A Phase 1b/2 Open-Label Clinical Study to Evaluate the Safety and Efficacy of MK-6070 and Ifinatamab Deruxtecan (I-DXd) in Participants With Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 327
- 试验地点
- 88
- 主要终点
- Number of Participants Who Experience an Adverse Event (AE)
研究概览
简要总结
Researchers are looking for new ways to treat people with extensive-stage small cell lung cancer (SCLC) that has relapsed or is refractory. Gocatamig is a new type of immunotherapy that uses a person's immune system to find and destroy cancer cells. Ifinatamab deruxtecan (also known as I-DXd) is a drug which binds to a specific target on cancer cells and delivers treatment to destroy those cells. Durvalumab is a different type of immunotherapy that also destroys cancer cells. Researchers want to know if giving gocatamig, I-DXd, and gocatamig with I-DXd or durvalumab can treat SCLC that did not respond or stopped responding to a prior treatment.
The goals of this study are to learn:
- If gocatamig alone, I-DXd alone, and gocatamig with I-DXd or durvalumab are safe and well tolerated
- If people who receive gocatamig alone, I-DXd alone, and gocatamig with I-DXd or durvalumab have their SCLC get smaller or go away
详细描述
This study will consist of two parts. Part 1 will assess the safety, tolerability, and efficacy of gocatamig and I-DXd at doses determined in study MK-6070-001 (NCT: NCT04471727). Part 2 will assess the safety and tolerability of gocatamig in participants in Japan and China. Part 3 will assess the safety, tolerability, and efficacy of gocatamig with durvalumab.
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
- •Has histologically or cytologically confirmed SCLC that is extensive stage (defined as Stage IV (T any, N any, M1a/b/c) following at least 1 prior line of systemic therapy that included platinum-based chemotherapy
- •Must be able to provide archival tumor tissue sample or fresh biopsy tissue sample
- •Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART)
排除标准
- •Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedure
- •Any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use except for a history of radiation pneumonitis that did not require steroids
- •Current history of ILD or clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
- •Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
- •Active or history of immune deficiency with the exception of HIV-infected participants with well controlled HIV on ART
- •History within 6 months before the first dose of study intervention 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) (New York Heart Association > class II), and/or uncontrolled cardiac arrhythmia
- •History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months before the first dose of study intervention
- •Active clinically significant infection requiring systemic therapy
- •History of allogeneic tissue/solid organ transplant
- •History of leptomeningeal disease
- •Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
- •Receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of chronic immunosuppressive therapy within 7 days prior to the first dose of study intervention
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Untreated or symptomatic brain metastases
- •Active viral hepatitis, defined as hepatitis A (hepatitis A virus immunoglobulin M [IgM] positive in the setting of associated signs/symptoms), hepatitis B (hepatitis B virus surface antigen [HbsAg] positive and/or detectable hepatitis B virus [HBV] deoxyribonucleic acid [DNA]), or hepatitis C (hepatitis C virus [HCV] antibody positive and detectable HCV ribonucleic acid). Participants with HBV with undetectable viral load after treatment are eligible. Participants with HCV with undetectable virus after treatment are eligible.
- •Part 1 only: Radiation therapy to the lung >30 Gy within 6 months before the start of study intervention
- •Part 1 only: Abdominal radiation within 4 weeks before start of study intervention
- •Part 1 only: Anticancer hormonal treatment (except luteinizing hormone-releasing hormone [LHRH]) within 2 weeks before start of study intervention
- •Part 1 only: Systemic anticancer therapy (except antibody-based anticancer therapy) or investigational agents within 3 weeks or 5 half-lives, whichever is longer
- •Part 1 only: Antibody-based cancer therapy within 3 weeks before start of study intervention
- •Part 1 only: Chloroquine/hydroxychloroquine within 2 weeks before start of study intervention
- •Part 1 only: Clinically significant corneal disease
- •Part 1 only: Has other uncontrolled or significant protocol-specified cardiovascular disease
研究组 & 干预措施
Part 1 Arm 1: Gocatamig and I-DXd
Participants will receive gocatamig and I-DXd at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Gocatamig (Biological)
Part 1 Arm 2: Gocatamig and I-DXd
Participants will receive gocatamig and I-DXd at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Gocatamig (Biological)
Part 1 Arm 2: Gocatamig and I-DXd
Participants will receive gocatamig and I-DXd at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Ifinatamab Deruxtecan (I-DXd) (Biological)
Part 1 Arm 3b: Gocatamig and I-DXd
Participants will receive gocatamig and I-DXd at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Gocatamig (Biological)
Part 1 Arm 3b: Gocatamig and I-DXd
Participants will receive gocatamig and I-DXd at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Ifinatamab Deruxtecan (I-DXd) (Biological)
Part 3 Arm 7: Gocatamig and Durvalumab
Participants will receive gocatamig and durvalumab at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Gocatamig (Biological)
Part 2 Arm 4: Gocatamig Monotherapy in Japan
Participants in Japan will receive escalating doses of gocatamig until documented disease progression or discontinuation criteria are met.
