Overview
Researchers are looking for new ways to treat extensive-stage small cell lung cancer (ES-SCLC). ES-SCLC is a type of lung cancer that has spread throughout the lung, to the other lung, or to other parts of the body.
A standard (usual) treatment for ES-SCLC uses both chemotherapy and immunotherapy.
- Chemotherapy is a treatment that works to destroy cancer cells or stop them from growing.
- Immunotherapy is a treatment that helps the immune system fight cancer.
Gocatamig and I-DXd (short for ifinatamab deruxtecan) are study medicines. Researchers want to know if giving gocatamig and I-DXd together can treat ES-SCLC. Researchers will also look at giving the study medicines with standard treatment. Gocatamig is a T-cell engager therapy. I-DXd is an antibody drug conjugate.
- T-cell engager therapy is a certain type of immunotherapy that uses T-cells to find and destroy cancer cells.
- A T-cell is a type of white blood cell, which are cells that help the body fight infection.
- An antibody drug conjugate (ADC) is a treatment that attaches to a protein on cancer cells and delivers treatment to destroy those cells.
The goals of this study are to learn:
- About the safety of combining gocatamig and I-DXd and if people tolerate them together
- If people who receive gocatamig and I-DXd have ES-SCLC respond, which means the cancer gets smaller or goes away
Description
In Part A, participants will be allocated to Arm 1 or Arm 2 per investigator's discretion. In Part B, participants will be allocated to Arm 1 per investigator's discretion and randomized to Arms 2, 3, and 4.
Eligibility
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
- Has a histologically or cytologically confirmed diagnosis of extensive-stage small cell lung cancer (ES-SCLC)
- For participants receiving gocatamig + ifinatamab deruxtecan (I-DXd) in maintenance only:
- Completed 3 to 4 cycles of platinum + etoposide chemotherapy with concurrent approved anti-programmed cell death 1/Ligand 1 (anti PD-1/L1) as first line (1L) treatment of ES-SCLC within 6 weeks prior to enrollment
- No radiological disease progression per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
- No other prior systemic ES-SCLC therapy allowed
- Rechallenge therapy counts as an additional line and leads to exclusion
- For participants receiving gocatamig + I-DXd in induction and maintenance, or gocatamig + I-DXd in induction followed by gocatamig + atezolizumab in maintenance, or carboplatin + etoposide + atezolizumab in induction followed by atezolizumab in maintenance: No prior systemic ES-SCLC treatment allowed
- Applicable to all participants: prior limited-stage small cell lung cancer (SCLC) is allowed if \> 6 months have passed since the end of previous therapy and progression
- Must be able to provide a pretreatment archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated
- Measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if growth has been shown in such lesions since the completion of radiation
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
- Has pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, current ILD, ILD that cannot be ruled out by imaging at screening, or suspected ILD
- Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
- Has history of clinically significant intracranial bleeding or spinal cord bleeding
- Has active neurologic paraneoplastic syndrome
- Has history of coronary/peripheral artery bypass graft and/or any coronary/peripheral angioplasty or clinically significant cardiovascular disease such as myocardial infarction, symptomatic congestive heart failure (CHF), and/or uncontrolled cardiac arrhythmia within 6 months before the first dose of study intervention
- Has other uncontrolled or significant protocol specified cardiovascular disease
- Has history of arterial thrombosis within 6 months before the first dose of study intervention
- Has chronic liver disease
- Has history of allogeneic tissue/solid organ transplant
- Has history of leptomeningeal disease
- Is infected with human immunodeficiency virus (HIV) and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
- Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has major surgery within 4 weeks or minor surgery within 2 weeks of allocation/randomization (or first dose), or is anticipated to require a major surgical procedure during the study
