NeoTIL in Advanced Solid Tumors

NCT04643574 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: CHUV-D0-0018-NeoTIL-2019
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Single center, single arm pilot trial to test the feasibility, safety and efficacy of NeoTIL-ACT combined with low-dose irradiation (LDI) in patients with advanced, recurrent or metastatic solid tumors. The trial is based on lymphodepleting chemotherapy followed by LDI, and then ACT utilizing ex vivo expanded TIL, enriched for tumor antigen specificity (NeoTIL), in combination with high dose Interleukin-2 (IL-2) (optional, depending on patient's tolerance). LDI will be administered once to metastatic lesions using tomotherapy.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (3)

• Evaluation of the number of patients who successfully receive NeoTIL-ACT in combination with LDI (feasibility)

  Defined as: * Planned NMA chemotherapy regimen * Planned LDI * At least partial NeoTIL infusion * No minimum IL-2 requirement

  Evaluated for each patient at day 0

• Toxicity of NeoTIL-ACT in combination with LDI

  Number of patients with adverse events as assessed by CTCAE version 5.0

  Treatment limiting toxicity (TLT) period: from day starting NMA chemotherapy to day 30 post NeoTIL infusion

• Objective response rate (ORR; efficacy of NeoTIL-ACT in combination with LDI)

  Defined as best overall response (complete response or partial response) across all assessment time points, according to RECIST 1.1, mRECIST for mesothelioma or PCWG3 for prostate cancer

  Up to 6 months

Secondary Outcomes (4)

• Disease Control Rate (DCR)

  1, 3, 6, 9,12 months

• Objective response rate (ORR)

  1, 3, 6, 9, 12 months

• Progression free survival (PFS)

  5 years

• Overall survival (OS)

  5 years

Study Arms (1)

NeoTIL-ACT + LDI

EXPERIMENTAL

Non-myeloablative lymphodepleting chemotherapy (fludarabine and cyclophosphamide), Low Dose Irradiation (LDI), ex vivo expanded Tumor Infiltrating Lymphocyte (TIL), enriched for tumor antigen specificity (NeoTIL)-Adoptive Cell Therapy (ACT), Interleukin-2 (IL-2).

Biological: NeoTIL; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Radiation: Radiotherapy

Interventions

NeoTIL BIOLOGICAL

Adoptive transfer of ex vivo expanded Autologous Tumor-Infiltrating Lymphocytes enriched for tumor antigen specificity (NeoTIL)

NeoTIL-ACT + LDI

Cyclophosphamide DRUG

Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.

NeoTIL-ACT + LDI

Fludarabine DRUG

Fludarabine will be administered as an intravenous (IV) infusion for five days.

NeoTIL-ACT + LDI

Interleukin-2 DRUG

After TIL infusion, IL-2 (optional) will be started as a bolus administration every eight hours, for a maximum of fourteen doses.

NeoTIL-ACT + LDI

Radiotherapy RADIATION

Low-dose irradiation (1Gy) will be administered using tomotherapy to tumor lesions once before NeoTIL infusion.

NeoTIL-ACT + LDI

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced (not radically treatable), recurrent or metastatic solid tumors of any histology with the exception of primary central nervous system tumors, who have received, and then progressed or been intolerant to at least one standard therapy regimen in the advanced or metastatic setting if such a therapy exists, and have been considered for all other potentially efficacious therapies prior to enrollment. If the participant refuses, or is not eligible for these regimens in the opinion of the investigator, the reason must be documented in the medical record.
• Patients who have previously undergone tumor resection or biopsy and for whom pre-Rapid Expansion Protocol (REP) NeoTIL cultures are ongoing or completed.
• At least one lesion accessible to biopsy for translational research (TR) at baseline and D30, without putting the patient at unusual risk.
• Male or female age ≥ 18 to ≤ 70 years at the time of informed consent. Patients aged \>70 will be evaluated by the investigator, and decision will be made according to patient's status, upon agreement with the PI.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) of 0 to 2.
• Life expectancy of greater than 12 weeks.
• Radiologically measurable disease (as per Response Evaluation Criteria in Solid Tumours \[RECIST\] v1.1).
• Modified RECIST should be used for mesothelioma
• Prostate Cancer Working Group 3 (PCWG3) criteria should be used for prostate cancer
• Adequate serology defined by the following laboratory results:
• Negative test for Human Immunodeficiency Virus (HIV)
• Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at pre-screening) are not eligible.
• Patients with past/resolved Hepatitis B virus (HBV) infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen (anti-HBc) antibody test) are eligible, if HBV deoxyribonucleic acid (DNA) test is negative.
• HBV DNA must be obtained in patients with positive hepatitis B core antibody prior start of study treatment.
• Patients with active hepatitis C are not eligible. Patients positive for Hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).

You may not qualify if:

• Patients with an active second malignancy, except for
• non-melanoma skin cancer that has been apparently cured or successfully resected
• carcinoma in situ as long as they have been adequately treated
• Any malignancy that can be adequately managed expectantly without compromising prognosis, and after PI agreement.
• Patients who have a history of malignancy are not considered to have an active malignancy if they have completed therapy since at least 2 years and are considered by their treating investigator to be at ≤ 30% risk for relapse.
• Patients with symptomatic and/or untreated brain metastases. Patients with definitively-treated brain metastases will be considered for enrollment after agreement with PI, as long as lesions are stable for ≥ 14 days prior to beginning the chemotherapy, there are no new brain lesions, and the patient does not require ongoing corticosteroid treatment.
• Patients with known peritoneal metastases who have a recent history of intermittent bowel obstruction (even partial), unless such obstruction has been resolved. Agreement with the PI is mandatory.
• Patients with leptomeningeal carcinomatosis
• History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin)
• History of recent myocardial infarction or unstable angina, either within six months of enrolment
• Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction
• Active severe systemic infections within four weeks prior to beginning of NMA chemotherapy.
• Patient requiring regular systemic immunosuppressive therapy (for example for organ transplantation, chronic rheumatologic disease); all immunosuppressive medications including but not limited to steroids, mycophenolate mofetil, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha (TNF-alpha) agents must have been discontinued within the last two weeks prior to starting NMA chemotherapy.
• Note: Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is permitted
• Note: The use of physiologic corticosteroid replacement therapy is permitted.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

centre hospitalier universitaire vaudois (CHUV)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

MeSH Terms

Interventions

neotil; Cyclophosphamide; fludarabine; Interleukin-2; Radiotherapy

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Therapeutics

Study Officials

• Blanca Navarro-Rodrigo, MD, PhD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

• George Coukos, MD, PhD

  Centre Hospitalier Universitaire Vaudois

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 25, 2020
• Study Start: March 9, 2021
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: February 14, 2025

Record last verified: 2025-02

Locations

CH (1)