Refractory Advanced diGestive Neuroendocrine Carcinomas Treated With tARlatamab

NCT07061080 | Recruiting Phase 2 DMC

• 2 other identifiers: GETNE T24192024-514327-42-00
• Study Type: interventional
• Target: 87
• Locations: 2 countries
• Sites: 19

Brief Summary

Neuroendocrine neoplasms (NENs) comprise a heterogeneous family of neoplasms arising from the neuroendocrine cells localized in endocrine glands or from the diffuse neuroendocrine cells such as in the digestive or lung tract. Treatment for gastroenteropancreatic neuroendocrine tumors (GEP-NEC) is primarily based on chemotherapy regimens, primarily platinum, which achieve limited benefit and a median overall survival of approximately 12 months. Currently, new treatments that activate the immune system to stimulate antitumor responses and prolong survival in patients with NECs are being investigated. Given the high levels of DLL3 expression on the cell surface of neuroendocrine tumor cells and its minimal, primarily cytoplasmic, localization in normal tissues, DLL3 is a promising target for the development of T-cell-directed therapies in NECs. Tarlatamab is a HLE BiTE molecule that combines the binding specificities for DLL3 and CD3, which could activate the immune system to fight NEC cells. The main hypothesis is that treatment with tarlatamab, a bispecific anti-DLL3 and anti-CD3 conjugate, either as a single agent or in combination with standard second-line chemotherapy (FOLFIRI) scheme could be an effective treatment option for patients with advanced neuroendocrine carcinomas of the digestive system or unknown primary origin.

Conditions

Advanced Neuroendocrine Carcinomas of The Digestive System; Advanced Neuroendocrine Carcinomas Unknown Primary Origin

Keywords

Digestive Neuroendocrine carcinomas; Tarlatamab; FOLFIRI; NECs; GEP-NEN

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) rate

  The percentage of patients without progression as defined by RECIST V1.1 criteria or death. PFS rate will be calculated for each treatment arm separately once 38 PFS events are reported in the first 54 patients included (27 per treatment arm). Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment.

  Throughout the study period, with an average follow-up of 3 years

• Overall Survival (OS) rate at 12-months

  Defined as the percentage of patients alive after 12 months from the first dose of study treatment. OS will consider death from any cause as an event. Patients alive and free of events at the date of the analysis will be censored at their last known contact. OS will be calculated for each treatment arm separately. We will assess the median OS, estimated by Kaplan-Meier. Patients alive and free of events at the date of the analysis will be censored at their last known contact. Survival will be assessed by recording patient status at each visit according to protocol. Long term follow up to be performed at least every 6 months

  Throughout the study period, at 12 months from the start of treatment

Secondary Outcomes (5)

• Objective response rate (ORR)

  Throughout the study period, with an average follow-up of 3 years

• Disease control rate (DCR)

  Throughout the study period, with an average follow-up of 3 years

• Duration of response (DoR)

  Throughout the study period, with an average follow-up of 3 years

• Patient reported health-related quality of life (HRQoL)

  Throughout the study period, with an average follow-up of 3 years

• Frequency and severity of adverse events and Treatment-related adverse events (TRAEs)

  Throughout the study period, with an average follow-up of 3 years

Study Arms (2)

Arm A: Tarlatamab

ACTIVE COMPARATOR

Tarlatamab as a standalone treatment through intravenous infusion at 10 mg dose every 14 days (i.e. 2 weeks).

Drug: Tarlatamab

ARM B: Tarlatamab plus FOLFIRI

EXPERIMENTAL

Tarlatamab as intravenous infusion at 10mg in combination with the standard of care second-line chemotherapy (FOLFIRI)

Drug: Tarlatamab; Drug: standard of care second-line chemotherapy (FOLFIRI)

Interventions

standard of care second-line chemotherapy (FOLFIRI) DRUG

FOLFIRI:: irinotecan intravenously 180 mg/m2 on day 1, followed by 400 mg/m2 folinic acid or 200 mg/m² levofolinate in a 2-h infusion, a 10-min bolus of 400 mg/m2 5-FU, and 2400 mg/m2 5-FU over 46 hours; every 14 days).

ARM B: Tarlatamab plus FOLFIRI

Tarlatamab DRUG

Tarlatamab as a standalone treatment through intravenous infusion at 10 mg dose every 14 days (i.e. 2 weeks)

ARM B: Tarlatamab plus FOLFIRI; Arm A: Tarlatamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent.
• Patient is ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Histologically confirmed neuroendocrine carcinomas (NECs) of the digestive system or unknown primary origin.
• Note: Carcinomas of pulmonary origin are not eligible.
• Ki-67 \>20% or mitotic rate \> 20 per 10 HPF.
• Metastatic or locally advanced unresectable disease in the second-line treatment, after progression to either:
• first-line therapy with platinum-based chemotherapy,
• first-line combination of immunotherapy chemotherapy (excluding BITE CD3/DLL3).
• At least one measurable lesion as defined by RECIST V1.1 (Appendix 3).
• Only patients with tumors positive for DLL3 as determined by the central laboratory are eligible. DLL3 positivity is defined as ≥1% of DLL3-expressing cells.
• Note: An archival tumor tissue sample (frozen tumor block or 15 unstained formalin fixed, paraffin embedded \[FFPE\] slides) should be available for submission to the central laboratory for the determination of DLL3. Patients will sign a screening ICF and tumor samples will be sent to the central laboratory for assessing DLL3. Patients who do not have archived tumor tissue available should undergo tumor biopsy.
• Adequate organ function as defined below
• Neutrophil count (ANC) ≥ 1.5 × 109/L.
• Platelet count ≥ 100 × 109/L.