干预措施: Gocatamig (Biological)
Part 2 Arm 6: Gocatamig
Participants will receive gocatamig at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Gocatamig (Biological)
Part 2 Arm 5: Gocatamig Monotherapy in China
Participants in China will receive escalating doses of gocatamig until documented disease progression or discontinuation criteria are met.
干预措施: Gocatamig (Biological)
Part 3 Arm 7: Gocatamig and Durvalumab
Participants will receive gocatamig and durvalumab at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Durvalumab (Biological)
Part 1 Arm 1: Gocatamig and I-DXd
Participants will receive gocatamig and I-DXd at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Ifinatamab Deruxtecan (I-DXd) (Biological)
Part 1 Arm 3a: I-DXd Monotherapy
Participants will receive I-DXd until documented disease progression or discontinuation criteria are met.
干预措施: Ifinatamab Deruxtecan (I-DXd) (Biological)
Part 2 Arm 8: Gocatamig (Alternate Presentation)
Participants will receive an alternate presentation of gocatamig at a determined dose until documented disease progression or discontinuation criteria are met.
干预措施: Gocatamig (Biological)
结局指标
主要结局
Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 44 months
An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE in the study will be presented.
Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
时间窗: Up to approximately 3 weeks
A DLT is defined as any drug-related adverse event (AE) observed during the DLT evaluation period that meet pre-defined DTL criteria. Toxicities will be graded using National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) version 5.0, or the American Society for Transplant and Cellular Therapy (ASTCT) criteria. The number of participants who experience at least one DLT will be presented.
Number of Participants Who Discontinue Study Intervention Due to an AE
时间窗: Up to approximately 44 months
An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue the study intervention due to an AE in the study will be presented.
Part 1: Objective Response Rate (ORR)
时间窗: Up to approximately 44 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 the investigator will be presented.
次要结局
- Part 1, Part 2 (Arm 6), and Part 3 (Arm 7): Progression-Free Survival (PFS)(Up to approximately 44 months)
- Part 2 (Arm 5 and Arm 6) and Part 3 (Arm 7): ORR(Up to approximately 44 months)
- Maximum Concentration (Cmax) of gocatamig(At designated timepoints (up to approximately 44 months))
- Cmax of ifinatamab deruxtecan (I-DXd)(At designated timepoints (up to approximately 44 months))
- Cmax of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Cmax of Deruxtecan (DXd)(At designated timepoints (up to approximately 44 months))
- Cmax of Durvalumab(At designated timepoints (up to approximately 44 months))
- Time to maximum concentration (Tmax) of gocatamig(At designated timepoints (up to approximately 44 months))
- Tmax of I-DXd(At designated timepoints (up to approximately 44 months))
- Tmax of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Tmax of DXd(At designated timepoints (up to approximately 44 months))
- Area Under the Concentration-Time Curve Over the Dosing Interval t (AUCt) of gocatamig(At designated timepoints (up to approximately 44 months))
- AUCt of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- AUCt of I-DXd(At designated timepoints (up to approximately 44 months))
- AUCt of DXd(At designated timepoints (up to approximately 44 months))
- Terminal Half-Life (t1/2) of gocatamig(At designated timepoints (up to approximately 44 months))
- t1/2 of I-DXd(At designated timepoints (up to approximately 44 months))
- t1/2 of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- t1/2 of DXd(At designated timepoints (up to approximately 44 months))
- Steady State Maximum Concentration (Cmax,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- Cmax,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- Cmax,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Cmax,ss of DXd(At designated timepoints (up to approximately 44 months))
- Cmax,ss of Durvalumab(At designated timepoints (up to approximately 44 months))
- Steady State Ctrough (Ctrough,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- Ctrough,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- Ctrough,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Ctrough,ss of DXd(At designated timepoints (up to approximately 44 months))
- Ctrough,ss of Durvalumab(At designated timepoints (up to approximately 44 months))
- Steady State Time to Maximum Concentration (Tmax,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- Tmax,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- Tmax,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Tmax,ss of DXd(At designated timepoints (up to approximately 44 months))
- Area Under the Steady State Concentration-Time Curve Over Dosing Interval t (AUCt,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- AUCt,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- AUCt,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- AUCt,ss of DXd(At designated timepoints (up to approximately 44 months))
- Steady state t1/2 (t1/2,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- t1/2,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- t1/2,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- t1/2,ss of DXd(At designated timepoints (up to approximately 44 months))
- Accumulation Ratio (AC) of gocatamig(At designated timepoints (up to approximately 44 months))
- AC of I-DXd(At designated timepoints (up to approximately 44 months))
- AC of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- AC of DXd(At designated timepoints (up to approximately 44 months))
- Incidence of Anti-Drug Antibodies (ADAs) Against gocatamig(At designated timepoints (up to approximately 44 months))
- Incidence of ADAs Against I-DXd(At designated timepoints (up to approximately 44 months))
- Incidence of ADAs Against Durvalumab(At designated timepoints (up to approximately 44 months))
- Maximum Concentration (Cmax) of gocatamig(At designated timepoints (up to approximately 44 months))
- Cmax of ifinatamab deruxtecan (I-DXd)(At designated timepoints (up to approximately 44 months))
- Cmax of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Cmax of Deruxtecan (DXd)(At designated timepoints (up to approximately 44 months))
- Time to maximum concentration (Tmax) of gocatamig(At designated timepoints (up to approximately 44 months))
- Tmax of I-DXd(At designated timepoints (up to approximately 44 months))
- Tmax of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Tmax of DXd(At designated timepoints (up to approximately 44 months))
- Area Under the Concentration-Time Curve Over the Dosing Interval t (AUCt) of gocatamig(At designated timepoints (up to approximately 44 months))
- AUCt of I-DXd(At designated timepoints (up to approximately 44 months))
- AUCt of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- AUCt of DXd(At designated timepoints (up to approximately 44 months))
- Terminal Half-Life (t1/2) of gocatamig(At designated timepoints (up to approximately 44 months))
- t1/2 of I-DXd(At designated timepoints (up to approximately 44 months))
- t1/2 of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- t1/2 of DXd(At designated timepoints (up to approximately 44 months))
- Steady State Maximum Concentration (Cmax,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- Cmax,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- Cmax,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Cmax,ss of DXd(At designated timepoints (up to approximately 44 months))
- Steady State Ctrough (Ctrough,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- Ctrough,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- Ctrough,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Ctrough,ss of DXd(At designated timepoints (up to approximately 44 months))
- Steady State Time to Maximum Concentration (Tmax,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- Tmax,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- Tmax,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- Tmax,ss of DXd(At designated timepoints (up to approximately 44 months))
- Area Under the Steady State Concentration-Time Curve Over Dosing Interval t (AUCt,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- AUCt,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- AUCt,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- AUCt,ss of DXd(At designated timepoints (up to approximately 44 months))
- Steady state t1/2 (t1/2,ss) of gocatamig(At designated timepoints (up to approximately 44 months))
- t1/2,ss of I-DXd(At designated timepoints (up to approximately 44 months))
- t1/2,ss of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- t1/2,ss of DXd(At designated timepoints (up to approximately 44 months))
- Accumulation Ratio (AC) of gocatamig(At designated timepoints (up to approximately 44 months))
- AC of I-DXd(At designated timepoints (up to approximately 44 months))
- AC of Anti-B7-H3 Antibody(At designated timepoints (up to approximately 44 months))
- AC of DXd(At designated timepoints (up to approximately 44 months))
- Incidence of Anti-Drug Antibodies (ADAs) Against gocatamig(At designated timepoints (up to approximately 44 months))
- Cmax of Durvalumab(At designated timepoints (up to approximately 44 months))
- Cmax,ss of Durvalumab(At designated timepoints (up to approximately 44 months))
- Ctrough,ss of Durvalumab(At designated timepoints (up to approximately 44 months))
- Incidence of ADAs Against I-DXd(At designated timepoints (up to approximately 44 months))
- Part 1, Part 2 (Arm 5, Arm 6, and Arm 8), and Part 3 (Arm 7): Duration of Response (DOR)(Up to approximately 44 months)
- Part 1, Part 2 (Arm 6 and Arm 8), and Part 3 (Arm 7): Progression-Free Survival (PFS)(Up to approximately 44 months)
- Part 2 (Arm 5, Arm 6, and Arm 8) and Part 3 (Arm 7): ORR(Up to approximately 44 months)