• Age ≥18 years

• Patients with histologically confirmed diagnosis of metastatic/locally advanced SCLC with any level of DLL3 expression (Cohort 1) or other poorly differentiated NECs whatever the primary or high-grade MTC (Cohort 2) based on the most recent biopsy of a metastatic site. Tumors from Cohort 2 must be DLL3 positive defined as DLL3 ≥1% or H-score ≥1 by IHC

• For patients with poorly differentiated NECs whatever the primary, the biopsy of the disease diagnosis should be reviewed by an expert pathologist. Large cell, small cell or not otherwise specified are eligible. In addition, the tumor must have a Ki67 \>20% or mitotic rate \>20 per 10 high-power fields. For prostate cancer, the diagnosis of NEPC must be based on phenotype analysis, which may include IHC markers such as neuron-specific enolase (NSE), Chromogranin A or CD56 in the majority of the tumor sample, or molecular alterations such as TP53, Rb1, and PTEN

• High-grade MTC should be defined according to international medullary cancer grading system (IMCGS)

• Patients with metastatic/locally advanced SCLC and other poorly differentiated NECs must have been treated with at least 1 line of prior therapy, including a platinum-based regimen (resistant or sensitive to platinum), have experienced progression on standard treatment, as determined by the investigator. Prior treatment with PD-(L) 1 inhibitors is allowed Specific cases: Patients with NEPC must have received at least 1 line of prior therapy, including a platinum containing regimen for de novo NEPC or an androgen signaling inhibitor (eg. abiraterone, enzalutamide, darolutamide and/or apalutamide) if treatment-emergent NEPC. Patients with high-grade MTC (capped at 4 patients) must have been treated with at least 1 prior therapy including a RET selective inhibitor if the presence of a RET mutation

• Patients with NEPC and without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue therapy during the course of protocol therapy

• Patients must have an ECOG performance status ≤2 at the time of screening

• Patients must have a minimum life expectancy of 3 months

• Patients must have at least one radiologically measurable lesion according to response evaluation criteria in solid tumors (RECIST) v1.1 criteria

⁃ Patients must have a tumor site easily accessible to biopsy, avoiding bone biopsy when possible. Patient must have accepted to perform pre-treatment, on-treatment, and end-of-treatment tumor and blood biopsies

⁃ Patients must have adequate bone marrow reserve and organ function, based on local laboratory data within 21 days prior to cycle 1, day 1 defined as:

∙ Platelet count ≥100 000/mm3 or ≥100 × 109/L (platelet transfusions are not allowed up to 14 days prior to cycle 1 Day 1 to meet eligibility)

‣ Hemoglobin (Hgb) ≥9.0 g/dL (transfusion and/or growth factor support is allowed)

‣ Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 × 109/L (use of growth factors is not allowed in the 14 days prior cycle 1)

‣ Creatinine clearance (CrCl): Creatinine clearance (CrCl) ≥30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl; confirmation of CrCl is only required when SCr is \>1.5 × ULN

‣ Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and alkaline phosphatase (ALP) \<3 x ULN (or \<5 x ULN for patients with liver metastases)

‣ Total bilirubin (TBL) \<.5 x ULN (\<3 x ULN in the presence of documented Gilbert's Syndrome \[unconjugated hyperbilirubinemia\]) or \<2 X ULN for patients with liver metastases

‣ Serum albumin ≥2.5 g/dL

‣ Prothrombin time (PT) or Prothrombin time- international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT)≤1.5 × (ULN), except for patients on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator

⁃ Patients must have baseline oxygen saturation \> 90% on room air

⁃ Females of reproductive/childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 60 days for females after the last dose of study drug.

⁃ Note : Methods considered as highly effective methods of contraception include:

∙ Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

⁃ Oral

• Intravaginal

• Transdermal

∙ Progestogen-only hormonal contraception associated with inhibition of ovulation:

⁃ Oral

• Injectable

• Implantable

∙ Intrauterine device (IUD)

∙ Intrauterine hormone-releasing system (IUS)

∙ Bilateral tubal occlusion

∙ Vasectomized partner

∙ Complete sexual abstinence defined as refraining from heterosexual intercourse during and upon completion of the study and for at least 7 months for females after the last dose of study drug. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception

⁃ Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 60 days after the final study drug administration

⁃ Male patients must be surgically sterile or must withhold heterosexual intercourse or must be willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 60 days following the last dose of study drug

⁃ Male patients must not freeze or donate sperm starting at screening and throughout the study period, and at least 60 days after the final study drug administration

⁃ Patients must understand, sign and date the written informed consent from prior to any protocol-specific procedures performed. Patients should be able and willing to comply with study visits and procedures as per protocol

⁃ Patients must be affiliated to a Social Security System or beneficiary of the same