You may not qualify if:

• The following endocrine tumor types may not be included:
• Paraganglioma, adrenal, thyroid parathyroid or pituitary endocrine tumors,
• Large or small cell lung neuroendocrine carcinoma of the lung,
• Neuroendocrine tumors (NETs) of the gastrointestinal tract or unknown origin (i.e. well differentiated tumors)
• History of other malignancy within the past 2 years prior to first dose of tarlatamab except:
• Malignancy (other than in situ) treated with curative intent and with no known active disease present for 2 years before first dose of tarlatamab and felt to be at low risk for recurrence by the treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated in situ cancer without evidence of disease.
• Prostatic intraepithelial neoplasia without evidence of prostate cancer.
• Adequately treated urothelial papillary non-invasive carcinoma.
• Prior anti-cancer therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and first dose of tarlatamab.
• Persistence of any toxicity from prior anti-tumor therapy that has not been resolved to grade ≤ 1 (NCI CTCAE V5.0) or to levels dictated in the eligibility criteria.
• Major surgery within 28 days of first dose tarlatamab.
• Radiation therapy \< 2 weeks prior to starting study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
• Myocardial infarction, and/or symptomatic congestive heart failure (New York Heart Association class II) within 12 months of first dose of tarlatamab.

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead
• Amgen: collaborator

Study Sites (19)

Brest University Hospital Centre

Brest, Brest, 29200, France

NOT YET RECRUITING

Centre Régional de Lutte Contre le Cancer Institut Bergonié (Bordeaux)

Bordeaux, Cedex, 33076, France

NOT YET RECRUITING

Centre Oscar Lambret

Lille, Lille, 59020, France

NOT YET RECRUITING

Hôpital Edouard Herriot (Hospices Civils Lyon)

Lyon, Lyon, 69003, France

NOT YET RECRUITING

Institut de Cancérologie de l'Ouest (Angers/Nantes)

Nantes, Nantes, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Toulouse

Toulouse, Toulouse, 31300, France

NOT YET RECRUITING

Institut de Cancérologie de Lorraine (CLCC) Nancy

Vandœuvre-lès-Nancy, Vandœuvre-lès-Nancy Cedex, 54519, France

NOT YET RECRUITING

Gustave Roussy

Villejuif, Villejuif,, 94800, France

NOT YET RECRUITING

Hospital Clínico Universitario de Santiago

Santiago de Compostela, A Coruña, 15706, Spain

NOT YET RECRUITING

H.U Germans Trias i Pujols

Badalona, Barcelona, 08916, Spain

NOT YET RECRUITING

H.U. Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Universitario de Burgos (HUBU)

Burgos, Burgos, 09006, Spain

NOT YET RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

NOT YET RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

NOT YET RECRUITING

H.U Ramón y Cajal

Madrid, Madrid, 28034, Spain

NOT YET RECRUITING

Hospital 12 de Octubre

Madrid, Madrid, 28041, Spain

NOT YET RECRUITING

H.U La Paz

Madrid, Madrid, 28046, Spain

NOT YET RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46026, Spain

NOT YET RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, Zaragoza, 50009, Spain

NOT YET RECRUITING

Study Officials

• Jaume Capdevila, M.D., Ph.D.

  Hospital Vall d'hebrón

  STUDY CHAIR

Central Study Contacts

Federico Nepote, M.D., PhD.

CONTACT

+34 93 434 44 12; investigacion@mfar.net

Jaume Capdevila, M.D., Ph.D.

CONTACT

+34 93 434 44 12; investigacion@mfar.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized 1:1 to receive: arm A) Tarlatamab or Arm B) Tarlatamab plus FOLFIRI. After the observation of 38 PFS events, an interim analysis will be performed to identify the treatment arm with better PFS and safety outcomes. The decision on which arm should be continued for the second part of the trial will be done taking into account both, PFS and safety profile. The decision will be taken by a scientific committee composed of 4 oncologists. At the time of the interim analysis is expected to have included approximately 54 patients (27 per treatment arm). In the second part of the trial, the study will continue recruitment treating all patients with the selected treatment according to the scientific committee . The study will be open until the recruitment of 60 patients in this treatment arm (27 + 33).

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: July 11, 2025
• Study Start: December 18, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (11); FR (8)