計劃書編號DS6000-109
NCT Number(ClinicalTrials.gov Identfier)NCT06161025
試驗執行中
2024-02-12 - 2030-07-31
Phase II/III
召募中6
ICD-10C56.1
右側卵巢惡性腫瘤
ICD-10C56.2
左側卵巢惡性腫瘤
ICD-10C56.9
未明示側性卵巢惡性腫瘤
ICD-10Z51.12
來院接受抗腫瘤免疫療法
ICD-9183.0
卵巢惡性腫瘤
一項針對鉑抗藥性的高惡性卵巢癌、原發性腹膜癌或輸卵管癌受試者使用 CDH6 導向抗體藥物複合體 Raludotatug Deruxtecan (R-DXd) 之第 2/3 期、多中心、隨機分配試驗
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試驗申請者
台灣第一三共股份有限公司
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試驗委託 / 贊助單位名稱
台灣第一三共股份有限公司
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臨床試驗規模
多國多中心
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更新日期
2026/04/24
試驗主持人及試驗醫院
實際收案人數
0 召募中
實際收案人數
0 召募中
實際收案人數
0 召募中
適應症
卵巢及其他子宮附屬器官之惡性腫瘤
試驗目的
本試驗為一項全球性、多中心、隨機分配、開放標記的第 2/3 期試驗，針對患有鉑抗藥性的高惡性度卵巢癌、原發性腹膜癌或輸卵管癌，並且先前曾接受至少 1 線且不超過 3 線全身性抗癌療法的受試者使用試驗藥物R-DXd的安全性及療效。第 2 期部分的主要目的是確定 R-DXd 的最佳劑量；第3部分主要是確定R-DXd的療效。
藥品名稱
Raludotatug Deruxtecan (R-DXd)
主成份
Raludotatug Deruxtecan
劑型
lyophilized powder
劑量
100 mg/vial
評估指標
第2期：評估 R-DXd 各劑量水準下由盲性獨立中央審查 (BICR) 評定的客觀反應率 (ORR)。
第3期：評估與試驗主持人選用的 paclitaxel、PLD或 topotecan 相比，使用 R-DXd 治療時由 BICR 評定的 ORR、無惡化存活期(PFS)。
第3期：評估與試驗主持人選用的 paclitaxel、PLD或 topotecan 相比，使用 R-DXd 治療時由 BICR 評定的 ORR、無惡化存活期(PFS)。
主要納入條件
1. 在開始任何試驗特定的資格程序前，簽署受試者同意書並註明日期。
2. 簽署受試者同意書時年齡 ≥ 18歲或最低法定成年年齡（以較大者為準）。
3. 受試者患有經組織學或細胞學證明的高惡性度漿液性卵巢癌 (OVC)、高惡性度子宮內膜型 OVC、原發性腹膜癌或輸卵管癌。
4. 受試者必須有至少 1 處病灶、先前未曾接受放射照射、適合進行切片，並且必須同意提供治療前切片和治療中切片組織檢體（試驗第 3 期部分不需要治療中切片檢體）。
5. 先前曾接受至少 1 線但不超過 3 線全身性抗癌療法：
6. 患有鉑抗藥性疾病。
• 如果受試者僅曾接受 1 線鉑療法，則必須已接受至少 4 個週期的鉑、必須有非疾病惡化的最佳反應，然後在施用最後一劑鉑之日期後 ＞90 天且 ≤180 天之間發生惡化
• 如果受試者曾接受 2 或 3 線鉑療法，則必須已接受至少 2 個週期的鉑，並且在鉑治療期間或施用最後一劑鉑之日期後 180 天內發生惡化
7. 針對有紀錄證實乳癌基因突變（生殖細胞和/或體細胞）的受試者，須先前已接受 PARP 抑制劑，除非受試者不符合 PARP 抑制劑治療的資格。
8. 針對有紀錄證實高葉酸受體alpha表現的受試者，須先前已接受mirvetuximab soravtansine治療，除非受試者因預防措施/不耐受而不符合mirvetuximab soravtansine治療的資格，或該治療在當地未獲准或無法取得。
9. 根據試驗主持人評估，依照固體腫瘤反應評估標準第 1.1 版 (RECIST v1.1)，透過電腦斷層或磁振造影評估具有至少 1處可測量病灶。
10. 美國東岸癌症臨床研究合作組織體能狀態為 0 或 1。
11. 具有必要的當地實驗室基線資料（試驗藥物給藥開始前 7 天內）
