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RecruitingInterventionalPhase 2

An Open-label, Randomized Study of BMS-986489 (Atigotatug + Nivolumab Fixed-dose Combination) vs Durvalumab as Consolidation Therapy Following Chemoradiotherapy in Limited-stage Small-cell Lung Cancer (TIGOS-LS)

NCT ID: NCT06773910Sponsor: SCRI Development Innovations, LLCLast updated: 2026-04-22

Summary

This is an open-label, randomized study of BMS-986489 (atigotatug + nivolumab fixed-dose combination) vs durvalumab in limited-stage (LS)-small-cell lung cancer (SCLC) participants. The main goals of this study are to: * Evaluate the efficacy of BMS-986489 vs durvalumab * Evaluate the safety profile of BMS-986489

Detailed description

This is an open-label, randomized study of BMS-986489 (atigotatug + nivolumab fixed-dose combination) vs durvalumab as consolidation therapy following chemoradiotherapy in participants with limited-stage (LS)-small-cell lung cancer (SCLC). Participants will receive concurrent chemotherapy and radiotherapy according to standard guidelines for treatment of LS-SCLC without progressive disease prior to randomization. Eligible participants will be randomly assigned to receive either BMS-986489 (atigotatug + nivolumab as a fixed-dose combination; Arm A) or durvalumab (Arm B) as consolidation therapy. Atigotatug is a first-in-class, fully human IgG1 antibody being developed for the treatment of SCLC. Atigotatug specifically binds to fuc-GM1 on the tumor cell. Nivolumab is a monoclonal anti-PD-1 antibody. Combining atigotatug with another immunotherapy may provide enhanced antitumor effects.

Arms & interventions

  • DrugBMS-986489

    BMS-986489 (fixed dose combination of atigotatug + nivolumab) will be administered as an intravenous infusion to be given once every 4 weeks for up to 2 years.

  • DrugDurvalumab

    Durvalumab will be administered as a fixed dose intravenous infusion to be given once every 4 weeks for up to 2 years.

Outcome measures

Primary

  • Evaluate the efficacy of BMS-986489 vs durvalumab by Overall Survival (OS).

    Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause.

    Time frame: From date of randomization up to 5 years. Every 8 weeks for participants who stopped treatment before disease progression and before completing 6 months of treatment and every 12 weeks for participants who stopped treatment before disease progression and

Secondary

  • Evaluate the efficacy of BMS-986489 vs durvalumab by Progression Free Survival (PFS).

    Time frame: Every 2 cycles (8 weeks) from Cycle 1 Day 1, for the first 6 months, then every 3 cycles (12 weeks) until disease progression or death, up to 3 years. Each cycle is 28 days.

  • Evaluate the efficacy of BMS-986489 vs durvalumab Objective Response Rate (ORR).

    Time frame: Every 2 cycles (8 weeks) from Cycle 1 Day 1, for the first 6 months, then every 3 cycles (12 weeks) until disease progression or death, up to 3 years. Each cycle is 28 days.

  • Evaluate the efficacy of BMS-986489 vs durvalumab by Clinical Benefit Rate (CBR).

    Time frame: Every 2 cycles (8 weeks) from Cycle 1 Day 1, for the first 6 months, then every 3 cycles (12 weeks) until disease progression or death, up to 3 years. Each cycle is 28 days.

  • Evaluate the efficacy of BMS-986489 vs durvalumab by Disease Control Rate (DCR).

    Time frame: Every 2 cycles (8 weeks) from Cycle 1 Day 1, for the first 6 months, then every 3 cycles (12 weeks) until disease progression or death, up to 3 years. Each cycle is 28 days.

  • Evaluate the efficacy of BMS-986489 vs durvalumab by Duration of Response (DoR).

    Time frame: Every 2 cycles (8 weeks) from Cycle 1 Day 1, for the first 6 months, then every 3 cycles (12 weeks) until disease progression or death, up to 3 years. Each cycle is 28 days.

  • Evaluate the efficacy of BMS-986489 vs durvalumab by Time to Progression (TtP).

    Time frame: Every 2 cycles (8 weeks) from Cycle 1 Day 1, for the first 6 months, then every 3 cycles (12 weeks) until disease progression or death, up to 3 years. Each cycle is 28 days.

  • Evaluate the efficacy of BMS-986489 vs durvalumab by time to development of central nervous system (CNS) metastasis.

    Time frame: Every 2 cycles (8 weeks) from Cycle 1 Day 1, for the first 6 months, then every 3 cycles (12 weeks) until disease progression or death, up to 3 years. Each cycle is 28 days.

  • Evaluate the number of participants with adverse events following administration of BMS-986489.

    Time frame: From Cycle 1 Day 1 to 100 days after the last dose of BMS-986489. Each cycle is 28 days.

