STIL101 For Injection For The Treatment Of Locally Advanced, Metastatic Or Unresectable Pancreatic Cancer, Colorectal Cancer, Renal Cell Cancer, Cervical Cancer And Melanoma

Study Overview

STIL101 for Injection for the Treatment of Locally Advanced, Metastatic or Unresectable Pancreatic Cancer, Colorectal Cancer, Renal Cell Cancer, Cervical Cancer and Melanoma

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.

Locally Advanced Cervical Carcinoma
Locally Advanced Colorectal Carcinoma
Locally Advanced Malignant Solid Neoplasm
Locally Advanced Melanoma
Locally Advanced Pancreatic Ductal Adenocarcinoma
Locally Advanced Renal Cell Carcinoma
Metastatic Cervical Carcinoma
Metastatic Colorectal Carcinoma
Metastatic Malignant Solid Neoplasm
Metastatic Melanoma
Metastatic Pancreatic Ductal Adenocarcinoma
Metastatic Renal Cell Carcinoma
Stage II Pancreatic Cancer AJCC v8
Stage III Cervical Cancer AJCC v8
Stage III Colorectal Cancer AJCC v8
Stage III Pancreatic Cancer AJCC v8
Stage III Renal Cell Cancer AJCC v8
Stage IV Cervical Cancer AJCC v8
Stage IV Colorectal Cancer AJCC v8
Stage IV Pancreatic Cancer AJCC v8
Stage IV Renal Cell Cancer AJCC v8
Unresectable Cervical Carcinoma
Unresectable Colorectal Carcinoma
Unresectable Malignant Solid Neoplasm
Unresectable Melanoma
Unresectable Pancreatic Ductal Adenocarcinoma
Unresectable Renal Cell Carcinoma

BIOLOGICAL: Aldesleukin
PROCEDURE: Biopsy
PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
DRUG: Cyclophosphamide
PROCEDURE: Excisional Biopsy
DRUG: Fludarabine
PROCEDURE: Magnetic Resonance Imaging
PROCEDURE: Standard Treatment
BIOLOGICAL: Therapeutic Tumor Infiltrating Lymphocytes

24231
NCI-2024-08121 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
24231 (OTHER Identifier) (OTHER: City of Hope Medical Center)
P30CA033572 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-10-02	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-22
First Submitted that Met QC Criteria 2024-10-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2025-08-26
First Posted (ESTIMATED) 2024-10-03	Results First Posted N/A	Last Verified 2025-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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,	BIOLOGICAL: Aldesleukin Given SC PROCEDURE: Biopsy Undergo biopsy PROCEDURE: Biospecimen Collection Undergo blood sample collection PROCEDURE: Computed Tomography Undergo CT DRUG: Cyclophosphamide Given IV PROCEDURE: Excisional Biopsy Undergo excisional biopsy DRUG: Fludarabine Given IV PROCEDURE: Magnetic Resonance Imaging Undergo MRI PROCEDURE: Standard Treatment Receive standard of care therapy BIOLOGICAL: Therapeutic Tumor Infiltrating Lymphocytes Given STIL101 for injection IV

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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,

BIOLOGICAL: Aldesleukin

Given SC

PROCEDURE: Biopsy

Undergo biopsy

PROCEDURE: Biospecimen Collection

Undergo blood sample collection

PROCEDURE: Computed Tomography

Undergo CT

DRUG: Cyclophosphamide

Given IV

PROCEDURE: Excisional Biopsy

Undergo excisional biopsy

DRUG: Fludarabine

Given IV

PROCEDURE: Magnetic Resonance Imaging

Undergo MRI

PROCEDURE: Standard Treatment

Receive standard of care therapy

BIOLOGICAL: Therapeutic Tumor Infiltrating Lymphocytes

Given STIL101 for injection IV

Primary Outcome Measures	Measure Description	Time Frame
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.	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.	Up to 2 years

Secondary Outcome Measures	Measure Description	Time Frame
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.	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.	From start of STIL101 for injection infusion for at least one post-treatment scan up to 2 years
Overall survival	Analysis will be descriptive.	From the start of STIL101 for injection until death due to any cause up to 2 years
Overall survival	Analysis will be descriptive.	From excisional biopsy until death due to any cause up to 2 years
Progression-free survival	Analysis will be descriptive.	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.	Up to 2 years
Time to lymphodepleting chemotherapy	Analysis will be descriptive.	From subject informed consent to start of lymphodepleting chemotherapy up to 2 years
Excisional biopsy complication rate	Analysis will be descriptive.	Up to 2 years
STIL101 for injection generation times	Analysis will be descriptive.	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.	Up to 2 years
STIL101 cell count	STIL101 cell count in patients with respect to baseline characteristics, clinical outcome and AEs will be described.	Up to 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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)

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Vincent Chung, City of Hope Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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