12. 若受試者是具有生育能力的女性，她在第一劑試驗藥物前 72 小時的血清驗孕必須呈陰性，並且必須願意在收納時、治療期期間以及最後一劑試驗藥物後 7 個月內使用高度有效的生育控制措施。
13. 女性受試者從篩選開始、整個試驗治療期期間，直到最後一次施用試驗藥物後至少7個月，不得捐贈卵子，或為了自身用途而取出卵子。
14. 願意且能夠遵守排定的回診、藥物使用計畫、實驗室檢測、其他試驗程序及試驗限制。
15. 僅適用於第 3 期（B 部分）：受試者必須有資格接受試驗主持人選用之化學治療組中包含的其中一種治療，且先前不得為了 OVC 接受過該種治療。1. 患有透明細胞、黏液性或肉瘤性組織學型態；含任何組織學型態的混合型腫瘤；或低惡性/邊緣型 OVC。
2. 具有臨床活性的腦部轉移、脊髓壓迫或軟腦膜癌病，定義為未接受治療或有症狀，或需要類固醇或抗癲癇藥物療法以控制相關症狀。
3. 隨機分配前過去 6 個月內發生任何下列情況：腦血管意外、短暫性腦缺血發作或其他動脈血栓栓塞事件。
4. 無法控制的或重大心血管疾病
5. 有需要皮質類固醇治療的（非感染性）間質性肺病 (ILD)/肺炎的病史、目前患有 ILD/肺炎，或在篩選時無法透過影像排除的疑似 ILD/肺炎。
6. 同時發生的肺部疾病所引發的臨床嚴重肺部損害，包括但不限於任何潛在的肺部疾患（即在受納試驗的 3 個月內發生肺栓塞、嚴重氣喘、重度慢性阻塞性肺病 [Severe Chronic Obstructive Pulmonary Disease, COPD]、侷限性肺疾、肋膜積液等），以及任何自體免疫、結締組織或發炎性疾患合併潛在肺部侵犯（例如類風濕性關節炎、乾燥症候群、類肉瘤病等），或先前曾接受全肺切除術。
7. 長期類固醇治療（＞10 mg/天）
8. 在受納前 3 年內有上皮性 OVC、原發性腹膜癌或輸卵管癌以外的惡性腫瘤病史。
9. 先前的抗癌療法尚有未緩解的毒性，定義為未緩解至美國國家癌症研究所不良事件共同術語標準 (NCI-CTCAE) 第 5.0 版 ≤ 第 1 級或基線的毒性（掉髮以外）。
10. 先前暴露於其他 CDH6 標靶藥劑或由 exatecan 衍生物（一種第一型拓樸異構酶抑制劑）組成的 ADC（例如 trastuzumab deruxtecan 或 datopotamab deruxtecan）。
11. 對 R-DXd 的任何賦形劑有過敏症的病史，或任何對試驗藥物治療的已知禁忌症，包括對試驗藥物產生過敏。
12. 已知有人類免疫缺乏病毒 (HIV) 感染且未獲得良好控制。如果當地法規或人體試驗委員會/倫理委員會可接受，則必須在篩選期內對受試者進行 HIV 病毒量檢測。
13. 有任何嚴重或無法控制的全身性疾病（包括活動性出血傾向或活動性感染、藥物濫用）的證據或其他因素，其經試驗主持人判定會使受試者不適合參與試驗或者會損及對試驗計畫書的遵從性。
14. 患有活動性或無法控制的 B 型肝炎和/或 C 型肝炎感染。在篩選期期間，受試者必須接受 B 型肝炎（B 型肝炎表面抗原 [Hepatitis B Virus Surface Antigen, HBsAg] 和抗 B 型肝炎核心抗體 [Anti-hepatitis B Core Antigen, anti-HBc]）及 C 型肝炎（C 型肝炎病毒抗體 [Hepatitis C Virus Antibody, HCV Ab]）的檢測。您如果符合下列情況，則符合資格
15. 懷孕中，或正在哺餵母乳或打算在試驗期間懷孕的女性。
16. 具有會妨礙定期追蹤的心理、社會、家庭或地理因素。
17. 先前或發生中之具有臨床意義的疾病、醫療狀況、手術史、身體檢查發現或實驗室檢驗結果異常，其經試驗主持人認定其可能影響受試者的安全性、改變試驗藥物的吸收、分佈、代謝或排泄，或混淆試驗結果的評估。
18. 在第一次暴露於試驗介入前 30 天內，有活性減毒疫苗（傳訊 RNA [Messenger RNA, mRNA] 和複製缺陷型腺病毒疫苗不被視為減毒活性疫苗）的接種史。
19. 僅適用於第 3 期（B 部分）：如果您有任何對照組治療中之當地獲准藥品標示中所包含的禁忌症病史，則不符合資格。
2. 簽署受試者同意書時年齡 ≥ 18歲或最低法定成年年齡（以較大者為準）。
3. 受試者患有經組織學或細胞學證明的高惡性度漿液性卵巢癌 (OVC)、高惡性度子宮內膜型 OVC、原發性腹膜癌或輸卵管癌。
4. 受試者必須有至少 1 處病灶、先前未曾接受放射照射、適合進行切片，並且必須同意提供治療前切片和治療中切片組織檢體（試驗第 3 期部分不需要治療中切片檢體）。
