NCT05141474: NEXTGENTIL-ACT

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

Recruiting now EARLY_PHASE1 Last updated 7 November 2024

What this trial tests

EARLY_PHASE1 trial testing NEXTGEN-TIL in Epithelial Tumors, Malignant in 10 participants. Currently enrolling.

Timeline

28 October 2021

Primary endpoint
1 January 2027

1 January 2027

Quick facts

Lead sponsor	Vall d'Hebron Institute of Oncology
Phase	EARLY_PHASE1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	28 October 2021
Primary completion	1 January 2027
Estimated completion	1 January 2027
Sites	1 location across Spain

Drugs / interventions tested

• NEXTGEN-TIL — full drug profile →
• Non-myeloablative Lymphodepletion (NMA-LD) Regimen — full drug profile →
• Interleukin-2

Conditions studied

• Epithelial Tumors, Malignant — all drugs for Epithelial Tumors, Malignant →
• Malignant Solid Tumor — all drugs for Malignant Solid Tumor →

Sponsor

Vall d'Hebron Institute of Oncology

Who can join

18 and older, any sex, with Epithelial Tumors, Malignant or Malignant Solid Tumor. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Neoantigens: promising targets for cancer therapy.
   Xie N, Shen G, Gao W, Huang Z, et al · · 2023 · cited 713× · PMID 36604431 · DOI 10.1038/s41392-022-01270-x
2. Current advances and challenges in CAR T-Cell therapy for solid tumors: tumor-associated antigens and the tumor microenvironment.
   Yan T, Zhu L, Chen J. · · 2023 · cited 132× · PMID 36707873 · DOI 10.1186/s40164-023-00373-7
3. Tumor-infiltrating lymphocytes for treatment of solid tumors: It takes two to tango?
   Kazemi MH, Sadri M, Najafi A, Rahimi A, et al · · 2022 · cited 113× · PMID 36389779 · DOI 10.3389/fimmu.2022.1018962
4. Recent clinical researches and technological development in TIL therapy.
   Matsueda S, Chen L, Li H, Yao H, et al · · 2024 · cited 23× · PMID 39264449 · DOI 10.1007/s00262-024-03793-4
5. Tumor neoantigens: Novel strategies for application of cancer immunotherapy.
   Guan H, Wu Y, Li LU, Yang Y, et al · · 2023 · cited 19× · PMID 37415744 · DOI 10.32604/or.2023.029924
6. Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances.
   Wang X, Yuan Z, Li Z, He X, et al · · 2024 · cited 12× · PMID 38426090 · DOI 10.3389/fimmu.2024.1354313
7. New insights into the stemness of adoptively transferred T cells by γc family cytokines.
   Luo M, Gong W, Zhang Y, Li H, et al · · 2023 · cited 12× · PMID 38049832 · DOI 10.1186/s12964-023-01354-3
8. Tumor-Infiltrating Lymphocytes and Adoptive Cell Therapy: State of the Art in Colorectal, Breast and Lung Cancer.
   Zemanek T, Nova Z, Nicodemou A. · · 2023 · cited 9× · PMID 37888965 · DOI 10.33549/physiolres.935155