RECRUITING

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

Conditions

Limited Stage Small Cell Lung Cancer limited stage small cell lung carcinoma LS-SCLC Limited-stage SCLC Nivolumab Opdivo fucosyl-monosialoganglioside-1 fuc-GM1 programmed cell death protein 1 PD-1 inhibitor anti-PD-1 antibody Durvalumab Imfinzi PD-L1 inhibitor Anti-PD-L1 antibody Limited-stage (LS)-small-cell lung cancer (SCLC)BMS-986489

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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)

Quick Facts

Study Start:2025-03-11

Study Completion:2032-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06773910

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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

Inclusion Criteria

Exclusion 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.

* 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

Contacts and Locations

Study Contact

Sarah Cannon Development Innovations, LLC

CONTACT

1-844-710-6157

SCRI.InnovationsMedical@scri.com

Principal Investigator

Melissa Johnson, MD

STUDY_CHAIR

SCRI Development Innovations, LLC

Study Locations (Sites)

Sansum Clinic

Santa Barbara, California, 93105

United States

Cancer Care Centers of Brevard

Palm Bay, Florida, 32901

United States

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005

United States

Minnesota Oncology Hematology

Maple Grove, Minnesota, 55369

United States

Oncology Hematology Care

Cincinnati, Ohio, 45242

United States

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

Eugene, Oregon, 97401

United States

SCRI Oncology Partners

Nashville, Tennessee, 37203

United States

Texas Oncology - West Texas

Amarillo, Texas, 79124

United States

Texas Oncology - Gulf Coast

Beaumont, Texas, 77702

United States

Texas Oncology - DFW

Dallas, Texas, 75246

United States

Texas Oncology - San Antonio

San Antonio, Texas, 78240

United States

Texas Oncology - Northeast Texas

Tyler, Texas, 75702

United States

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

Salem, Virginia, 24153

United States

Collaborators and Investigators

Sponsor: SCRI Development Innovations, LLC

Melissa Johnson, MD, STUDY_CHAIR, SCRI Development Innovations, LLC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03-11

Study Completion Date2032-09

Study Record Updates

Study Start Date2025-03-11

Study Completion Date2032-09

Terms related to this study

Keywords Provided by Researchers

limited stage small cell lung cancer
limited stage small cell lung carcinoma
LS-SCLC
Limited-stage SCLC
Nivolumab
Opdivo
fucosyl-monosialoganglioside-1
fuc-GM1
programmed cell death protein 1
PD-1 inhibitor
anti-PD-1 antibody
Durvalumab
Imfinzi
PD-L1 inhibitor
Anti-PD-L1 antibody
Limited-stage (LS)-small-cell lung cancer (SCLC)
BMS-986489

Additional Relevant MeSH Terms

Limited Stage Small Cell Lung Cancer