5. 先前曾接受至少 1 線但不超過 3 線全身性抗癌療法：
6. 患有鉑抗藥性疾病。
• 如果受試者僅曾接受 1 線鉑療法，則必須已接受至少 4 個週期的鉑、必須有非疾病惡化的最佳反應，然後在施用最後一劑鉑之日期後 ＞90 天且 ≤180 天之間發生惡化
• 如果受試者曾接受 2 或 3 線鉑療法，則必須已接受至少 2 個週期的鉑，並且在鉑治療期間或施用最後一劑鉑之日期後 180 天內發生惡化
7. 針對有紀錄證實乳癌基因突變（生殖細胞和/或體細胞）的受試者，須先前已接受 PARP 抑制劑，除非受試者不符合 PARP 抑制劑治療的資格。
8. 針對有紀錄證實高葉酸受體alpha表現的受試者，須先前已接受mirvetuximab soravtansine治療，除非受試者因預防措施/不耐受而不符合mirvetuximab soravtansine治療的資格，或該治療在當地未獲准或無法取得。
9. 根據試驗主持人評估，依照固體腫瘤反應評估標準第 1.1 版 (RECIST v1.1)，透過電腦斷層或磁振造影評估具有至少 1處可測量病灶。
10. 美國東岸癌症臨床研究合作組織體能狀態為 0 或 1。
11. 具有必要的當地實驗室基線資料（試驗藥物給藥開始前 7 天內）
12. 若受試者是具有生育能力的女性，她在第一劑試驗藥物前 72 小時的血清驗孕必須呈陰性，並且必須願意在收納時、治療期期間以及最後一劑試驗藥物後 7 個月內使用高度有效的生育控制措施。
13. 女性受試者從篩選開始、整個試驗治療期期間，直到最後一次施用試驗藥物後至少7個月，不得捐贈卵子，或為了自身用途而取出卵子。
14. 願意且能夠遵守排定的回診、藥物使用計畫、實驗室檢測、其他試驗程序及試驗限制。
15. 僅適用於第 3 期（B 部分）：受試者必須有資格接受試驗主持人選用之化學治療組中包含的其中一種治療，且先前不得為了 OVC 接受過該種治療。1. 患有透明細胞、黏液性或肉瘤性組織學型態；含任何組織學型態的混合型腫瘤；或低惡性/邊緣型 OVC。
2. 具有臨床活性的腦部轉移、脊髓壓迫或軟腦膜癌病，定義為未接受治療或有症狀，或需要類固醇或抗癲癇藥物療法以控制相關症狀。
3. 隨機分配前過去 6 個月內發生任何下列情況：腦血管意外、短暫性腦缺血發作或其他動脈血栓栓塞事件。
4. 無法控制的或重大心血管疾病
5. 有需要皮質類固醇治療的（非感染性）間質性肺病 (ILD)/肺炎的病史、目前患有 ILD/肺炎，或在篩選時無法透過影像排除的疑似 ILD/肺炎。
6. 同時發生的肺部疾病所引發的臨床嚴重肺部損害，包括但不限於任何潛在的肺部疾患（即在受納試驗的 3 個月內發生肺栓塞、嚴重氣喘、重度慢性阻塞性肺病 [Severe Chronic Obstructive Pulmonary Disease, COPD]、侷限性肺疾、肋膜積液等），以及任何自體免疫、結締組織或發炎性疾患合併潛在肺部侵犯（例如類風濕性關節炎、乾燥症候群、類肉瘤病等），或先前曾接受全肺切除術。
7. 長期類固醇治療（＞10 mg/天）
8. 在受納前 3 年內有上皮性 OVC、原發性腹膜癌或輸卵管癌以外的惡性腫瘤病史。
9. 先前的抗癌療法尚有未緩解的毒性，定義為未緩解至美國國家癌症研究所不良事件共同術語標準 (NCI-CTCAE) 第 5.0 版 ≤ 第 1 級或基線的毒性（掉髮以外）。
10. 先前暴露於其他 CDH6 標靶藥劑或由 exatecan 衍生物（一種第一型拓樸異構酶抑制劑）組成的 ADC（例如 trastuzumab deruxtecan 或 datopotamab deruxtecan）。
11. 對 R-DXd 的任何賦形劑有過敏症的病史，或任何對試驗藥物治療的已知禁忌症，包括對試驗藥物產生過敏。
12. 已知有人類免疫缺乏病毒 (HIV) 感染且未獲得良好控制。如果當地法規或人體試驗委員會/倫理委員會可接受，則必須在篩選期內對受試者進行 HIV 病毒量檢測。
13. 有任何嚴重或無法控制的全身性疾病（包括活動性出血傾向或活動性感染、藥物濫用）的證據或其他因素，其經試驗主持人判定會使受試者不適合參與試驗或者會損及對試驗計畫書的遵從性。
14. 患有活動性或無法控制的 B 型肝炎和/或 C 型肝炎感染。在篩選期期間，受試者必須接受 B 型肝炎（B 型肝炎表面抗原 [Hepatitis B Virus Surface Antigen, HBsAg] 和抗 B 型肝炎核心抗體 [Anti-hepatitis B Core Antigen, anti-HBc]）及 C 型肝炎（C 型肝炎病毒抗體 [Hepatitis C Virus Antibody, HCV Ab]）的檢測。您如果符合下列情況，則符合資格
