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

Phase 1

Not yet recruiting

• Conditions: 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
• Interventions: 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

• Registration Number: NCT06626256
• Lead Sponsor: City of Hope Medical Center

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2024-10-02
• Study First Submitted QC: 2024-10-02
• Study First Posted: 2024-10-03
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-06
• Study Start: 2025-04-30
• Primary Completion: 2027-10-30
• Study Completion: 2027-10-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• 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)

Exclusion Criteria

• 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (STIL101 for injection)	Biopsy	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.
Treatment (STIL101 for injection)	Biospecimen Collection	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.
Treatment (STIL101 for injection)	Computed Tomography	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.
Treatment (STIL101 for injection)	Excisional Biopsy	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.
Treatment (STIL101 for injection)	Magnetic Resonance Imaging	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.
Treatment (STIL101 for injection)	Standard Treatment	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.
Treatment (STIL101 for injection)	Therapeutic Tumor Infiltrating Lymphocytes	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.
Treatment (STIL101 for injection)	Aldesleukin	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.
Treatment (STIL101 for injection)	Cyclophosphamide	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.
Treatment (STIL101 for injection)	Fludarabine	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.

Primary Outcome Measures

Name	Time	Method
Infusion limiting toxicities (ILTs)	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)	Up to 2 years	Assessed by NCI CTCAE v 5.0. AEs will be summarized by severity, grade and attribution.

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	Up to 2 years	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.
Disease control rate	From start of STIL101 for injection infusion for at least one post-treatment scan up to 2 years	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.
Overall survival	From excisional biopsy until death due to any cause up to 2 years	Analysis will be descriptive.
Progression-free survival	From start of STIL101 for injection infusion until documented progressive disease or death due to any cause up to 2 years	Analysis will be descriptive.
Failure to receive STIL101 after excisional biopsy	Up to 2 years	Analysis will be descriptive.
Time to lymphodepleting chemotherapy	From subject informed consent to start of lymphodepleting chemotherapy up to 2 years	Analysis will be descriptive.
Excisional biopsy complication rate	Up to 2 years	Analysis will be descriptive.
STIL101 for injection generation times	Up to 2 years	Analysis will be descriptive.
Successful STIL101 for injection generation and administration	Up to 2 years	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.
STIL101 cell count	Up to 2 years	STIL101 cell count in patients with respect to baseline characteristics, clinical outcome and AEs will be described.

Trial Locations

Locations (1)

City of Hope Medical Center; 🇺🇸 Duarte, California, United States