A Randomized, Open-label, Phase 3 Study of MK-2870 vs Chemotherapy (Docetaxel or Pemetrexed) in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 556
- 试验地点
- 386
- 主要终点
- Progression-free Survival (PFS) of Participants with NSCLC with Epidermal Growth Factor Receptor (EGFR) Mutations
研究概览
简要总结
The purpose of this study is to evaluate sacituzumab tirumotecan versus chemotherapy (docetaxel or pemetrexed) for the treatment of previously-treated non-small cell lung cancer (NSCLC) with exon 19del or exon 21 L858R EGFR mutations (hereafter referred to as EGFR mutations or EGFR-mutated) or any of the follow genomic alterations: ALK gene rearrangements, ROS1 rearrangements, BRAF V600E mutations, NTRK gene fusions, MET exon 14 skipping mutations, RET rearrangements, or less common EGFR point mutations of exon 20 S768I, exon 21 L861Q, or exon 18 G719X mutations. The primary hypothesis is that sacituzumab tirumotecan is superior to chemotherapy with respect to overall survival (OS) in NSCLC with EGFR mutations.
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 and
排除标准
- •include but are not limited to the following:
- •Inclusion Criteria:
- •Histologically- or cytologically-documented advanced (Stage III not eligible for resection or curative radiation) or metastatic non-squamous NSCLC with specific mutations.
- •Documentation of locally assessed radiological disease progression while on or after last treatment based on Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.
- •Participants with genome mutations must have received 1 or 2 prior lines of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), including a third generation TKI for participants with a T790M mutation; and 1 platinum-based therapy after progression on or after EGFR TKI.
- •Measurable disease per RECIST 1.1 as assessed by the local site investigator.
- •Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
- •Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline.
- •Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
- •Have an ECOG performance status of 0 or 1 within 3 days before randomization.
- •Exclusion Criteria:
- •Has predominantly squamous cell histology NSCLC.
- •Has mixed tumor(s) with small cell elements.
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.
- •Has Grade ≥2 peripheral neuropathy.
- •Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
- •Has an EGFR T790M mutation and has not received a third generation EGFR TKI (eg, osimertinib).
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives (whichever is shorter) before randomization.
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- •Completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
- •Received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention.
- •Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC).
- •Received prior treatment with a topoisomerase I-containing ADC.
- •Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Active infection requiring systemic therapy.
- •History of noninfectious pneumonitis/ILD that required steroids or has current pneumonitis/ILD.
- •Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable, radiologically stable for at least 4 weeks and do not require glucocorticoids for at least 14 days prior to randomization.
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- •Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
研究组 & 干预措施
Chemotherapy
Participants will receive 75 mg/m^2 of docetaxel or 500 mg/m^2 of pemetrexed by IV infusion on Days 1 and 22 of every 6-week cycle.
干预措施: Docetaxel (Drug)
Chemotherapy
Participants will receive 75 mg/m^2 of docetaxel or 500 mg/m^2 of pemetrexed by IV infusion on Days 1 and 22 of every 6-week cycle.
干预措施: Pemetrexed (Drug)
Sacituzumab tirumotecan
Participants will receive 4 mg/kg of sacituzumab tirumotecan via intravenous (IV) infusion on Days 1, 15 and 29 of each 6-week cycle. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.
干预措施: Sacituzumab tirumotecan (Biological)
结局指标
主要结局
Progression-free Survival (PFS) of Participants with NSCLC with Epidermal Growth Factor Receptor (EGFR) Mutations
时间窗: Up to approximately 35 months
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.
Overall Survival (OS) of Participants with NSCLC with EGFR mutations
时间窗: Up to approximately 41 months
OS is defined as the time from randomization to death due to any cause.
次要结局
- OS of All Participants with NSCLC(Up to approximately 41 months)
- Objective Response Rate (ORR) of Participants with NSCLC with EGFR Mutations(Up to approximately 35 months)
- ORR of All Participants with NSCLC(Up to approximately 35 months)
- PFS of All Participants with NSCLC(Up to approximately 35 months)
- Duration of Response (DOR) of All Participants with NSCLC(Up to approximately 6 years)
- Change in Score from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)(Baseline and up to approximately 48 weeks)
- TTD from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31)(Up to approximately 48 weeks)
- Time to Deterioration from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40)(Up to approximately 48 weeks)
- Change in Score from Baseline in Global Health Status/QoL Score (European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Items 29 and 30)(Baseline and up to approximately 48 weeks)
- Change in Score from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31)(Baseline and up to approximately 48 weeks)
- Time to Deterioration (TTD) from Baseline in Global Health Status/QoL Score (EORTC QLQ-C30 Items 29 and 30)(Up to approximately 48 weeks)
- TTD from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)(Up to approximately 48 weeks)
- Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 6 years)
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)(Up to approximately 4 years)
- Change in Score from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40)(Baseline and up to approximately 48 weeks)