A phase 2, Multicenter Study of TILs Treatment in Advanced Tumors with Alterations in the SWI/SNF Complex: the TILTS Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut D Investigacio Biomedica De Bellvitge IDIBELL

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Aug 2024 → ongoing

Decision date (initial)

2023-09-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Instituto de Salud Carlos III

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Others

To evaluate the efficacy of autologous TIL (VHIO-TIL-01) as a single therapy in patients affected by unresectable or advanced tumors with alterations in the SWI-SNF complex, as determined by ORR, using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as assessed by Investigator

Secondary objectives 5

1. Benefit in terms of survival as determined by progression-free survival (PFS) and overall survival (OS).
2. To determine exploratory response/activity endpoints (CRR, DOR, and DCR)
3. To characterize the safety profile of TIL (VHIO-TIL-01) as a single therapy in the abovementioned patients, as measured by the incidence of Grade ≥3 treatment-emergent adverse events (TEAEs).
4. To study mechanisms of immunogenicity, antigen recognition, TILs anti-tumor activity in tumors with initiating alterations in the SWI/SNF complex, and changes in the stool microbiome and specific TCR population during treatment.
5. To analyze tumor immune microenvironment in samples of tumors associated with alterations in the SWI/SNF complex as a tumor initiating event, or common cancers with acquired SWI/SNF complex mutations

Conditions and MedDRA coding

Advanced solid tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 3.All patients must have a pathologically confirmed diagnosis of solid tumors associated with SWI/SNFc-mutated monogenic diseases. These solid tumors include, but are not limited to: - Epithelioid sarcoma - Malignant rhabdoid tumor - Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) - Renal medullary carcinoma - Epithelioid malignant peripheral nerve sheath tumor (EMPNST) - Myoepithelial carcinoma - Extra-skeletal myxoid chondrosarcoma - Poorly differentiated chordoma - Sinonasal basaloid carcinoma
2. 4. Patients must have a measurable disease as defined by RECIST 1.1: - Lesions in previously irradiated areas should not be selected as target lesions unless there has been demonstrated progression in those lesions. - Lesions that are partially resected for TIL generation that are still measurable per RECIST may be selected as target lesions
3. 11. Patients must have a washout period from prior anticancer therapy(ies) of a minimum duration, as detailed below prior to the first study treatment (ie, start of NMA-LD). - Chemotherapy: adjuvant, neoadjuvant or definitive chemotherapy/ chemoradiation is allowed provided the washout is a minimum of 21 days, prior to the start of treatment. - Prior immunotherapy, checkpoint-targeted therapy, other monoclonal antibodies (mAbs), or vaccines are allowed if disease progression is confirmed prior to or within the washout period of ≥21 days prior to the start of NMA-LD
4. 12. Palliative radiation therapy: prior external beam radiation is allowed at least 2 weeks before TILs infusion provided all radiation-related toxicities are resolved to Grade 1 or baseline, excluding alopecia, skin pigmentation change, or other clinically insignificant events, eg, small area radiation dermatitis or rectal or urinary urgency.

Exclusion criteria 8

1. 1. Patients who have received an organ allograft or prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen within the past 20 years
2. 2. Patients with symptomatic and/or untreated brain metastases: - Patients with definitively-treated brain metastases will be considered for enrollment if, prior to the start of treatment the patient is clinically stable for ≥ 2 weeks, there are no new brain lesions via magnetic resonance imaging (MRI) post-treatment, and the patient does not require ongoing corticosteroid treatment.
3. 3. Patients requiring regular treatment with steroids at a dose higher than prednisone 10mg/day (or equivalent)
4. 6. Patients may not have active or prior documented autoimmune or inflammatory disorders (including pneumonitis, inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).
5. 9. Patients with a history of hypersensitivity to any of the folowing drugs including, but not limited to, the components of the study drugs and any component of TIL product formulation: - NMA-LD (cyclophosphamide, mesna, and fludarabine) - Proleukin®, aldesleukin, IL-2 - Antibiotics of the aminoglycoside group (ie, streptomycin, gentamicin [excluding those who are skin-test negative for gentamicin hypersensitivity]) - Any component of the TIL product formulation including dimethyl sulfoxide [DMSO], human serum albumin [HSA], IL-2, and dextran-40
6. 10. Patients who have a left ventricular ejection fraction (LVEF) <45% or who are New York Heart Association (NYHA) Class II or higher
7. 11. Patients who have obstructive or restrictive pulmonary disease and have a documented FEV1 (forced expiratory volume in 1 second) ≤50% of predicted normal
8. 12. Patients who have had another primary malignancy within the previous 3 years (except for those which do not require treatment or have been curatively treated >1 year ago, and in the judgment of the Investigator, does not pose a significant risk of recurrence including, but not limited to, non-melanoma skin cancer, DCIS, LCIS, prostate cancer Gleason score ≤6 or bladder cancer).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • ORR per RECIST v1.1 as assessed by investigator

Secondary endpoints 6

1. • Toxicity evaluation: nature and frequency of Adverse Events (AE), Severe Adverse Events (SAE), Treatment-limiting Toxicity (TLT), alterations in clinical, laboratory test results, ECGs, vital sign measurements, physical examination findings graded, when applicable, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
2. • CRR per RECIST v1.1 as assessed by investigator
3. • DOR per RECIST v1.1 as assessed by investigator
4. • DCR per RECIST v1.1 as assessed by investigator
5. • PFS per RECIST v1.1 as assessed by investigator
6. OS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut D Investigacio Biomedica De Bellvitge IDIBELL

Sponsor organisation

Fundacio Institut D Investigacio Biomedica De Bellvitge IDIBELL

Address

Avinguda De La Gran Via De L'hospitalet 199

City

L'hospitalet De Llobregat

Postcode

08908

Country

Spain

Scientific contact point

Organisation

Fundacio Institut D Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Juan Martín Liberal

Public contact point

Organisation

Fundacio Institut D Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Juan Martín Liberal

Third parties 4

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications