NeoTIL in Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT04643574|
Recruitment Status : Not yet recruiting
First Posted : November 25, 2020
Last Update Posted : November 25, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor, Adult||Other: NeoTIL Drug: Cyclophosphamide Drug: Fludarabine Drug: Interleukin-2 Other: Radiotherapy||Phase 1|
The objective of the trial is to define the feasibility, safety, and efficacy of NeoTIL-ACT in combination with LDI in patients with advanced, recurrent or metastatic solid tumors, as categorized in two molecularly defined cohorts.
Study treatment will begin with intravenous (IV) non-myeloablative (NMA) lymphodepleting chemotherapy composed by fludarabine and cyclophosphamide. Both treatments will be started on the same day. Fludarabine will be administered from for five days, and cyclophosphamide ffor two days. Low-dose irradiation (LDI) will be administered once, to tumor lesions using tomotherapy.
Patients will receive NeoTIL infusion intravenously followed by high dose IL-2 administration every eight hours, for a maximum of eight doses. Supportive care will be given as needed during the whole treatment period.
Patients achieving a stable disease, partial response or complete response after NeoTIL-ACT treatment will then enter a clinical follow-up period for 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study to Assess the Feasibility, Safety and Efficacy of Adoptive Transfer of Autologous Tumor-Infiltrating Lymphocytes Enriched for Tumor Antigen Specificity (NeoTIL) in Advanced Solid Tumors|
|Estimated Study Start Date :||November 2020|
|Estimated Primary Completion Date :||November 2027|
|Estimated Study Completion Date :||November 2027|
Experimental: NeoTIL-ACT + LDI
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).
Adoptive transfer of ex vivo expanded Autologous Tumor-Infiltrating Lymphocytes enriched for tumor antigen specificity (NeoTIL)
Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.
Fludarabine will be administered as an intravenous (IV) infusion for five days.
After TIL infusion, IL-2 (optional) will be started as a bolus administration every eight hours, for a maximum of eight doses.
Low-dose irradiation (1Gy) will be administered using tomotherapy to tumor lesions once before NeoTIL infusion.
- Evaluation of the number of patients who successfully receive NeoTIL-ACT in combination with LDI (feasibility) [ Time Frame: Evaluated for each patient at day 0 ]
- Planned NMA chemotherapy regimen
- Planned LDI
- At least partial NeoTIL infusion
- No minimum IL-2 requirement
- Toxicity of NeoTIL-ACT in combination with LDI [ Time Frame: Treatment limiting toxicity (TLT) period: from day starting NMA chemotherapy to day 30 post NeoTIL infusion ]Number of patients with adverse events as assessed by CTCAE version 5.0
- Objective response rate (ORR; efficacy of NeoTIL-ACT in combination with LDI) [ Time Frame: Up to 6 months ]Defined as best overall response (complete response or partial response) accross all assessment time points, according to RECIST 1.1, mRECIST for mesothelioma or PCWG3 for prostate cancer
- Disease Control Rate (DCR) [ Time Frame: 1, 3, 6, 9,12 months ]Achievement of complete response, partial response or stable disease
- Objective response rate (ORR) [ Time Frame: 1, 3, 6, 9, 12 months ]Best overall response
- Progression free survival (PFS) [ Time Frame: 5 years ]Time from enrollment until objective tumor progression or death
- Overall survival (OS) [ Time Frame: 5 years ]Time from enrollment until death from any cause
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04643574
|Contact: Lana Kandalaft, Pharm D, PhDemail@example.com|
|CHUV Oncology Department|
|Lausanne, Vaud, Switzerland, 1011|
|Contact: George Coukos, MD, PhD +41213140627 firstname.lastname@example.org|
|Principal Investigator:||George Coukos, MD, PhD||Centre Hospitalier Universitaire Vaudois|