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.
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. III. Evaluate the feasibility and timing of generating STIL101 for injection. IV. Describe STIL101 cell count in patients with respect to baseline characteristics, clinical outcome and adverse events. EXPLORATORY OBJECTIVE: I. Biological correlatives associated with STIL101 for injection creation and infusion. OUTLINE: 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 intravenously (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 subcutaneously (SC) once daily (QD) on day 0 for up to 6-10 days. Additionally, patients undergo blood sample collection, biopsy, computed tomography (CT) and optional magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up at days 42, 56, 70 and 84 then every 2-4 weeks up to week 96 or progression. Patients who discontinued treatment are followed up every 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given SC
Undergo biopsy
Undergo blood sample collection
Undergo CT
Given IV
Undergo excisional biopsy
Given IV
Undergo MRI
Receive standard of care therapy
Given STIL101 for injection IV
Infusion limiting toxicities (ILTs)
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.
Time frame: From the start of STIL101 for injection up to 28 days
Treatment-related adverse events (AEs)
Assessed by NCI CTCAE v 5.0. AEs will be summarized by severity, grade and attribution.
Time frame: Up to 2 years
Overall response rate (ORR)
The proportion of subjects with confirmed complete response (CR) / immune related (i)CR or partial response (PR) / iPR will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Immune-Modified (i)RECIST 1.0.
Time frame: Up to 2 years
Disease control rate
The proportion of subjects who achieve CR/iCR, PR/iPR or maintain at least stable disease will be assessed using RECIST 1.1/iRECIST 1.0.
Time frame: From start of STIL101 for injection infusion for at least one post-treatment scan up to 2 years
Overall survival
Analysis will be descriptive.
Time frame: From the start of STIL101 for injection until death due to any cause up to 2 years
Overall survival
Analysis will be descriptive.
Time frame: From excisional biopsy until death due to any cause up to 2 years
Progression-free survival
Analysis will be descriptive.
Time frame: 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
Analysis will be descriptive.
Time frame: Up to 2 years
Time to lymphodepleting chemotherapy
Analysis will be descriptive.
Time frame: From subject informed consent to start of lymphodepleting chemotherapy up to 2 years
Excisional biopsy complication rate
Analysis will be descriptive.
Time frame: Up to 2 years
STIL101 for injection generation times
Analysis will be descriptive.
Time frame: Up to 2 years
Successful STIL101 for injection generation and administration
Success rate for generation will be summarized and causes of failure will be documented. Those unable to receive STIL101 for injection will also be summarized.
Time frame: Up to 2 years
STIL101 cell count
STIL101 cell count in patients with respect to baseline characteristics, clinical outcome and AEs will be described.
Time frame: Up to 2 years
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