Assessment of the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors
- Conditions
- Epithelial Tumors, MalignantMalignant Solid Tumor
- Interventions
- Registration Number
- NCT05141474
- Lead Sponsor
- Vall d'Hebron Institute of Oncology
- Brief Summary
Background:
The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity.
Adoptive cell therapy using tumor-infiltrating lymphocytes product (TIL-ACT) is a well-established combination therapy currently under study in several world reference centers, using an autologous cell product without genetic modifications. This cell product consists of tumor-infiltrating lymphocytes (TIL), which are collected from the patient and expanded in the lab under specific conditions to enhance its antitumoral efficacy before reinfusion in the same patient. However, this cell product alone does not achieve adequate efficacy, and a combination of both previous non-myeloablative lymphodepleting (NMA-LD) chemotherapy and subsequent cytokine therapy (specifically IL-2) is needed to support the expansion of the infused cells.
The investigators hypothesize that TILs enriched for neoantigen recognition are superior to unselected TILs at mediating tumor regression in patients with epithelial tumors and even other solid tumors where immune checkpoint blockade (ICB) is approved and used as part of standard therapy. The investigators propose to manufacture a T-cell product composed of TILs that are selected based on their ability to recognize patient-specific neoantigens and to use these to treat patients with metastatic, refractory, epithelial cancers, as well as ICB-resistant solid tumors. Furthermore, it also proposed to study the tumor and T cells at baseline and after treatment to investigate whether specific phenotypic and functional traits may be associated with clinical outcome.
Primary objective:
To evaluate the safety and the tolerability of ex vivo next generation neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) in patients with metastatic or unresectable epithelial tumors and immune checkpoint blockade (ICB) resistant solid tumors.
Secondary objectives:
* To determine the success in producing active specific TILs from our target patients.
* To evaluate the initial clinical activity of the NEXTGEN-TIL products in our target patients.
- Detailed Description
Methods:
This study is a first-in-human, open-label, non-controlled, single-centre, phase I trial to assess the safety and tolerability of NEXTGEN-TIL-ACT. Given the exploratory nature of the study, there is no formal hypothesis testing and no formal sample size calculation was carried out.
A sample size of 10 patients has been selected to provide information about the frequency of treatment-limiting toxicity (TLT).
Study treatment:
The main study therapy is the Tumor-infiltrating Lymphocyte (NEXTGEN-TIL) product, which is preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion.
NEXTGEN-TIL product is a cellular investigational product comprising a live cell suspension of autologous tumor-infiltrating lymphocytes derived from the patient's own tumor.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description NEXTGEN-TIL Non-myeloablative Lymphodepletion (NMA-LD) Regimen Subjects will receive a therapy based on Tumor-infiltrating Lymphocyte (NEXTGEN-TIL product) preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion. Patients will be followed-up for 2 years, assessed at weeks 2, 3, 4, 6, 9, 12, 18, 24, 30, 36 (9 months), and then at 1 year, 1,5 and 2 years. NEXTGEN-TIL Interleukin-2 Subjects will receive a therapy based on Tumor-infiltrating Lymphocyte (NEXTGEN-TIL product) preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion. Patients will be followed-up for 2 years, assessed at weeks 2, 3, 4, 6, 9, 12, 18, 24, 30, 36 (9 months), and then at 1 year, 1,5 and 2 years. NEXTGEN-TIL NEXTGEN-TIL Subjects will receive a therapy based on Tumor-infiltrating Lymphocyte (NEXTGEN-TIL product) preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion. Patients will be followed-up for 2 years, assessed at weeks 2, 3, 4, 6, 9, 12, 18, 24, 30, 36 (9 months), and then at 1 year, 1,5 and 2 years.
- Primary Outcome Measures
Name Time Method Incidence of Serious Adverse Events (SAE) From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first Nature and frequency of SAE, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Incidence of alterations in clinical laboratory test results From baseline through study completion, an average of 2 years Nature and frequency of abnormalities found in clinical laboratory test results
Incidence of physical examination findings From baseline through study completion, an average of 2 years Nature and frequency of abnormalities found in the physical examination.
Assessment of performance status From baseline through study completion, an average of 2 years Patient performance status assessed as per Eastern Cooperative Oncology Group (ECOG) score, where grade 0 is for fully active and capable patient and grade 5 is death.
Incidence of Adverse Events (AE) From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first Nature and frequency of AE, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Treatment-limiting Toxicity (TLT) From the first dose of study treatment (Day -5) to 30 days after Toxicities related to treatment administration that, if recurrent at high enough frequency (≥2 patients treated), should trigger review by the Independent Data Safety Monitoring Board (IDSMB), which could lead to recommendations for treatment modifications for subsequent patients.
Incidence of alterations in electrocardiogram assessment From baseline through study completion, an average of 2 years Nature and frequency of abnormalities found in electrocardiogram
Incidence of alterations in vital signs measurements From baseline through study completion, an average of 2 years Nature and frequency of abnormalities found in vital signs.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) From baseline through disease progression, assessed up to 36 months after last dose of IL-2 DOR per RECIST v1.1 as assessed by investigator, defined as the time elapsed between the initial response to therapy and subsequent disease progression or relapse.
Progression-Free Survival (PFS) From baseline through disease progression, assessed up to 36 months after last dose of IL-2 PFS per RECIST v1.1 as assessed by investigator, defined as the time from the date of treatment administration to the date of first documentation of disease progression or death due to any cause, whichever occurs first. For a patient who has not progressed and is last known to be alive, PFS will be censored at the last response assessment that is stable disease (SD) or better.
Neoantigen-selected TIL analysis At baseline Rate of successful neoantigen-selected TIL (NEXTGEN-TIL) generation from biopsied patients and frequency of neoantigen-specific TILs in all TILs produced from biopsied patients included in this trial.
Overall Response Rate (ORR) From baseline through disease progression, assessed up to 36 months after last dose of IL-2 ORR per RECIST v1.1 as assessed by investigator, defined as proportion of patients who have a partial or complete response to therapy.
Trial Locations
- Locations (1)
Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain