A Phase 1b/2 Open-label Study Evaluating Different MK-6070 and Ifinatamab Deruxtecan (MK-2400)-Based Regimens in First-line Extensive Stage Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 170
- 试验地点
- 52
- 主要终点
- Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm 2, Parts A and B: Gocataming + I-DXd
Participants who did not receive prior systemic treatment for ES-SCLC will receive gocatamig and I-DXd during induction and maintenance phases, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Rescue Medications (Drug)
Arm 1, Parts A and B: Gocataming + I-DXd
Participants who completed standard of care (SOC) induction chemotherapy with concurrent approved anti-programmed cell death 1/ligand 1 protein (anti-PD-1/L1) treatment for ES-SCLC and did not have disease progression per investigator discretion, will receive gocatamig and I-DXd in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: I-DXd (Drug)
Arm 3, Part B: Gocataming + I-DXd → gocatamig + atezolizumab
Participants who did not receive prior systemic treatment for ES-SCLC will receive gocatamig and I-DXd in the induction phase, followed by gocatamig and atezolizumab in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Gocatamig (Drug)
Arm 1, Parts A and B: Gocataming + I-DXd
Participants who completed standard of care (SOC) induction chemotherapy with concurrent approved anti-programmed cell death 1/ligand 1 protein (anti-PD-1/L1) treatment for ES-SCLC and did not have disease progression per investigator discretion, will receive gocatamig and I-DXd in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Gocatamig (Drug)
Arm 2, Parts A and B: Gocataming + I-DXd
Participants who did not receive prior systemic treatment for ES-SCLC will receive gocatamig and I-DXd during induction and maintenance phases, until documented disease progression or meeting other study discontinuation criteria.
干预措施: I-DXd (Drug)
Arm 4, Part B: Carboplatin + etoposide + atezolizumab → atezolizumab
Participants who did not receive prior systemic treatment for ES-SCLC will receive SOC (carboplatin + etoposide + atezolizumab) in the induction phase, followed by atezolizumab in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Etoposide (Drug)
Arm 2, Parts A and B: Gocataming + I-DXd
Participants who did not receive prior systemic treatment for ES-SCLC will receive gocatamig and I-DXd during induction and maintenance phases, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Gocatamig (Drug)
Arm 3, Part B: Gocataming + I-DXd → gocatamig + atezolizumab
Participants who did not receive prior systemic treatment for ES-SCLC will receive gocatamig and I-DXd in the induction phase, followed by gocatamig and atezolizumab in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: I-DXd (Drug)
Arm 3, Part B: Gocataming + I-DXd → gocatamig + atezolizumab
Participants who did not receive prior systemic treatment for ES-SCLC will receive gocatamig and I-DXd in the induction phase, followed by gocatamig and atezolizumab in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Atezolizumab (Drug)
Arm 4, Part B: Carboplatin + etoposide + atezolizumab → atezolizumab
Participants who did not receive prior systemic treatment for ES-SCLC will receive SOC (carboplatin + etoposide + atezolizumab) in the induction phase, followed by atezolizumab in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Carboplatin (Drug)
Arm 1, Parts A and B: Gocataming + I-DXd
Participants who completed standard of care (SOC) induction chemotherapy with concurrent approved anti-programmed cell death 1/ligand 1 protein (anti-PD-1/L1) treatment for ES-SCLC and did not have disease progression per investigator discretion, will receive gocatamig and I-DXd in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Rescue Medications (Drug)
Arm 3, Part B: Gocataming + I-DXd → gocatamig + atezolizumab
Participants who did not receive prior systemic treatment for ES-SCLC will receive gocatamig and I-DXd in the induction phase, followed by gocatamig and atezolizumab in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Rescue Medications (Drug)
Arm 4, Part B: Carboplatin + etoposide + atezolizumab → atezolizumab
Participants who did not receive prior systemic treatment for ES-SCLC will receive SOC (carboplatin + etoposide + atezolizumab) in the induction phase, followed by atezolizumab in the maintenance phase, until documented disease progression or meeting other study discontinuation criteria.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
时间窗: Up to approximately 21 days
DLT will be defined as any drug-related AE observed during the DLT evaluation period (up to 21 days) that meets the protocol-specified DLT criteria. The number of participants who experience at least one DLT will be presented.
Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 58 months
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
Number of Participants Who Discontinue Study Intervention Due to an AE
时间窗: Up to approximately 58 months
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study intervention due to an AE will be reported.
Objective Response Rate (ORR)
时间窗: Up to approximately 58 months
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
次要结局
- Disease Control Rate (DCR)(Up to approximately 58 months)
- Duration of Response (DOR)(Up to approximately 58 months)
- Progression-Free Survival (PFS)(Up to approximately 58 months)
- Overall Survival (OS)(Up to approximately 58 months)
- Area Under the Concentration-Time Curve Over the Dosing Interval t (AUCt) of Gocatamig(At designated time points (up to approximately 58 months))
- AUCt of I-DXd(At designated time points (up to approximately 58 months))
- AUCt of Deruxtecan (DXd)(At designated time points (up to approximately 58 months))
- AUCt of Anti-B7-H3 Antibody(At designated time points (up to approximately 58 months))
- Area Under the Steady-State Concentration-Time Curve Over the Dosing Interval t (AUCt,ss) of Gocatamig(At designated time points (up to approximately 58 months))
- AUCt,ss of I-DXd(At designated time points (up to approximately 58 months))
- AUCt,ss of DXd(At designated time points (up to approximately 58 months))
- AUCt,ss of Anti-B7-H3 Antibody(At designated time points (up to approximately 58 months))
- Maximum Concentration (Cmax) of Gocatamig(At designated time points (up to approximately 58 months))
- Cmax of I-DXd(At designated time points (up to approximately 58 months))
- Cmax of DXd(At designated time points (up to approximately 58 months))
- Cmax of Anti-B7-H3 Antibody(At designated time points (up to approximately 58 months))
- Trough Concentration (Ctrough) of Gocatamig(At designated time points (up to approximately 58 months))
- Ctrough of I-DXd(At designated time points (up to approximately 58 months))
- Ctrough of DXd(At designated time points (up to approximately 58 months))
- Ctrough of Anti-B7-H3 Antibody(At designated time points (up to approximately 58 months))
- Incidence of Anti-Drug Antibodies (ADAs) Against Gocatamig(At designated time points (up to approximately 58 months))
- Incidence of ADAs Against I-DXd(At designated time points (up to approximately 58 months))