Tarlatamab in Advanced Delta-like 3 (DLL3)-Expressing Tumors Including Neuroendocrine Neoplasms

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Participant has provided informed consent prior to initiation of any study specificactivities/procedures.

2. Male or female ≥ 18 years of age and willing and able to provide informed consent.

3. Histologically or cytologically confirmed malignancy other than de novo (i.e.,non-transformed) SCLC or NEPC. Must be stage IV (metastatic); participants withstage III disease are eligible provided that they are not candidates for surgeryand/or radiotherapy with curative intent. Acceptable tumor types include thefollowing:

• Low and intermediate grade neuroendocrine carcinoma (including carcinoid andatypical carcinoid)

• Gastroenteropancreatic NEN

• Large cell neuroendocrine carcinoma

• SCLC transformed from previously-treated NSCLC

• Extrapulmonary small cell carcinoma, with the exception of NEPC

• Any other tumor type that meets staging and DLL3 positivity criteria

4. Positive DLL3 expression by immunohistochemistry on tumor biopsy.

• Positive DLL3 expression, for purposes of this study, defined as at least 25% forparticipants enrolling into Stage 1 or 1% for participants enrolling into Stage 2.

5. Participants must have progressed on or following at least one line of therapy, if astandard of care therapy exists for the tumor type.

6. Measurable disease, as per RECIST 1.1

7. ECOG performance status of 0-1.

8. Adequate organ function as defined in Table 3 below. System Laboratory ValueHematological Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelets ≥ 100 x 109/LHemoglobin ≥ 9 g/dL Renal Estimated glomerular filtration rate (eGFR) based onModification of Diet in Renal Disease (MDRD) ≥ 30 mL/min/1.73 m2 Hepatic Serum totalbilirubin ≤ 1.5 x ULN, with the exception of participants with Gilbert's disease AST (SGOT) and ALT (SGPT) ≤ 3 x ULN≤ 5 x ULN for patients with liver metastasis orprimary liver cancer Coagulation International Normalized Ratio (INR) or ProthrombinTime (PT), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unlessparticipant is receiving anticoagulant therapy, and then only as long as PT or PTTis within therapeutic range of intended use of anticoagulants

Exclusion Criteria:

Disease Related

1. Diagnosis of SCLC (with the exception of SCLC transformed from previously-treatedNSCLC) or NEPC.

2. Tumor specimen is not evaluable for DLL3 expression or tumor has DLL3 surfaceexpression < 1% by immunohistochemistry.

3. Progressive or symptomatic brain metastases. Brain metastases that have beenradiated, are asymptomatic, and on a stable or decreasing dose of steroids areallowed. Leptomeningeal disease is excluded.

4. Evidence of interstitial lung disease or active, non-infectious pneumonitis.Exception: pneumonitis related to prior radiation therapy that is grade 1 and stableor improving without treatment. Prior/Concomitant Therapy

5. Concurrent enrollment in another clinical study, unless enrolled only in thefollow-up period or an observational study. Use of any investigational anticancertherapy must not have been received within 28 days prior to the first dose of studydrugs.

6. Any chemotherapy, antibody drug conjugate or immunotherapy for cancer treatment inthe prior 21 days, or small molecular inhibitor in the prior 7 days.

• Stereotactic, palliative radiation for symptomatic bone metastases is acceptablewithout a washout.

• Stereotactic brain radiation for asymptomatic brain metastases is acceptable witha 7-day washout.

7. Prior therapy with any selective inhibitor of the DLL3 pathway.

8. Prior history of severe or life-threatening events from any immune-mediated therapy.

9. Receiving systemic corticosteroid therapy or any other form of immunosuppressivetherapy within 7 days prior to enrollment. Low-dose corticosteroids (prednisone ≤ 10mg per day or equivalent is permitted)

10. Major surgical procedures within 28 days prior to first dose of study treatment.

11. Treatment with live virus, including live-attenuated vaccination, within 14 daysprior to the first dose of study treatment. Inactive vaccines (e.g., non-live ornon-replicating agent) and live viral non-replicating vaccines within 3 days priorto first dose of study treatment. Other Medical Conditions

12. History of other malignancy within the past 2 years, with the following exceptions:

• Malignancy treated with curative intent before enrollment, with no known activedisease and felt to be at low risk for recurrence by the treating physician, afterdiscussion with the medical monitor.

