試験ID jRCT2031250093
最終情報更新日：2025年5月21日
PD-L1 高発現腫瘍患者を対象に転移性非小細胞肺癌の一次治療におけるivonescimab とぺムブロリズマブを比較する無作為化二重盲検多地域共同第 3 相試験（HARMONi-7 試験）
基本情報
| 試験ID | jRCT2031250093 | |
|---|---|---|
| 研究名称 / Scientific Title（Acronym） | PD-L1 高発現腫瘍患者を対象に転移性非小細胞肺癌の一次治療におけるivonescimab とぺムブロリズマブを比較する無作為化二重盲検多地域共同第 3 相試験（HARMONi-7 試験） | A Randomized, Double-blinded, Multiregional Phase 3 Study of Ivonescimab Versus Pembrolizumab for the First-line Treatment of Metastatic Non-small Cell Lung Cancer in Patients Whose Tumors Demonstrate High PD-L1 Expression (HARMONi-7) |
| 平易な研究名称 / Public Title（Acronym） | A Randomized, Double-blinded, Multiregional Phase 3 Study of Ivonescimab Versus Pembrolizumab for the First-line Treatment of Metastatic Non-small Cell Lung Cancer in Patients Whose Tumors Demonstrate High PD-L1 Expression (HARMONi-7) | |
| 試験進捗状況/Recruitment status | 募集前 | Pending |
| 登録日時 | 2025年5月9日 | |
| 最終情報更新日 | 2025年5月21日 | |
| 試験開始日（予定日） | ||
| 試験終了日（予定日） | ||
| 組入れ開始日 / Date of first enrollment | ||
| 他の臨床研究登録機関発行の研究番号 | NCT06767514 | |
試験概要
| 試験実施地域 / Region | 日本 | USA,Japan,Canada,Japan,Mexico,Japan,China,Japan,Turkey,Japan,Serbia,Japan,France,Japan,Italy,Japan,Greece,Japan,Germany,Japan,Spain,Japan,Belgium,Japan,Romania,Japan,Hungary,Japan,Portugal,Japan,Poland,Japan |
|---|---|---|
| 実施都道府県 | 東京都 | |
| 目標症例数/Target sample size | 48 | |
| 対象疾患 / Health condition(s) or Problem(s) studied | 転移性非小細胞肺癌 | Metastatic non-small cell lung cancer |
| 試験のタイプ / Study type | 介入 | Interventional |
| 試験デザイン / Study design | ||
| ランダム化 / Randomization | ||
| 介入1 | 1：1の比で以下の2つの治療群に無作為に割り付ける。 ・A群：Ivonescimab （20 mg/kg 、3週間ごと）を60分（±10分）かけて静脈内投与する(最大24ヵ月)。体重が160 kg以上の患者にはivonescimabを3200 mgの固定用量で投与する。体重変更の場合を除き用量調節は認めない。 ・B群：ペムブロリズマブ（200 mg、3週間ごと）を60分（±10分）かけて静脈内投与する(最大24ヵ月)。減量は不可。 | |
| 介入2 | 1：1の比で以下の2つの治療群に無作為に割り付ける。 ・A群：Ivonescimab （20 mg/kg 、3週間ごと）を60分（±10分）かけて静脈内投与する(最大24ヵ月)。体重が160 kg以上の患者にはivonescimabを3200 mgの固定用量で投与する。10%を超える体重変更の場合を除き用量調節は認めない。 ・B群：ペムブロリズマブ（200 mg、3週間ごと）を60分（±10分）かけて静脈内投与する(最大24ヵ月)。減量は不可。 | |
| 主要評価項目 / Primary outcomes | ・OS ・RECIST第1.1版に基づいてIRRCが評価したPFS | -OS -PFS by IRRC, based on RECIST v1.1 |
| 副次評価項目 / Secondary outcomes | -ORR, DCR, and DoR assessed by IRRC based on RECIST v1.1 -Safety assessment: incidence and severity of AEs and clinically significant abnormal laboratory test results -PK characteristics: ivonescimab serum drug concentration profiles -Immunogenicity: number and percentage of patients with detectable ADA at baseline and post treatment | |
適格性
| 年齢（下限）/ Age minimum | 18歳以上 | >= 18age old |
|---|---|---|
| 年齢（上限）/ Age maximum | Not applicable | |
| 性別 / Gender | 男女両方 | Both |
| 選択基準 / Include criteria | 1. Voluntarily sign a written ICF 2. Age >= 18 years old at the time of enrollment 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 4. Expected life expectancy >= 3 months 5. Metastatic (Stage IV) NSCLC, according to American Joint Committee on Cancer (AJCC) 8th edition 6. Histologically or cytologically confirmed squamous or non-squamous NSCLC 7. Tumor demonstrates high PD-L1 expression based on an IHC pharmDx 22C3 (TPS >= 50%) or SP263 (TC >= 50%) IHC clinical assay approved/cleared by local health authorities and in a laboratory compliant with national provisions; this can be obtained from available results, or from archival or fresh tumor tissue for measurement of PD-L1 expression at a local or central laboratory. 8. At least one measurable noncerebral lesion according to RECIST v1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions since radiotherapy. 9. No prior systemic treatment for metastatic NSCLC. Patients receiving adjuvant or neoadjuvant chemotherapy or curative-intent chemoradiotherapy and/or PD-1/L1 inhibitors are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease. | |
