IDE849 for DLL3-Expressing Tumors

Inclusion Criteria: 1. Are willing to participate in this clinical study, understand the study procedures, and are able to sign the written ICF. 2. Subjects with histologically or cytologically confirmed ES- SCLC, neuroendocrine carcinoma (NEC), DLL3+ solid tumors, are eligible per protocol. Subjects must have radiologically progressed or recurred after previous standard treatment. For SCLC, this includes platinum-based therapy and programmed death-1/programmed death-ligand 1 inhibitors (except for subjects who refuse, or are judged by the Investigator to be unsuitable, or were intolerant to immunotherapy and chemotherapy may enroll to receive monotherapy or IDE161 combination. 3. Subjects with NEC, this includes * High-grade gastroenteropancreatic NEC * NEC of the prostate * Small cell NEC of any other organ * Merkel cell carcinoma * Transformed non-small cell adenocarcinoma of the lung (including but not limited to epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene homolog mutated adenocarcinoma of the lung post progression on targeted therapies * Any other NEC that does not meet any of the indications noted above. 4. Subjects with other solid tumors demonstrated to express moderate/high expression of DLL3 including metastatic melanoma, Grade 3 gastrointestinal and pancreatic NETs, and pulmonary carcinoids. • metastatic melanoma 5. Subjects will be required to provide blood/tumor tissue samples for biomarker testing. 6. Have at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 7. Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1. 8. Have life expectancy \> 3 months. 9. Have adequate bone marrow and organ function within 7 days of the first dose (no use of any blood components and/or cell growth factors within 14 days prior to the start of the study treatment). 10. Women of childbearing potential (WOCBP) must agree to take highly effective contraceptive measures from signing of consent through 8 months after the last dose of IDE849; men with partners of child-bearing potential must use effective contraception through 5 months after the last dose. Exclusion Criteria: 1. Have mixed SCLC and NSCLC histology are not allowed (SCLC with components of large cell NEC are eligible). Participants with limited stage SCLC are ineligible. 2. Subjects with locally untreated (radiotherapy or surgery) or active central nervous system (CNS) tumor metastasis. 3. Have had other malignancies within 2 years prior to the first dose, except adequately treated carcinoma in situ (cervical, breast, or other), basal cell or squamous cell skin cancer, localized prostate cancer after curative therapy with no recurrence, or papillary thyroid cancer after curative resection; other prior or concurrent malignancies may be eligible with Medical Monitor review and approval. 4. Have uncontrolled tumor-associated pain. 5. Have severe cardiovascular and cerebrovascular disease 6. Have history of clinically significant bleeding within 3 months before the first study dose. 7. Have history of interstitial pneumonitis during previous treatment; current noninfectious pneumonitis requiring steroid therapy; known or suspected interstitial pneumonitis as seen on screening imaging; other moderate to severe lung diseases seriously affecting respiratory function within 3 months before the first dose, including, but not limited to, idiopathic pulmonary fibrosis and organizing pneumonia/obliterative bronchiolitis. 8. Have history of immunodeficiency, with a positive human immunodeficiency virus (HIV) test at screening (HIV antibody positive and HIV-RNA above the lower limit of detection of the analytical method). 9. Subjects with known or suspected viral hepatitis. 10. Have a history of active tuberculosis within 1 year before enrollment. 11. For participants enrolling to receive the combination with durvalumab, must not be deemed by the Investigator to be unsuitable to receive immunotherapy, or have had any prior intolerance to PD-1/PD-L1 inhibitor therapy, or have had any prior Grade 2 or higher myocarditis or any other Grade 3 or higher immune-related AE. If the participant has had a prior immune-related AE, must have recovered to Grade \< 1. 12. For participants enrolling to receive the combination with IDE161, must not have had prior GI or upper bowel removal or any other gastrointestinal disorder or defect (eg, malabsorption disorder such as Crohn's disease or ulcerative colitis), that would interfere with absorption of IDE161. 13. For patients receiving a combination with carboplatin, be deemed by the Investigator to be unsuitable to receive platinum-based chemotherapy, or have had intolerance to platinum-based chemotherapy 14. Have received chemotherapy within 3 weeks of first dose of IMP; immunotherapy or biologic targeted antitumor treatments within 2 weeks before the first dose of IMP; for small molecule treatments within 2 weeks before the first dose of the IMP or within 5 half lives of the drug (whichever is longer); other investigational products within 4 weeks or within 5 half-lives of the drug (whichever is longer) unless, in the opinion of the Investigator and Sponsor, the medication will not interfere with the study. Participants who received an immunotherapy agent (eg, PD-1/PD-L1 inhibitor) immediately prior to study enrollment must have documented radiologic disease progression as per the Investigator prior to the first dose of IMP 15. Administration of any of the following: * Use of drugs that are inhibitors of P-gp, BCRP, and OATPIB1/OATP1B3 * Use of drugs with known risk of QT prolongation within 5 half-lives of their administration. 16. For participants enrolling to receive the combination with IDE161: * Use of drugs of narrow therapeutic index that are sensitive substrates of MATE2-K, BCRP, and P-gp * Use of known moderate and strong CYP3A4/5 inducers and inhibitors is not permitted * Administration of PPIs * Use of an H2 blocking agent * Use of a local antacid * Use of drugs with a known risk of QT prolongation 17. Have prior treatment with DLL3 ADC with a Topo1 inhibitor payload (except for participants enrolling to receive the IDE161 combination). 18. For participants enrolling to receive the combination with durvalumab, have history of prior intolerance to PD-1/PD-L1 inhibitors. 19. Have received \> 30 Gy of chest radiotherapy within 8 weeks prior to the first dose of the IMP, \> 30 Gy of non-chest radiotherapy within 14 days prior to the first dose (subjects who have completed radiotherapy for brain metastases within 14 days prior to the first dose can be enrolled and palliative radiotherapy for other sites of ≤ 30 Gy is allowed if completed more than 14 days prior to the first dose). 20. Have undergone major surgery or experienced significant trauma within 4 weeks prior to the first dose. 21. Female subjects who are pregnant, lactating, or planning to become pregnant during the study period to 8 months after the last dose of the IMP.