A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for the Treatment of Unresectable and/or Metastatic Solid Tumors Harboring HER2 Activating Mutations Regardless of Tumor Histology
概览
- 阶段
- 2 期
- 干预措施
- Trastuzumab deruxtecan
- 疾病 / 适应症
- Advanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,Breast
- 发起方
- AstraZeneca
- 入组人数
- 102
- 试验地点
- 30
- 主要终点
- Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR)
- 状态
- 进行中（未招募）
- 最后更新
- 上个月
概览
简要总结
This is an open-label, multi-center, single arm, Phase II study to evaluate the efficacy and safety of T-DXd for the treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology. The target population are patients who have progressed following prior treatment or who have no satisfactory alternative treatment options, including approved second line therapies in the specific tumor type. Pre-specified HER2 mutations will be locally assessed using NGS tests or alternative methods. Prior HER2 targeting therapy is permitted.
研究者
入排标准
入选标准
- •Adults ≥18 years old. Other age restrictions may apply as per local regulations.
- •Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772\_A775dup / A775\_G776insYVMA, L755S, G778\_P780dup / P780\_Y781insGSP, T862A, and V842I locally determined by NGS or a validated nucleic acid-based methodology (eg, qPCR, digital PCR) on tumor tissue, who have progressed following prior treatment or who have no satisfactory alternative treatment options.
- •Prior HER2 targeted therapy is permitted.
- •All patients must provide an FFPE tumor sample for retrospective central HER2 testing.
- •LVEF ≥50%
- •All patients have measurable target disease assessed by the Investigator based on RECIST v1.1
排除标准
- •HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma.
- •HER2 mutant NSCLC.
- •Medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic CHF, unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke.
- •History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening
- •Corrected QT interval by Fridericia's formula (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG.
- •Lung-specific intercurrent clinically significant severe illnesses.
- •History of active primary immunodeficiency, known HIV, active HBV or HCV infection
- •Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
- •Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
- •Has spinal cord compression or clinically active central nervous system metastases.
研究组 & 干预措施
T-DXd
T-DXd monotherapy
干预措施: Trastuzumab deruxtecan
结局指标
主要结局
Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR)
时间窗: Tumor scans performed at screening,then every 6 weeks (q6w) +/- 1 week relative to date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
Confirmed ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR), as determined by ICR per RECIST v1.1. A CR was defined as disappearance of all target lesions (TLs) and PR was defined as at least a 30% decrease in the sum of the diameters (dms) of TL, taking as reference the baseline sum of diameters as long as criteria for PD were not met. An ICR of all radiological imaging data was carried out using RECIST v1.1. All images were collected centrally. The imaging scans were reviewed by 2 independent radiologists and were adjudicated, if required.
次要结局
- PFS as Per RECIST v1.1 Using ICR and Investigator Assessment(Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months))
- Overall Survival (OS)(From the date of first treatment administration up to death, approximately 24 months)
- Percentage of Participants Alive at 6 and 12 Months(At Months 6 and 12)
- Serum Concentrations of Deruxtecan (MAAA-1181a)(Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days))
- Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment(Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months))
- Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment(At Months 6 and 12)
- Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment(Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months))
- Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment(Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months))
- Serum Concentrations of T-DXd and Total Anti-HER2 Antibody(Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days))
- Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd(Up to approximately 24 months)