TransBronchial Needle injection of Tremelimumab in early-stage NSCLC patients (TALENT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

Trial duration

3 Nov 2025 → ongoing

Decision date (initial)

2024-10-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Cancer Center Amsterdam (CCA)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Others

To study the safety and feasibility of intra-nodal and intra-tumoral bronchoscopic transbronchial needle injection (TBNI) of tremelimumab in early-stage NSCLC patients.

Secondary objectives 1

1. To assess the pharmacokinetics of endobronchially administered tremelimumab in early-stage lung cancer.

Conditions and MedDRA coding

Non small cell lung cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Pathologically confirmed, T1-2N0M0 NSCLC scheduled for surgical lung tumor resection
2. Willing and able to provide written informed consent for the trial
3. Above 18 years of age on day of signing informed consent
4. Considered a surgical lung tumor resection candidate, as determined by the pulmonologist and lung surgeons at the multidisciplinary tumor meeting.

Exclusion criteria 12

1. Patients deemed inoperable
2. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 0. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
3. Additional malignancy that is progressing or requires active systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., 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.]). The following are exceptions to this criterion: a. Patients with vitiligo or alopecia b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement c. Any chronic skin condition that does not require systemic therapy d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician e. Patients with celiac disease controlled by diet alone
5. Uncontrolled intercurrent illness, including but not limited to symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
6. Active infection requiring systemic therapy.
7. A history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
8. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
9. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
10. Has received prior therapy with an anti-PD-1, anti-PD-L1 including durvalumab, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways in the past year.
11. Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the bronchoscopy.
12. Patients with known oncogenic drivers such as activating EGFR or BRAF mutations or ALK or ROS1 gene rearrangements

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety defined as the proportion of patients with (severe) adverse events up to the date of the scheduled surgical lung tumor resection after intra-nodal and intra-tumoral bronchoscopic administration of tremelimumab. This includes both TBNI procedure related (S)AEs and immune-related (S)AEs.
2. Feasibility defined as successful injection of tremelimumab or saline in the tumor draining lymph node or tumor.

Secondary endpoints 1

1. Pharmacokinetics assessment: levels of therapeutic antibodies in plasma at multiple time points (baseline, 2 hours post TBNI procedure, 1 day post TBNI, 14 (+/- 5 days) days post TBNI and 12 weeks (+/- 7 days) after surgical lung tumor resection ).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Jouke Annema

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Jouke Annema

Locations

1 EU/EEA country · 1 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 7 files

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

Application history

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