A Phase 1 Safety and Efficacy Study of STIL101 for Injection in Locally Advanced, Unresectable, or Metastatic Pancreatic Ductal Adenocarcinoma, Colorectal Cancer, Renal Cell Carcinoma, Cervical Cancer, and Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 12
- 主要终点
- Infusion limiting toxicities (ILTs)
研究概览
简要总结
This phase I trial tests the safety and side effects of STIL101 for injection and how well it works in treating patients with pancreatic cancer, colorectal cancer (CRC), renal cell cancer (RCC), cervical cancer (CC) and melanoma that has spread to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). STIL101 for injection, an autologous (made from the patients own cells) cellular therapy, is made up of specialized white blood cells called lymphocytes or "T cells" collected from a piece of the patients tumor tissue. The T cells collected from the tumor are then grown in a laboratory to create STIL101 for injection. STIL101 for injection is then given to the patient where it may attack the tumor. Giving chemotherapy, such as cyclophosphamide and fludarabine, helps prepare the body to receive STIL101 for injection in a way that allows the T cells the best opportunity to attack the tumor. Aldesleukin is a form of interleukin-2, a cytokine made by leukocytes. Aldesleukin increases the activity and growth of white blood cells called T lymphocytes and B lymphocytes. Giving STIL101 for injection may be safe, tolerable and/or effective in treating patients with locally advanced, metastatic or unresectable pancreatic cancer, CRC, RCC, CC and melanoma.
详细描述
PRIMARY OBJECTIVE:
I. Determine the safety of administering STIL101 for injection in subjects with locally advanced, unresectable, or metastatic pancreatic ducal adenocarcinoma (PDAC), CRC, RCC CC or melanoma.
SECONDARY OBJECTIVES:
I. Summarize the efficacy observed due to STIL101 for injection in patients with locally advanced, unresectable or metastatic PDAC, CRC, RCC, CC or melanoma:
Ia. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Immune-Modified (i)RECIST 1.0; Ib. Disease control rate (DCR) as measured from STIL101 infusion; Ic. Overall survival (OS) as measured from STIL101 infusion; Id. Progression-free survival (PFS) as measured from STIL101 infusion. II. Summarize pre-STIL101 for injection therapy and outcomes from first study-related procedure.
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
- •Documented informed consent of the participant and/or legally authorized representative.
- •Assent, when appropriate, will be obtained per institutional guidelines
- •Agree to research biopsies while on-study
- •Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening, while the request for a translated full consent is processed
- •Age: ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) ≤ 1
- •Anticipated life expectancy of > 6 months at the time of enrollment
- •Participants with pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CC), renal cell carcinoma (RCC), cervical cancer (CC) and melanoma, meeting the following criteria will be eligible:
- •Cytologically or histologically confirmed locally advanced, unresectable, or metastatic PDAC, CRC, RCC, CC, melanoma
- •Patients must have received at least 1 line of standard therapy prior to receiving STIL101 for injection. Note: Patients may be enrolled prior to starting treatment to harvest tumor and blood samples for tumor infiltrating lymphocyte (TIL) generation
- •For pancreatic cancer patients:
- •Patients on first line treatment will need to receive at least 4 months of standard chemotherapy before receiving STIL101 for injection
- •In the second line setting, these patients may opt to receive STIL101 for injection at any time
- •For melanoma cancer patients: Patients need to have received prior PD1 therapy and BRAF inhibitor treatment in patients with a V600E mutation
- •For RCC, CRC, CC patients: Patients need to have failed at least 1 line of prior therapy
- •Measurable disease by RECIST 1.1
- •At least one lesion (or aggregate of lesions resected) that can be safety biopsied (excisional) and yield a volume (target of > 1cm^3) to generate STIL101 for injection (principal investigator [PI] discretion)
- •Absolute neutrophil count (ANC) ≥ 1,000/mm^3
- •NOTE: Growth factor is not permitted within 14 days of screening ANC assessment
- •Platelets ≥ 100,000/mm^3
- •NOTE: Platelet transfusions are not permitted within 14 days of screening platelet assessment
- •Hemoglobin ≥ 8 g/dL
- •NOTE: Red blood cell transfusions are not permitted within 14 days of screening platelet assessment
- •Total bilirubin ≤ 2 x upper limit of normal (ULN) (unless participant has Gilbert's disease which allows total bilirubin ≤ 3 x ULN)
- •Aspartate aminotransferase (AST) ≤ 3 x ULN; ≤ 5.0 x ULN if hepatic metastases are present
- •Alanine transaminase (ALT) ≤ 3 x ULN; ≤ 5.0 x ULN if hepatic metastases are present
- •Creatinine clearance (CRCl) of ≥ 40 mL/min per 24-hour urine test or the Cockcroft-Gault formula
- •Oxygen (O2) saturation > 92% on room air not requiring oxygen supplementation
- •Note: To be performed within 28 days prior to start of protocol therapy
- •Left ventricular ejection fraction (LVEF) ≥ 50%
- •Note: To be performed within 8 weeks prior to start of protocol therapy
- •If not receiving anticoagulants: International normalized ratio (INR) or prothrombin (PT) ≤ 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
- •If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
- •Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative), and syphilis (RPR)
- •If seropositive for HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetected
- •QuantiFERON-TB Gold or equivalent
- •Results do not impact patient eligibility; however, the test must be initiated prior to enrollment
- •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 6 months after the last dose of protocol therapy
- •Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
排除标准
- •Prior organ transplant
- •Concomitant herbal medications with exception to cannabidiol (CBD), which is allowed
- •Continuous systemic steroid therapy (i.e., > 10 mg/day of prednisone or other steroid equivalent dose) or other immunosuppressive therapies. Physical replacement doses (i.e., adrenocortical insufficiency), inhaled or topical steroids at ≤ 10 mg/day of prednisone or another steroid equivalent dose are permissible in the absence of active auto-immune disease
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents, including history of hypersensitivity to any drugs of the aminoglycoside group
- •Prior or current known uveitis within 6 months of informed consent
- •Active viral, bacterial, or fungal infection requiring treatment. Patients must be seronegative for the human immunodeficiency virus (HIV) and syphilis (RPR). Patients with hepatitis infections are allowed with undetected viral load
- •Primary immunodeficiency (such as severe combined immunodeficiency [SCID] or acquired immunodeficiency syndrome [AIDS])
- •End-stage renal disorder requiring hemodialysis
- •Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
- •Known clinically significant pulmonary conditions within 6 months of informed consent
- •Prior or concurrent malignancy. Prior malignancies with a low probability of recurrence requiring treatment such as the following are allowed: carcinoma in situ of the cervix, nonmelanoma skin cancer and low grade (Gleason score ≤ 6=Gleason group 1) localized prostate cancer. Prior malignancies not listed require PI approval
- •Females only: Pregnant or breastfeeding
- •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)
研究组 & 干预措施
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Aldesleukin (Biological)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Biopsy (Procedure)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Cyclophosphamide (Drug)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Excisional Biopsy (Procedure)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Fludarabine (Drug)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Standard Treatment (Procedure)
Treatment (STIL101 for injection)
Patients undergo excisional biopsy and continue receiving standard of care therapy for 3-4 months prior to the start of study therapy. Patients with successful generation of STIL101 for injection receive cyclophosphamide IV over 2 hours on days -5 to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on day 0 in the absence of disease progression or unacceptable toxicity. Patients also receive aldesleukin SC QD on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, CT and optional MRI throughout the study.
干预措施: Therapeutic Tumor Infiltrating Lymphocytes (Biological)
结局指标
主要结局
Infusion limiting toxicities (ILTs)
时间窗: From the start of STIL101 for injection up to 28 days
Assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. ILTs will be summarized by severity, grade and attribution.
Treatment-related adverse events (AEs)
时间窗: Up to 2 years
Assessed by NCI CTCAE v 5.0. AEs will be summarized by severity, grade and attribution.
次要结局
- Overall response rate (ORR)(Up to 2 years)
- Disease control rate(From start of STIL101 for injection infusion for at least one post-treatment scan up to 2 years)
- Overall survival(From excisional biopsy until death due to any cause up to 2 years)
- Progression-free survival(From start of STIL101 for injection infusion until documented progressive disease or death due to any cause up to 2 years)
- Failure to receive STIL101 after excisional biopsy(Up to 2 years)
- Time to lymphodepleting chemotherapy(From subject informed consent to start of lymphodepleting chemotherapy up to 2 years)
- Excisional biopsy complication rate(Up to 2 years)
- STIL101 for injection generation times(Up to 2 years)
- Successful STIL101 for injection generation and administration(Up to 2 years)
- STIL101 cell count(Up to 2 years)