Multicenter, open label, single arm, phase II study to assess the efficay and safety of enfortumab-vedotin (EV) as a single agent in patients with advanced Neuroendocrine Carcinomas (NEC).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Grupo Espanol De Tumores Neuroendocrinos

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

13 Mar 2025 → ongoing

Decision date (initial)

2025-02-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Grupo GETNE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess efficacy in terms of the objective radiological response rate of single-agent EV in patients with locally advanced or metastatic NEC, of any origin except lung, or NET-G3 with a Ki-67 index > 20% of any origin, excluding lung that are refractory to or ineligible for first-line platinum-based chemotherapy.

Secondary objectives 5

1. To evaluate the duration of response (DOR).
2. To evaluate progression-free survival (PFS) with the study treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for subjects treated with EV.
3. To evaluate overall survival (OS).
4. To evaluate the safety and tolerability of EV.
5. Exploratoy Objective: Translational correlation between the tissue expression of nectin-4 and the clinical outcomes.

Conditions and MedDRA coding

Neuroendocrine Carcinoma / G3 Neuroendocrine Tumours

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patients 18 years of age or older.
2. Patients who give informed consent to participate in the study.
3. Patients with histologically documented poorly-differentiated neuroendocrine carcinoma of any origin, excluding the lung, or histologically documented well-differentiated neuroendocrine tumours of grade 3 histology with a Ki-67 index >20%, of any origin, excluding the lung, who have failed at least one prior line of platinum-based systemic therapy or are considered ineligible for platinum-based chemotherapy
4. Patients with radiologically documented metastatic or locally advanced disease at the start of the study. Subjects with brain metastases must have clinically controlled neurological symptoms and must have completed radiotherapy at least 21 days prior to administration of the first dose of study drug.
5. Patients with ECOG score 0-2.
6. Evaluable and/or measurable disease by CT scan according to RECIST v1.1.
7. Patients must have adequate renal and hepatic function according to the local laboratory reference ranges at the time of screening: - Absolute neutrophil count ≥ 1500/µcL - Platelets ≥ 80,000/mm3 - Haemoglobin ≥ 9.0 g/dL - Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 30 mL/min - Sodium > 130 mmol/L - Alkaline phosphatase, AST and ALT ≤ 2.5 x ULN - Bilirubin ≤ 1.5 x ULN - Patients with liver metastases may have ALP, AST and ALT ≤ 5.0 x ULN - Patients with bone metastases may have alkaline phosphatase ≤ 5.0 x ULN - Patients with Gilbert’s syndrome may have bilirubin > 1.5 x ULN - Coagulation: activated partial thromboplastin time (aPTT), prothrombin time (PT) ≤ 1.2 x ULN.
8. Life expectancy of at least 12 weeks.
9. Women must be surgically sterile, post-menopausal (for at least 1 year), or have a negative pregnancy test.
10. Women who are not surgically sterile or post-menopausal (for at least one year) and men who have not had a vasectomy must use highly effective contraception measures. (Please see section 13.3.8 of protocol for further details).

Exclusion criteria 11

1. Prior systemic treatment with any antimicrotubule agent such as taxanes or Enfortumab Vedotin, or more than two lines of chemotherapy-based systemic therapy, excluding adjuvant or neoadjuvant treatments.
2. Grade 2 or higher peripheral neuropathy.
3. Patients with evidence of other severe uncontrolled disease as judged by the investigator.
4. Patients with active immune thrombocytopenic purpura, autoimmune haemolytic anaemia, or a history of being refractory to platelet transfusions (within 1 year prior to the 1st dose of study drug).
5. Patients with a significant history of uncontrolled cardiovascular disease or renal, neurological, psychiatric, endocrine, metabolic, immunological, or hepatic disease.
6. Women who are pregnant or breastfeeding.
7. Patients with a history of other active malignancies within three years prior to study start, with the exception of: adequately treated carcinoma in situ of the cervix, basal or squamous cell carcinoma of the skin, or prior confined malignancy surgically resected with curative intent.
8. Patients having received any anticancer therapy within 14 days prior to the first dose of study drug.
9. Patients undergoing major surgery in the four weeks prior to the first dose of study drug.
10. Patients with known hypersensitivity to EV or any excipient contained in the EV pharmaceutical formulation (including histidine, trehalose dihydrate, and polysorbate 20).
11. Patients with poorly controlled diabetes (glycated haemoglobin ≥ 10%).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR) according to RECIST v1.1.

Secondary endpoints 5

1. Progression-free survival (PFS): The time from the start of the first dose of the study treatment to the first objective documentation of tumour progression or death from any cause.
2. Duration of response (DOR): The time from the first documentation of confirmed objective response (CR or PR) to the first objective documentation of tumour progression or death due to any reason.
3. Overall survival (OS): The time from the start of the first dose of the study treatment to death due to any reason.
4. Absolute and relative frequencies of patients experiencing adverse events (AEs), patients experiencing serious adverse events (SAEs), patients experiencing adverse reactions (ARs), patients experiencing serious adverse reactions (SARs) and patients experiencing suspected unexpected serious adverse reactions (SUSARs). Absolute frequencies of recorded AEs, recorded SAEs, recorded ARs, recorded SARs and recorded SUSARs.
5. Exploratory variables: Expression levels of nectin-4 determined by immunohistochemistry in the tumour block of the diagnostic biopsy.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Grupo Espanol De Tumores Neuroendocrinos

Sponsor organisation

Grupo Espanol De Tumores Neuroendocrinos

Address

Calle Paris 162 Principal 1ª

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

Grupo Espanol De Tumores Neuroendocrinos

Contact name

Medical Oncology

Public contact point

Organisation

Grupo Espanol De Tumores Neuroendocrinos

Contact name

Medical Oncology

Third parties 1

Locations

1 EU/EEA country · 10 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 6 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