x ULN
- Creatinine clearance of ≥ 40 mL/min per the Cockcroft-Gault formula
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 9 months for women, and at least 6 months for men, after the last dose of oxaliplatin therapy. If patients discontinue oxaliplatin more than 9 months (females) or 6 months (males) before discontinuation of balstilimab and/or botensilimab, females and males of childbearing potential must use an effective method of birth control or abstain from sexual activity for the course of the study through at least 120 days after the last dose of balstilimab and/or botensilimab.
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).
- The following are acceptable birth control methods for this study: Surgical sterilization (tubal ligation or hysterectomy for women, or vasectomy for men), double-barrier methods (i.e. condoms, diaphragm, cervical cap, or sponge, used together with spermicidal gel or foam), intrauterine device (IUD) (i.e. Progestin, Copper), or hormonal contraceptives (birth control patches, implants, pills, rings, or injections)
Exclusion Criteria:
Any treatment for colorectal cancer prior to enrollment that includes (but not limited to) chemotherapy, surgery, radiation, immunotherapy and/or biological therapy.
- Note: Surgical intervention e.g. a diverting ostomy to relieve an obstruction from colorectal cancer, those patients will be allowed to enter the study as long as no distant metastatic disease
- Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
- Prior allogeneic organ transplantation
- Herbal medications that require a prescription or are anti-cancer
- Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Please note: patients with more than 1 colorectal cancer tumor at diagnosis (as long as no stage IV disease) are allowed to participate. Pathologic response to each of the tumors will be examined
- Active acute colonic obstruction. Patients whose obstruction is relieved by a successful defunctioning stoma are allowed once recovered to a fitness level consistent with the other eligibility criteria
- Clinically significant uncontrolled illness
- Females only: Pregnant or breastfeeding
- Prior allergic reaction or hypersensitivity to any of the study drug components
- Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs (excluding hypothyroidism, vitiligo, and psoriasis that is controlled with topical management)
- History or current evidence of any condition, co-morbidity, therapy, that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
- Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) are eligible. Serological testing for HIV at screening is not required
- Uncontrolled infection with hepatitis B virus. Patients who are receiving or who have received anti-HBV therapy are eligible. Serological testing for HBV at screening is not required
- Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible. Serological testing for HCV at screening is not required
- Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Treatment (botensilimab and balstilimab)
Patients receive botensilimab IV, over 30 minutes, on day 1 and balstilimab IV, over 30 minutes, on days 1, 15, 29 and 43 in the absence of disease progression or unacceptable toxicity.
5-16 weeks later, patients then undergo standard of care resection surgery.
Patients undergo CT scan and/or MRI and blood sample collection throughout the study.
|
Someterse a una resonancia magnética
Otros nombres:
Someterse a la recolección de muestras de sangre
Otros nombres:
Someterse a una tomografía computarizada
Otros nombres:
Dado IV
Otros nombres:
Dado IV
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Two-year disease-free survival rate
Periodo de tiempo: At 2 years post enrollment
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Defined as the percentage of patients that remain free from any signs of colon cancer at two years post-enrollment.
Will be compared to the historical control rate of 76.8% (from the FoXTROT adjuvant chemotherapy arm) using a one-sided, one-sample log-rank test.
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At 2 years post enrollment
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Major pathologic response rate
Periodo de tiempo: Up to 3 years
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Defined as the proportion of patients achieving major pathologic responses defined as either a >= 90% tumor reduction or 100% reduction (near complete response + pathologic complete response).
Will be compared with the historical control rate of 10% using a one-sided, continuity corrected Z-test.
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Up to 3 years
|
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Incidence of adverse events
Periodo de tiempo: Up to 3 years
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Assessed according to Common Terminology Criteria for Adverse Events version 6.0.
Will be summarized using descriptive statistics.
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Up to 3 years
|
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Pathologic response rate
Periodo de tiempo: Up to 3 years
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Defined as the proportion of patients achieving a pathologic response, defined as a ≥ 50% tumor reduction.
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Up to 3 years
|
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Three-year disease-free survival rate
Periodo de tiempo: At 3 years post-enrollment
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Defined as the percentage of patients that remain free from any signs of colon cancer at three years post-enrollment.
Will be summarized similar to 2-year survival but at the 3-year mark.
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At 3 years post-enrollment
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Recurrence free survival
Periodo de tiempo: Time from surgery to date of first cancer recurrence or death as a result of any cause, whichever occurs first, up to 3 years
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Assessed among patients that are disease free at the time of surgery.
Will be graphically represented using Kaplan-Meier methods and summarized using descriptive statistics.
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Time from surgery to date of first cancer recurrence or death as a result of any cause, whichever occurs first, up to 3 years
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Number of patients who get all four doses of balstilimab divided by number of enrolled patients
Periodo de tiempo: Up to 3 months
|
Will be summarized using descriptive statistics.
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Up to 3 months
|
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Change in Eastern Cooperative Oncology Group
Periodo de tiempo: Up to 3 years
|
Will be summarized using descriptive statistics.
|
Up to 3 years
|
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Time to surgery
Periodo de tiempo: Up to 9 months
|
Will be summarized using descriptive statistics.
|
Up to 9 months
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Proportion of patients in which adjuvant therapy is recommended, of these the percent who refuse adjuvant therapy
Periodo de tiempo: Up to 9 months
|
Will be summarized using descriptive statistics.
|
Up to 9 months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Pashtoon M Kasi, City of Hope Medical Center
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Enfermedades intestinales
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Neoplasias colorrectales
- Neoplasias Intestinales
- Enfermedades Rectales
- Enfermedades del Colon
- Neoplasias Rectales
- Neoplasias colónicas
- Técnicas de investigación
- Técnicas de laboratorio clínico
- Técnicas y procedimientos de diagnóstico
- Diagnóstico
- Técnicas de química, analítica
- Análisis de espectro
- Manejo de muestras
- Espectroscopía de resonancia magnética
- balstilimab
Otros números de identificación del estudio
- 25964 (Otro identificador: City of Hope Medical Center)
- P30CA033572 (Subvención/contrato del NIH de EE. UU.)
- NCI-2026-02923 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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