| 除外基準 / Exclude criteria | Tumor-related features and treatment: 1. Histologic or cytopathologic evidence of the presence of small cell lung carcinoma. 2. Known actionable genomic alterations (EGFR, ALK, ROS1, and BRAF V600E) for which first-line approved therapies are indicated. For patients with non-squamous histology, actionable driver mutation testing results are required before randomization. 3. Has received any prior therapy for NSCLC in the metastatic setting Note: Local radiation therapy (plus/minus corticosteroids) for CNS or bone metastases is allowed. 4. Concurrent enrollment in another clinical study, unless patient is enrolled in a non-interventional clinical study or is completing survival follow-up. 5. Imaging during the screening period shows that the patient has: a. Radiologically documented evidence of major blood vessel invasion (central pulmonary artery, central pulmonary veins, aorta, brachiocephalic artery, common carotid artery, subclavian artery, superior vena cava) or tumor invading organs (heart, trachea, esophagus, central bronchi [not including segmental bronchi]) or if there is a risk of esophagotracheal or esophagopleural fistula in the opinion of the investigator. b. Radiographic evidence of major blood vessel encasement with narrowing of the vessel or intratumor lung cavitation or necrosis that the investigator determines will pose a significantly increased risk of bleeding. 6. Symptomatic CNS metastases, CNS metastases with hemorrhagic features, CNS metastasis >= 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease. Note: Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone =< 10 mg daily or equivalent). Past medical history and comorbidities: 7. Other prior malignancy (including previously treated NSCLC) unless the patient has undergone curative therapy with no evidence of recurrence of the disease for 3 years prior to randomization.The following malignancies will be allowed without the 3year interval after adequate treatment: basal cell or squamous cell carcinoma of skin, superficial bladder cancer, in situ cervical cancer, other in situ cancers, prostate cancer that does not need therapy, or other local tumors that are considered cured. 8. Active autoimmune or lung disease requiring systemic therapy (eg, with -disease modifying drugs, prednisone > 10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to randomization, however the following will be allowed: -Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted. -Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted. 9. History of major diseases before randomization, specifically: a. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] classification >= grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, moyamoya disease) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia) b. History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before randomization c. History of any grade arterial thromboembolic event, Grade 3 or above venous thromboembolic event as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to randomization d. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before randomization e. History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to randomization 10. Patients with > 30 Gy of chest radiation therapy within 6 months prior to randomization; non-thoracic radiation therapy > 30 Gy within 4 weeks prior to randomization, or palliative radiation therapy of =< 30 Gy within 7 days prior to randomization 11. Has pre-existing peripheral neuropathy that is >= Grade 2 by CTCAE version 5 |
責任研究者
| 責任研究者 / Name of lead principal investigator | Bai Vicky | |
|---|---|---|
| 組織名 / Organization | ||
| 部署名 / Division | Summit Therapeutics Sub, Inc. | |
| 住所 / Address | 2882 Sand Hill Road, Suite 106, Menlo Park, CA Japan 94025 | |
| 電話 / Telephone | 1-833-256-0522 | |
| 実施責任組織 / Affiliation | Vicky Bai | Tigerise Inc. |
| 研究費提供組織 / Funding Source | ||
| 共同実施組織 / Funding Source | ||
| 受付ID |
試験問い合わせ窓口
| 住所 / Address | 8F Kanda Miyuki Bldg., 1-chome-5-1 Kanda-Ogawamachi, Chiyoda-ku, Tokyo Tokyo Japan 101-0052 | |
|---|---|---|
| 電話 / Telephone | +81-3-5577-7835 | |
| ホームページURL | ||
| toru.tsunoda@tigerise.co.jp | ||
| 担当者 / Name of contact person | Toru Tsunoda |
倫理審査委員会
| 認定臨床研究審査委員会又は倫理審査委員会の名称 | ||
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| 上記委員会の認定番号 | 住所 / Address | |
| 電話番号 | ||
| 審査受付番号 | ||
| 当該臨床研究に対する審査結果 | ||
| 認定臨床研究審査委員会の承認日 | ||
変更・中止の場合
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| 中止年月日 | ||
| 中止の理由 | ||
終了の場合
| 終了届出日 | ||
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| 観察期間終了日 | ||
| 実施症例数 | ||
| 参加者の流れ（Participant flow） | ||
| 研究対象者の背景情報 | ||
| 疾病等の発生状況のまとめ | ||
| 主要評価項目及び副次評価項目のデータ解析及び結果 | ||
| 公開予定日 | ||
| 要約 | ||
| 研究実施計画書のURL | ||
| 結果に関する最初の出版物での発表日 | ||
| 結果と出版物に関するURL | ||
IPD data sharing
| 個々の研究対象者単位のデータ（IPD）を共有する計画 | ||
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| 計画の説明 | ||