2023-508056-19-00尚未招募3 期
DESTINY-Endometrial01: An Open-Label, Sponsor-Blinded, Randomized, Controlled, Multicenter, Phase III Study of Trastuzumab Deruxtecan (T-DXd) Plus Rilvegostomig or Pembrolizumab vs Chemotherapy Plus Pembrolizumab as First-Line Therapy of HER2-Expressing (IHC 3+/2+), Mismatch Repair Proficient (pMMR), Primary Advanced or Recurrent Endometrial Cancer
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 219
- 试验地点
- 81
- 主要终点
- Progression free survival (PFS) as assessed by BICR defined as time from randomization until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
研究概览
简要总结
To demonstrate the efficacy of first-line T-DXd + rilvegostomig (Arm A) and/or T-DXd+ pembrolizumab (Arm B) when compared to chemotherapy (carboplatin + paclitaxel) + pembrolizumab (Arm C), by assessment of progression free survival (PFS), as assessed by BICR, in participants with HER2-expressing (IHC 3+/2+), pMMR, primary advanced (Stage III/IV) or recurrent EC.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Participants must be ≥ 18 years of age at the time of screening. Other age restrictions may apply as per local regulations.
- •Adequate organ and bone marrow function within 14 days before randomization.
- •Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies are allowed except for sarcomas (carcinosarcomas are allowed).
- •Following surgery or diagnostic biopsy, participant must have primary advanced disease (Stage III/IV) or first recurrent endometrial cancer and meet at least one of the following criteria: - Primary Stage III (per FIGO 2023) disease with measurable disease at baseline per RECIST 1.1 based on the investigator’s assessment. - Primary Stage IV disease (per FIGO 2023) regardless of presence of measurable disease at baseline. - First recurrent disease regardless of presence of measurable disease at baseline.
- •Endometrial cancer with HER2 IHC expression of 3+ or 2+ as assessed by prospective central testing.
- •Endometrial cancer that is determined pMMR by prospective central IHC testing.
- •Provision of adequate FFPE tumor tissue sample of a tumor lesion that was not previously irradiated for central HER2, MMR, and PD-L1 IHC testing and valid central test results for randomization/ stratification.
- •Prior therapy: - Naïve to first-line systemic anticancer therapy. Participants may have received one prior line of adjuvant/neoadjuvant chemotherapy with curative intent (chemotherapy or chemoradiation) if disease recurrence or progression occurred ≥ 6 months after last dose of chemotherapy. Prior trastuzumab in the adjuvant/neoadjuvant setting is allowed. - No prior exposure to ADCs or immune checkpoint inhibitors including (but not limited to) anti-PD-1/PD-L1/PD-L2 and anti-CTLA-4 antibodies and therapeutic anticancer vaccines. - Participants may have received prior radiation therapy for the treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy. Adequate treatment washout period is required.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) 0-
- •Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before randomization.
排除标准
- •History of organ transplant.
- •Uncontrolled intercurrent illness, including, but not limited to ongoing or active known infection, serious chronic gastrointestinal conditions associated with diarrhea and active non-infectious skin disease requiring systemic treatment.
- •Spinal cord compression or clinically active central nervous system metastases.
- •Participants with a medical history of myocardial infarction (MI) within 6 months before randomization, or symptomatic congestive heart failure (CHF) (NYHA Class II to IV), clinically significant arrhythmia, or cardiomyopathy of any etiology. Participants with troponin levels above ULN at screening (as defined by the manufacturer), should have a cardiologic consultation before enrollment to rule out MI
- •History of (non-infectious) ILD/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- •Lung criteria: - Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.). - Any autoimmune, connective tissue or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of screening. - Prior pneumonectomy (complete).
- •Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
- •Active primary immunodeficiency/ active infectious disease(s) including: - Tuberculosis (TB) - HIV infection that is not well controlled. - Chronic or active hepatitis B, chronic or active hepatitis C; however, participants who have chronic hepatitis B and are receiving suppressive antiviral therapy are allowed to be enrolled if alanine aminotransferase (ALT) is normal and viral load is controlled.
- •Any concurrent anticancer treatment without an adequate washout period prior to the first dose of study intervention. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., HRT) is allowed.
结局指标
主要结局
Progression free survival (PFS) as assessed by BICR defined as time from randomization until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
Progression free survival (PFS) as assessed by BICR defined as time from randomization until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
次要结局
- Overall survival (OS) defined as the time from randomization until the date of death due to any cause.
- PFS as assessed by investigator (has the same attributes as estimand of PFS by BICR, except tumor assessment is by the investigator).
- PFS2 defined as the time from randomization to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.
- ORR as assessed by BICR is defined as the proportion of participants who have a complete response (CR) or partial response (PR), as determined and confirmed by BICR per RECIST 1.1. ORR as assessed and confirmed by the investigator has the same attributes as estimand of ORR by BICR except tumor assessment per the investigator.
- DoR as assessed by BICR will be defined as the time from the date of first documented response of confirmed responders until date of documented progression per RECIST 1.1 as assessed by BICR or death due to any cause. DoR as assessed by the investigator has the same attributes as estimand of DoR by BICR except tumor assessment per the investigator.
- Safety and tolerability (evaluated in terms of AEs/serious AEs (SAEs), AESI, vital signs, clinical safety laboratory assessments, ECG and ECHO/MUGA scan results).
- Serum concentration of T-DXd, total anti-HER2 antibody, DXd and rilvegostomig.
- Presence of ADAs for T-DXd and rilvegostomig.
- Patient-reported tolerability.
- Assessment of MMR and HER2 expression in tissue samples and their impact to clinical endpoints, addressing clinical utility of the tests.
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (81)
Loading locations...
相似试验
招募中
3 期
A trial to learn if Dato-DXd with rilvegostomig, or rilvegostomig alone, is safe and works compared with pembrolizumab in people who have advanced non-squamous non-small cell lung cancer (NSCLC) with high levels of the PD-L1 protein2023-505077-32-00AstraZeneca AB199
招募中
2 期
A Phase 2 Trial to Investigate Efficacy and Safety of Vipoglanstat in Women With EndometriosisEndometriosisNCT07260669Gesynta Pharma AB190
尚未招募
3 期
Study of Trastuzumab Deruxtecan with Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DO-01)Ovarian Cancer2024-516982-35-00Daiichi Sankyo Inc.182
招募中
3 期
A Study to Investigate Mocertatug Rezetecan Compared With Chemotherapy in Participants With Endometrial Cancer After Platinum-based Chemotherapy and Immunotherapy (BEHOLD-Endometrial01)NCT07286331GlaxoSmithKline600
招募中
2 期
Study of neoadjuvant patritumab deruxtecan with or without endocrine therapy in previously untreated patients – VALENTINE trial2023-503403-28-00Solti Group120