TARLATAMAB for Poorly differentiated pulmonary neuroendocrine carcinoma | Poorly differentiated gastroenteropancreatic neuroendocrine carcinoma

Inclusion criteria

• {"criterion_text":"- Signed Informed consent: Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing\n- Adequate organ function: creatinine clearance > 50 mL/min, Neutrophils count ≥ 1500/mm3; Platelets > 100 000/mm3 ; Hemoglobin > 9 g/dL; AST and ALT < 3 x ULN (upper limit of normal) with total bilirubin ≤ 2 × ULN except subjects with documented Gilbert’s syndrome or liver metastasis, who must have AST and ALT ≤ 5 x ULN and a baseline total bilirubin ≤ 3.0 mg/dL.\n- Full recovery from all toxicities associated with prior treatment, to acceptable baseline status, or a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo.\n- Availability of tumor material for central review processes and translational research projects.\n- Absence of any unstable systemic disease and any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule.\n- Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 7 months after the final dose of cemiplimab; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. They must also refrain from egg cell donation for 7 months after the final dose of cemiplimab. For standard of care treatments, investigator should refer to the current SmPC for recommendations regarding contraception.\n- Men who are sexually active with women of childbearing potential will be instructed to adhere to contraception for a period of 6 months after the last dose of cemiplimab. For standard of care treatments, investigator should refer to the current SmPC for recommendations regarding contraception.\n- Patient covered by a national health insurance.\n- Age ≥ 18 years.\n- WHO Performance status 0 – 1.\n- Life expectancy > 12 weeks.\n- Histologically proven and centrally confirmed poorly differentiated neuroendocrine carcinoma (NEC): large cells for lung NEC (WHO 2015 classification), and large and small cells for extra-gastroenteropancreatic (assessed on archived tissue, with possible pre-screening during first-line).\n- Expression of DLL3 in at least 1% of tumor cells (assessed on archived tissue, with possible pre-screening during first-line)\n- Tumor progression following one platinum based line of therapy.\n- Unresectable locally advanced or metastatic stage.\n- At least one measurable target lesion according to RECIST v1.1 per investigator assessment. The radiological assessment has to be done within the timelines indicated."}

Exclusion criteria

• {"criterion_text":"- Well-differentiated neuroendocrine tumor (NET G1, G2 and G3 according to digestive WHO 2017 classification or typical/atypical carcinoid tumor according to lung WHO 2015 classification)\n- Myocardial infarction and/or symptomatic congestive heart failure (New York Head Association class > class II) within 12 months prior to initiation of study treatment.\n- History of arterial thrombosis (e.g. stroke or transient ischemic attack) within 12 months prior to initiation of study treatment.\n- Symptoms and/or clinical and/or radiological signs suggestive of uncontrolled and/or acute active systemic infection within 7 days prior to first administration ofstudy treatment. Patient with active infection requiring parenteral antibiotic therapy. Upon completion of parental antibiotic therapy and resolution of symptoms, the patient may be considered eligible under the infection criterion.\n- Known sensitivity and/or immediate hypersensitivity to any component of study treatment.\n- History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.\n- Patients with immune pneumonitis, pituitary or thyroid disorders, or pancreatitis under treatment with immuno-oncology agents.\n- Patients reporting infusion-related reactions or severe, life-threatening or recurrent immune-mediated adverse events (grade 2 or higher), including events leading to permanent discontinuation of immuno-oncology agents.\n- Presence of an indwelling line or drain (including the following: percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, peritoneal drain or catheter, pericardial drain or catheter, drain catheter or thoracic drain for pleural fluid collection).\n- Patient with a diagnosis of immunodeficiency or undergoing systemic corticotherapy or any other form of immunosuppressive therapy within 7 days prior to administration of the first dose of study treatment.\n- Known acute or chronic B or C hepatitis by serological evaluation. Patients with serological sequellae of hepatitis (antibodies test serologically positive for virus) without hepatitis could be included.\n- Previous treatment targeting DLL3\n- Patients who are pregnant or breast-feeding, or planning to become pregnant or breast-feed during the trial and within 7 months after the last dose of study treatment.\n- Male not wishing to abstain from sperm donation during the trial and within 6 months of the last study treatment.\n- Vaccination with live or attenuated virus vaccines is not permitted during the 28 days prior to administration of the first dose of treatment, and for the duration of the study. Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be avoided during selection, at least 14 days before the first day of treatment. Live, non-replicating smallpox vaccines (such as Jynneos) against monkeypox infection are permitted during the study (except during cycle 1) in accordance with the center's standard of care and internal recommendations.\n- Active autoimmune disease requiring systemic therapy (except replacement therapy) within the last 2 years or any other disease requiring immunosuppressive therapy during the study.\n- Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study.\n- More than one line of systemic therapy in the metastatic setting. Chemotherapy for non-metastatic stage is not considered as first-line if there is a time interval of at least 6 months between the last dose of chemotherapy for non-metastatic stage and the initiation of first-line chemotherapy for metastatic/recurrent disease.\n- Small cell lung NEC (except as a minor <30% component in mixed tumors)\n- Known EGFR activating mutation or ALK or ROS1 rearrangement for lung NEC\n- Untreated or symptomatic central nervous system (CNS) metastases\n- Leptomeningeal metastasis\n- Patients with a recent history of other malignancies except adequately treated non-melanoma skin cancer, and curatively treated in-situ cancer. Patients with history of solid tumors, including adenocarcinoma, treated in a curative way with or without chemotherapy and without any evidence of disease >2 years before randomisation can be included as well.\n- Major surgery within 28 days prior to initiation of study treatment."}

Primary endpoints

• {"endpoint_text":"- Overall survival (OS) in patients who received at least one dose of treatment.","definition_or_measurement_approach":"Measured by Overall Survival (OS) in patients who received at least one dose of treatment."}

Secondary endpoints

• {"endpoint_text":"- Incidence, nature, and severity of treatment-related adverse events/treatment-emergent adverse events, graded according to the NCI CTCAE v5.0 except CRS and ICANS events graded using ASTCT 2019","definition_or_measurement_approach":"Graded according to NCI CTCAE v5.0; CRS and ICANS graded using ASTCT 2019."}
• {"endpoint_text":"- Objective Response Rate (ORR)","definition_or_measurement_approach":"Listed as a secondary efficacy endpoint (ORR) as stated in the protocol's secondary objectives."}
• {"endpoint_text":"- Duration of response (DoR)","definition_or_measurement_approach":"Listed as a secondary efficacy endpoint (DoR) as stated in the protocol's secondary objectives."}
• {"endpoint_text":"- Disease Control Rate (DCR)","definition_or_measurement_approach":"Listed as a secondary efficacy endpoint (DCR) as stated in the protocol's secondary objectives."}
• {"endpoint_text":"- Progression Free Survival (PFS)","definition_or_measurement_approach":"Listed as a secondary efficacy endpoint (PFS) as stated in the protocol's secondary objectives."}
• {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":"Overall Survival (OS) listed also among secondary endpoints (no additional definition provided)."}
• {"endpoint_text":"- Quality of life of questionnaire EORTC QLQ-C30","definition_or_measurement_approach":"Measured using the EORTC QLQ-C30 questionnaire."}

France

Earliest CTIS Part Ii Submission Date

17-07-2025

Latest Decision Or Authorization Date

02-09-2025

Processing Time Days

47

Number Of Participants

129

Primary sponsor

Full Name

Intergroupe Francophone De Cancerologie Thoracique

Organisation Type

Patient organisation/association

Country Of Registered Address

France