15. 懷孕中，或正在哺餵母乳或打算在試驗期間懷孕的女性。
16. 具有會妨礙定期追蹤的心理、社會、家庭或地理因素。
17. 先前或發生中之具有臨床意義的疾病、醫療狀況、手術史、身體檢查發現或實驗室檢驗結果異常，其經試驗主持人認定其可能影響受試者的安全性、改變試驗藥物的吸收、分佈、代謝或排泄，或混淆試驗結果的評估。
18. 在第一次暴露於試驗介入前 30 天內，有活性減毒疫苗（傳訊 RNA [Messenger RNA, mRNA] 和複製缺陷型腺病毒疫苗不被視為減毒活性疫苗）的接種史。
19. 僅適用於第 3 期（B 部分）：如果您有任何對照組治療中之當地獲准藥品標示中所包含的禁忌症病史，則不符合資格。
主要排除條件
Exclusion Criteria
Has clear cell, mucinous, or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline OVC. (Note for Phase 3 [Part B]: seromucinous, low-grade serous carcinoma or ovarian sarcoma, carcinosarcoma and undifferentiated carcinoma are excluded.)
Inadequate washout period before Cycle 1 Day 1, defined as follows:
Major surgery <28 days
Radiation therapy <28 days (if palliative stereotactic radiation therapy without abdominal radiation, ≤14 days)
Systemic anticancer therapy (including antibody-drug therapy, retinoid therapy, and hormonal therapy) <28 days or 5 half-lives, whichever is shorter, before starting study drug
Chloroquine/hydroxychloroquine <14 days
Exposure to another investigational drug within 28 days prior to start of study treatment or current participation in other therapeutic investigational procedures
Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with untreated and asymptomatic brain metastases or subjects with treated brain metastases who are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy, at the investigator's discretion A minimum of 2 weeks must have elapsed between the end of radiotherapy and randomization and there should be no evidence of progression or need for steroid treatment or anticonvulsants for at least 2 weeks prior to randomization. Note: If there is a history or suspicion of central nervous system. Note: If there is a history or suspicion of central nervous system metastasis, a CT scan of the head or MRI of the brain must be performed at baseline.