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidenceof disease.

• Adequately treated cervical carcinoma in situ without evidence of disease.

• Adequately treated breast ductal carcinoma in situ without evidence of disease.

• Prostatic intraepithelial neoplasia without evidence of prostate cancer.

• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma insitu.

13. History of myocardial infarction and/or symptomatic congestive heart failure (NewYork Heart Association, class II) within 6 months prior to first dose of studytreatment.

14. History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6months prior to first dose of study treatment.

15. Human immunodeficiency virus (HIV) infection.

• Participants with HIV infection on antiviral therapy and undetectable viral loadare permitted with a requirement for regular monitoring for reactivation for theduration of treatment on study per local or institutional guidelines

16. Active hepatitis C infection.

• Defined as participants with detectable hepatitis C antibody [HCV Ab] andhepatitis C virus [HCV] RNA viral load above the limit of quantification

• Participants with presence of HCV antibody (HCV Ab positive) and HCV RNA viralload below the limit of quantification (HCV RNA negative) with or without priortreatment are allowed

17. Active hepatitis B infection. • Defined as presence of hepatitis B surface antigen [HBsAg-positive] and hepatitis B virus [HBV] DNA viral load above the limit ofquantification [HBV DNA positive] • Participants with resolved HBV infection definedas absence of HBV surface antigen (HBsAg-negative) and presence of HBV core antibody (anti-HBc positive) followed by an HBV DNA viral load below the limit ofquantification (HBV DNA negative) are allowed, with a requirement for regularmonitoring for reactivation for the duration of treatment on the study and assessingthe need for HBV prophylaxis therapy per local or institutional guidelines.

• Participants with chronic HBV infection inactive carriers state, defined aspresence of HBV surface antigen (HBsAg-positive) and HBV DNA viral load below thelimit of quantification (HBV DNA negative) are allowed, with a requirement forregular monitoring for reactivation for the duration of treatment on the study andassessing the need for HBV prophylaxis therapy per local or institutionalguidelines.

18. Participants with symptoms and/or clinical signs and/or radiographic signs thatindicate an acute and/or uncontrolled active systemic infection within 7 days priorto the first dose of study treatment.

• Upon completion of antibiotics and resolution of symptoms, the participant maybe considered eligible for the study from an infection standpoint.

• Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitisare permitted if responding to active treatment. Participants requiring oralantibiotics who have been afebrile > 24 hours, have no leukocytosis, norclinical signs of infection are eligible. Screening for chronic infectiousconditions is not required unless otherwise noted as exclusion criteria. Other Exclusions

19. Female participants of childbearing potential unwilling to use protocol specifiedmethod of contraception (see Section 5.7.2) during treatment and for an additional 60 days after the last dose of study treatment.

20. Female participants who are breastfeeding or who plan to breastfeed while on studythrough 60 days after the last dose of study treatment.

21. Female participants planning to become pregnant or donate eggs while on studythrough 60 days after the last dose of study treatment.

22. Female participants of childbearing potential with a positive pregnancy testassessed at screening by a highly sensitive serum pregnancy test.

23. Male participants with a female partner of childbearing potential who are unwillingto practice sexual abstinence (refrain from heterosexual intercourse) or usecontraception during treatment and for an additional 60 days after the last dose.

24. Male participants with a pregnant partner who are unwilling to practice abstinenceor use a condom during treatment and for an additional 60 days after the last doseof study treatment.

25. Male participants unwilling to abstain from donating sperm during treatment and foran additional 60 days after the last dose of study treatment.

26. Participant has known sensitivity to any of the products or components to beadministered during dosing.

27. Participant likely to not be available to complete all protocol-required studyvisits or procedures, and/or to comply with all required study procedures (e.g.,Clinical Outcome Assessments) to the best of the participant's and investigator'sknowledge.

28. History or evidence of any other clinically significant disorder, condition, ordisease (with the exception of those outlined above) that, in the opinion of theinvestigator, if consulted, would pose a risk to participant safety or interferewith the study evaluation, procedures or completion.