BMS-986489 (Atigotatug + Nivolumab) vs Durvalumab in Limited-stage Small-cell Lung Cancer (TIGOS-LS)

Inclusion Criteria:

• At least 18 years-of-age at the time of signature of the Informed Consent Form (ICF)

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (Appendix A)

• Histologically or cytologically confirmed pulmonary SCLC, evaluable by RECIST v1.1

• Limited-stage (LS) disease as determined by positron emission tomography (PET) scanprior to initiation of chemotherapy and radiation therapy

• Completed concurrent chemotherapy and radiotherapy for LS-SCLC without progressionper Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (computed tomography [CT] scan chest/abdomen/pelvis; Appendix B) within 42 days before date ofrandomization and first dose of study treatment

• Chemotherapy should consist of a platinum and IV etoposide. Participants whoreceived at least 3 cycles of chemotherapy will be eligible to participate.

• Radiotherapy should be administered per institutional guidelines

• Prophylactic cranial irradiation (PCI) may be delivered at the discretion of theInvestigator and institutional guidelines. PCI, if applicable, must be conductedafter the end of chemoradiotherapy and completed between 14 and 42 days before dateof randomization and first dose of study treatment.

• Adequate hematologic and organ function

• Willingness to abide by protocol defined contraceptive requirements for the durationof the study.

Exclusion Criteria:

• Small-cell cancer not pulmonary in origin

• Large cell neuroendocrine carcinoma

• ES-SCLC

• Mixed SCLC and NSCLC histologic features; diagnosis of NSCLC; or EGFR-activating,mutation-positive NSCLC that has transformed to SCLC

• History of severe hypersensitivity reaction to monoclonal antibodies

• Known hypersensitivity to any excipients of atigotatug, nivolumab, or durvalumab

• Grade ≥2 peripheral neuropathy by the National Cancer Institute (NCI) CommonTerminology Criteria for Adverse Events (CTCAE) v5.0

• Active, prior, or suspected autoimmune disease, including autoimmune neurologicdisorders such as paraneoplastic syndrome involving the CNS, peripheralsensory/motor nerves, or neuromuscular junction. Exceptions to this criterioninclude:

• Type 1 diabetes mellitus

• Hypothyroidism requiring only hormone replacement

• Skin disorders not requiring systemic treatment

• Autoimmune conditions not expected to recur during the study

• Diseases or conditions requiring chronic systemic corticosteroids (>10 mg dailyprednisone or equivalent) or other immunosuppressive therapy within 14 days ofstarting study treatment. Limited-course (<2 weeks' duration) oral steroids (10 mgprednisone or equivalent) are permitted. Bronchodilators, inhaled or topicalsteroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalentare permitted in the absence of active autoimmune disease.

• History of solid organ or bone marrow transplantation

• History of Grade ≥2 pneumonitis (excepting resolved infective pneumonitis)

• Any of the following cardiac criteria, currently or within the last 3 months:

• Any clinically important abnormalities (as assessed by the Investigator) inrhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g.,complete left bundle branch block, third-degree heart block, atrialfibrillation not rate controlled. Certain conditions may be considered throughdiscussion with the Medical Monitor.

• Congestive heart failure (New York Heart Association [NYHA] > Grade 2) orclassified as Class 3 or 4 by the NYHA Functional Classification (Appendix D)

• Any factors that increase the risk of QTc prolongation or risk of arrhythmicevents such as heart failure, uncontrolled hypokalemia, congenital long QTsyndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval (Appendix E). Certain conditions may be considered through discussion with theMedical Monitor.

• Participants with a left ventricular ejection fraction <55% or the lower limitof normal of the institutional standard

• Uncontrolled hypertension, defined as systolic blood pressure >150 mmHg ordiastolic blood pressure >90 mmHg despite optimal medical management

• Active coronary artery disease, including unstable or newly diagnosed angina

• Myocardial infarction

• History of clinically significant arrhythmias (such as ventricular tachycardia,ventricular fibrillation, or Torsade de Pointes)

• History or current diagnosis of myocarditis

• As judged by the Investigator, participants with serious or uncontrolled medicaldisorders

• Presence of other active invasive cancers. Participants with a previously treatedmalignancy will be eligible to participate if treatment of that malignancy wascompleted at least 2 years before date of screening and the participants has noevidence of disease. Exceptions to this criterion include appropriately treatedbasal cell carcinoma of the skin; in situ carcinoma of uterine cervix; localizedprostate cancer that has been definitively treated; or other local tumors consideredcured by local treatment.

• Received sequential chemotherapy and radiotherapy as a definitive treatment forLS-SCLC

• Treatment with any of the following:

• Any systemic anticancer chemotherapy, small molecule, biologic, or hormonalagent from a previous treatment regimen or clinical study within 21 days or 5half-lives (whichever is longer) prior to the first dose of study treatment

• Wide-field radiotherapy (including therapeutic radioisotopes such asstrontium-89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study treatment or has not recovered from sideeffects of such therapy

• Prior systemic treatment for LS-SCLC, with the exception of chemoradiotherapyand PCI

• Prior treatment with an anti-PD-1, anti-PD-L1, anti-programmed cell deathligand 2 (anti-PD-L2), anti-CD137, anti-cytotoxic T-lymphocyte associatedprotein 4 (anti-CTLA-4) antibody, or any other antibody or drug specificallytargeting T-cell costimulation or checkpoint pathways

• Prior treatment with fuc-GM-1 vaccine or targeted agent or similar vaccinetargeting ganglioside antigens

• Current treatment with immunosuppressive medications

• Live attenuated vaccine within 100 days before first dose of study treatment

• Major surgery (excluding placement of vascular access) within 4 weeks of date ofscreening

• With the exception of alopecia, any unresolved toxicities from prior therapy greaterthan CTCAE Grade 1 at the time of starting study treatment. Note: Participants withchronic Grade 2 toxicities who are asymptomatic or adequately managed with stablemedication may be eligible with approval by the Medical Monitor or PrincipalInvestigator.

• Psychological, familial, sociological, or geographical conditions that do not permitcompliance with the protocol and/or follow-up procedures outlined in the protocol