Any of the following within the past 6 months prior to randomization: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
Uncontrolled or significant cardiovascular disease, including the following:
QT interval corrected with Fridericia's formula interval >470 ms.
Diagnosed or suspected long QT syndrome.
History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
The participant has bradycardia of less than 50 bpm, unless the subject has a pacemaker.
History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
Myocardial infarction within 6 months prior to screening.
Uncontrolled angina pectoris within 6 months prior to screening.
New York Heart Association Class 3 or 4 congestive heart failure.
Left ventricular ejection fraction <50% or institutional lower limit of normal as measured by echocardiography or multigated acquisition (MUGA) scan.
Coronary/peripheral artery bypass graft within 6 months prior to screening
Uncontrolled hypertension (HgCTCAE Grade ≥3 hypertension as per NCI-CTCAE version 5.0).
Complete left or right bundle branch block.
Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc), or prior pneumonectomy.
Chronic steroid treatment (>10 mg/day), with the exception of the following:
Inhaled steroids for asthma or COPD
Mineralocorticoids (eg, fludrocortisone) for subjects with orthostatic hypotension
Topical steroids for mild skin conditions
Low-dose supplemental corticosteroids for adrenocortical insufficiency
Premedication for treatment groups and/or premedication in case of any hypersensitivity
Intra-articular steroid injections
History of malignancy other than epithelial OVC, primary peritoneal cancer, or fallopian tube cancer within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (eg, 5-year OS rate >90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, ductal carcinoma in situ, or Stage 1 uterine cancer).
Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE Version 5.0, Grade ≤1 or baseline. Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade >2 for 3 months prior to randomization and managed with SOC treatment) that the investigator deems related to previous anticancer therapy, following discussion with the Sponsor, such as the following:
Chemotherapy-induced neuropathy
Fatigue
Endocrinopathies, which may include hypothyroidism, hyperthyroidism, Type 1 diabetes, hyperglycemia, and adrenal insufficiency
Skin pigmentation (vitiligo)
For Phase 2 (Part A): Prior exposure to other CDH6-targeted agents or an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan or datopotamab deruxtecan). For Phase 3 (Part B): Prior exposure to other CDH6-targeted agents or an antibody-drug conjugate containing a topoisomerase I inhibitor.
History of hypersensitivity to any excipients in the R-DXd or any known contraindication to treatment with, including hypersensitivity to, the study drug(s).
Has an active or uncontrolled human immunodeficiency virus (HIV) infection.
Has any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses or active infection, substance abuse) or other factors that, in the investigator's opinion, makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
Has an active or uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Hepatitis B and Hepatitis C Screening tests are required.
Subjects are eligible if:
Hepatitis B virus 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.
History of hepatitis C infection: eligible if the HCV viral load is below the level of detection in the absence of antiviral therapy during the previous 4 weeks.
Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT <3 × ULN, which are not attributable to HCV infection.
Female who is pregnant or breastfeeding or intends to become pregnant during the study.
Psychological, social, familial, or geographical factors that would prevent regular follow-up.
Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results.
Has a history of receiving live-attenuated vaccine (messenger RNA [mRNA] and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention.
For Phase 3 (Part B) only: Has clinical symptoms or radiographic evidence of intestinal obstruction.
For Phase 3 (Part B) only: Has ascites or pleural effusions that require repeated drainage (less than 4 weeks between drainages).
Has clear cell, mucinous, or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline OVC. (Note for Phase 3 [Part B]: seromucinous, low-grade serous carcinoma or ovarian sarcoma, carcinosarcoma and undifferentiated carcinoma are excluded.)
