A GCO Trial Exploring the Efficacy and Safety of Tarlatamab Versus Investigator-choice Chemotherapy in Pre-treated Patients With Advanced, Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine Carcinomas (NECs)
Based on the efficacy of tarlatamab in patients with small-cell lung cancer, we aim to assess the efficacy of tarlatamab in patients with Advanced, pulmonary (large-cell only) or gastroenteropancreatic neuroendocrine carcinoma.
• 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
• Age ≥ 18 years.
• WHO Performance status 0 - 1.
• Life expectancy \> 12 weeks.
• 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).
• Expression of DLL3 in at least 1% of tumor cells (assessed on archived tissue, with possible pre-screening during first-line)
• Tumor progression following one platinum based line of therapy.
• Unresectable locally advanced or metastatic stage.
• 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.
⁃ 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.
⁃ 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.
⁃ Availability of tumor material for central review processes and translational research projects.
⁃ 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.
⁃ 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 investigational product; 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 investigational product.
⁃ 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 treatment.
⁃ Patient covered by a national health insurance.