A Study of IDE849 in Patients With DLL3 Expressing Tumors Including Small Cell Lung Cancer

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 extensive-stage SCLCneuroendocrine carcinoma (NEC), and other DLL3+ tumors, are eligible per protocol.Subjects must have radiologically progressed or recurred after previous standardtreatment, For SCLC, this includes platinum-based therapy and programmeddeath-1/programmed death-ligand 1 inhibitors (except for subjects who refuse or arejudged by the Investigator to be unsuitable for immunotherapy). No more than 2 linesof previous systemic chemotherapy in any setting and no more than 3 total lines ofsystemic therapy in the recurrent or metastatic setting will be allowed.

3. Subjects will be required to provide blood/tumor tissue samples for biomarkertesting.

4. Have at least 1 measurable lesion according to RECIST version 1.1.

5. Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or

7. Have life expectancy > 3 months.

8. Have adequate bone marrow and organ function.

9. Women of childbearing potential must agree to take highly effective contraceptivemeasures from signing of consent through 8 months after the last dose of IDE849; menwith partners of child-bearing potential must use effective contraception through 5months after the last dose.

Exclusion Criteria:

1. Have mixed SCLC and nonsmall cell lung cancer histology (SCLC with components oflarge cell neuroendocrine carcinoma are eligible).

2. Subjects with locally untreated (radiotherapy or surgery) or active central nervoussystem (CNS) tumor metastasis.

3. Have had other malignancies within 2 years prior to the first dose, exceptadequately treated carcinoma in situ (cervical, breast, or other), basal cell orsquamous cell skin cancer, localized prostate cancer after curative therapy with norecurrence, or papillary thyroid cancer after curative resection; other prior orconcurrent 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 firststudy dose.

7. Have history of interstitial pneumonitis during previous treatment; currentnoninfectious pneumonitis requiring steroid therapy; known or suspected interstitialpneumonitis as seen on screening imaging; other moderate to severe lung diseasesseriously affecting respiratory function within 3 months before the first dose,including, but not limited to, idiopathic pulmonary fibrosis and organizingpneumonia/obliterative bronchiolitis.

8. Have history of immunodeficiency, with a positive human immunodeficiency virus (HIV)test.

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 havehad any prior Grade 2 or higher myocarditis or any other Grade 3 or higherimmune-related AE. If the participant has had a prior immune-related AE, must haverecovered to < Grade 1

12. For participants enrolling to receive the combination with IDE161, must not have hadprior gastrectomy or upper bowel removal or any other gastrointestinal disorder ordefect eg, malabsorption disorder such as Crohn's disease or ulcerative colitis,that would interfere with absorption of IDE161

13. Have received chemotherapy within 3 weeks of first dose of IMP; immunotherapy orbiologic targeted anti-tumor treatments within 2 weeks before the first dose of IMP;for small molecule treatments within 2 weeks before the first dose of the IMP orwithin 5 half lives of the drug (whichever is longer); other investigationalproducts 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 notinterfere with the study. Participants who received an immunotherapy agent (eg,PD-1/PD-L1 inhibitor) immediately prior to study enrollment must have documentedradiologic disease progression as per the Investigator prior to first dose of IMP

14. Administration of any of the following:

• Strong inhibitors or inducers of CYP3A4

• Strong inhibitors of CYP2D6

• Strong inhibitors of P-gp or BCRP

• Use of drugs with a known risk of QT prolongation

15. For participants enrolling to receive the combination with IDE161:

• Use of drugs of narrow therapeutic index that are sensitive substrates ofMATE2-K, BCRP, and P-gp

• Use of known moderate and strong CYP3A4/5 inducers and inhibitors is notpermitted

• Administration of PPIs

• Use of an H2 blocking agent

• Use of a local antacid

• Use of drugs with a known risk of QT prolongation

16. Have prior treatment with DLL3 ADC or prior treatment with a topoisomerase Iinhibitor including an ADC with a topoisomerase I inhibitor payload.

17. For participants enrolling to receive the combination with durvalumab, have historyof prior intolerance to PD-1/PD-L1 inhibitors

18. Have received > 30 Gy of chest radiotherapy within 12 weeks prior to the first doseof the IMP, > 30 Gy of non-chest radiotherapy within 4 weeks prior to the first dose (subjects who have completed radiotherapy for brain metastases within 14 days priorto 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).

19. Have undergone major surgery or experienced significant trauma within 4 weeks priorto the first dose.

20. Female subjects who are pregnant, lactating, or planning to become pregnant duringthe study period to 8 months after the last dose of the IMP.