Inadequate washout period before Cycle 1 Day 1, defined as follows:
Major surgery <28 days
Radiation therapy <28 days (if palliative stereotactic radiation therapy without abdominal radiation, ≤14 days)
Systemic anticancer therapy (including antibody-drug therapy, retinoid therapy, and hormonal therapy) <28 days or 5 half-lives, whichever is shorter, before starting study drug
Chloroquine/hydroxychloroquine <14 days
Exposure to another investigational drug within 28 days prior to start of study treatment or current participation in other therapeutic investigational procedures
Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with untreated and asymptomatic brain metastases or subjects with treated brain metastases who are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy, at the investigator's discretion A minimum of 2 weeks must have elapsed between the end of radiotherapy and randomization and there should be no evidence of progression or need for steroid treatment or anticonvulsants for at least 2 weeks prior to randomization. Note: If there is a history or suspicion of central nervous system. Note: If there is a history or suspicion of central nervous system metastasis, a CT scan of the head or MRI of the brain must be performed at baseline.
Any of the following within the past 6 months prior to randomization: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
Uncontrolled or significant cardiovascular disease, including the following:
QT interval corrected with Fridericia's formula interval >470 ms.
Diagnosed or suspected long QT syndrome.
History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
The participant has bradycardia of less than 50 bpm, unless the subject has a pacemaker.
History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
Myocardial infarction within 6 months prior to screening.
Uncontrolled angina pectoris within 6 months prior to screening.
New York Heart Association Class 3 or 4 congestive heart failure.
Left ventricular ejection fraction <50% or institutional lower limit of normal as measured by echocardiography or multigated acquisition (MUGA) scan.
Coronary/peripheral artery bypass graft within 6 months prior to screening
Uncontrolled hypertension (HgCTCAE Grade ≥3 hypertension as per NCI-CTCAE version 5.0).
Complete left or right bundle branch block.
Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc), or prior pneumonectomy.
Chronic steroid treatment (>10 mg/day), with the exception of the following:
Inhaled steroids for asthma or COPD
Mineralocorticoids (eg, fludrocortisone) for subjects with orthostatic hypotension
Topical steroids for mild skin conditions
Low-dose supplemental corticosteroids for adrenocortical insufficiency
Premedication for treatment groups and/or premedication in case of any hypersensitivity
Intra-articular steroid injections
History of malignancy other than epithelial OVC, primary peritoneal cancer, or fallopian tube cancer within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (eg, 5-year OS rate >90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, ductal carcinoma in situ, or Stage 1 uterine cancer).
Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE Version 5.0, Grade ≤1 or baseline. Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade >2 for 3 months prior to randomization and managed with SOC treatment) that the investigator deems related to previous anticancer therapy, following discussion with the Sponsor, such as the following:
Chemotherapy-induced neuropathy
Fatigue
Endocrinopathies, which may include hypothyroidism, hyperthyroidism, Type 1 diabetes, hyperglycemia, and adrenal insufficiency
Skin pigmentation (vitiligo)
For Phase 2 (Part A): Prior exposure to other CDH6-targeted agents or an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan or datopotamab deruxtecan). For Phase 3 (Part B): Prior exposure to other CDH6-targeted agents or an antibody-drug conjugate containing a topoisomerase I inhibitor.
History of hypersensitivity to any excipients in the R-DXd or any known contraindication to treatment with, including hypersensitivity to, the study drug(s).
Has an active or uncontrolled human immunodeficiency virus (HIV) infection.
Has any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses or active infection, substance abuse) or other factors that, in the investigator's opinion, makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
Has an active or uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Hepatitis B and Hepatitis C Screening tests are required.
Subjects are eligible if:
Hepatitis B virus 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.
History of hepatitis C infection: eligible if the HCV viral load is below the level of detection in the absence of antiviral therapy during the previous 4 weeks.
Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT <3 × ULN, which are not attributable to HCV infection.
Female who is pregnant or breastfeeding or intends to become pregnant during the study.
Psychological, social, familial, or geographical factors that would prevent regular follow-up.
Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results.
Has a history of receiving live-attenuated vaccine (messenger RNA [mRNA] and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention.
For Phase 3 (Part B) only: Has clinical symptoms or radiographic evidence of intestinal obstruction.
For Phase 3 (Part B) only: Has ascites or pleural effusions that require repeated drainage (less than 4 weeks between drainages).
試驗計畫預計收納受試者人數
-
台灣人數
22 人
-
全球人數
860 人