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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) scan prior to initiation of chemotherapy and radiation therapy * Completed concurrent chemotherapy and radiotherapy for LS-SCLC without progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (computed tomography \[CT\] scan chest/abdomen/pelvis; Appendix B) within 42 days before date of randomization and first dose of study treatment * Chemotherapy should consist of a platinum and IV etoposide. Participants who received 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 the Investigator and institutional guidelines. PCI, if applicable, must be conducted after the end of chemoradiotherapy and completed between 14 and 42 days before date of randomization and first dose of study treatment. * Adequate hematologic and organ function * Willingness to abide by protocol defined contraceptive requirements for the duration of 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) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 * Active, prior, or suspected autoimmune disease, including autoimmune neurologic disorders such as paraneoplastic syndrome involving the CNS, peripheral sensory/motor nerves, or neuromuscular junction. Exceptions to this criterion include: * 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 daily prednisone or equivalent) or other immunosuppressive therapy within 14 days of starting study treatment. Limited-course (\<2 weeks' duration) oral steroids (10 mg prednisone or equivalent) are permitted. Bronchodilators, inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone equivalent are 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) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third-degree heart block, atrial fibrillation not rate controlled. Certain conditions may be considered through discussion with the Medical Monitor. * Congestive heart failure (New York Heart Association \[NYHA\] \> Grade 2) or classified as Class 3 or 4 by the NYHA Functional Classification (Appendix D) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, uncontrolled hypokalemia, congenital long QT syndrome, 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 the Medical Monitor. * Participants with a left ventricular ejection fraction \<55% or the lower limit of normal of the institutional standard * Uncontrolled hypertension, defined as systolic blood pressure \>150 mmHg or diastolic 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 medical disorders * Presence of other active invasive cancers. Participants with a previously treated malignancy will be eligible to participate if treatment of that malignancy was completed at least 2 years before date of screening and the participants has no evidence of disease. Exceptions to this criterion include appropriately treated basal cell carcinoma of the skin; in situ carcinoma of uterine cervix; localized prostate cancer that has been definitively treated; or other local tumors considered cured by local treatment. * Received sequential chemotherapy and radiotherapy as a definitive treatment for LS-SCLC * Treatment with any of the following: * Any systemic anticancer chemotherapy, small molecule, biologic, or hormonal agent from a previous treatment regimen or clinical study within 21 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment * Wide-field radiotherapy (including therapeutic radioisotopes such as strontium-89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study treatment or has not recovered from side effects of such therapy * Prior systemic treatment for LS-SCLC, with the exception of chemoradiotherapy and PCI * Prior treatment with an anti-PD-1, anti-PD-L1, anti-programmed cell death ligand 2 (anti-PD-L2), anti-CD137, anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways * Prior treatment with fuc-GM-1 vaccine or targeted agent or similar vaccine targeting 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 of screening * With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment. Note: Participants with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be eligible with approval by the Medical Monitor or Principal Investigator. * Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol

Study locations (33)

Southern Cancer Center

Daphne, Alabama, 36526

Recruiting

Sansum Clinic

Santa Barbara, California, 93105

Recruiting

Florida Cancer Specialists - South

Fort Myers, Florida, 33901

Recruiting

University of Miami - Sylvester Cancer Center

Miami, Florida, 33136

Active Not Recruiting

Ocala Oncology Center

Ocala, Florida, 34474

Recruiting

Florida Cancer Specialists - North

Orange City, Florida, 32763

Recruiting

Cancer Care Centers of Brevard

Palm Bay, Florida, 32901

Recruiting

Florida Cancer Specialists - East

West Palm Beach, Florida, 33401

Recruiting

Piedmont Healthcare - Atlanta

Atlanta, Georgia, 30309

Recruiting

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005

Recruiting

Illinois Cancer Care

Peoria, Illinois, 61615

Recruiting

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202

Recruiting

Baptist Health - Corbin

Corbin, Kentucky, 40701

Recruiting

Baptist Health - Lexington

Lexington, Kentucky, 40503

Recruiting

Baptist Health - Louisville

Louisville, Kentucky, 40207

Recruiting

Minnesota Oncology Hematology

Maple Grove, Minnesota, 55369

Recruiting

Missouri Cancer Associates

Columbia, Missouri, 65201

Recruiting

White Plains Hospital Physician Associates

White Plains, New York, 10601

Recruiting

Carolina Cancer Research Center

Wilson, North Carolina, 27896

Recruiting

Oncology Hematology Care

Cincinnati, Ohio, 45242

Recruiting

Mid Ohio Hem/ Onc dba The Mark H Zangmeister Center

Columbus, Ohio, 43219

Recruiting

Oncology Associates of Oregon (Willamette Valley Cancer Institute and Research Center)

Eugene, Oregon, 97401

Recruiting

Tennessee Cancer Specialists

Knoxville, Tennessee, 37909

Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting

Texas Oncology - West Texas

Amarillo, Texas, 79124

Recruiting

Texas Oncology- Austin

Austin, Texas, 78705

Recruiting

Texas Oncology - Gulf Coast

Beaumont, Texas, 77702

Recruiting

Texas Oncology - DFW

Dallas, Texas, 75246

Recruiting

Texas Oncology - Northeast Texas

Denison, Texas, 75020

Recruiting

Texas Oncology - San Antonio

San Antonio, Texas, 78240

Recruiting

Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting

Virginia Oncology Associates

Norfolk, Virginia, 23502

Recruiting

Blue Ridge Cancer Center (Oncology & Hematology Associates of Southwest VA)

Salem, Virginia, 24153

Recruiting