試験ID jRCT2021220002
最終情報更新日：2026年5月10日
上皮成長因子受容体（EGFR）チロシンキナーゼ阻害剤（TKI）療法が奏効しなかった転移又は局所進行の上皮成長因子受容体変異陽性（EGFRm）非小細胞肺癌（NSCLC）を対象としてパトリツマブ デルクステカンとプラチナ製剤併用化学療法を比較する第III相無作為化非盲検試験(HERTHENA-Lung02)
基本情報
| 試験ID | jRCT2021220002 | |
|---|---|---|
| 研究名称 / Scientific Title（Acronym） | 上皮成長因子受容体（EGFR）チロシンキナーゼ阻害剤（TKI）療法が奏効しなかった転移又は局所進行の上皮成長因子受容体変異陽性（EGFRm）非小細胞肺癌（NSCLC）を対象としてパトリツマブ デルクステカンとプラチナ製剤併用化学療法を比較する第III相無作為化非盲検試験(HERTHENA-Lung02) | A Phase 3, Randomized, Open Label Study of Patritumab Deruxtecan Versus Platinum based Chemotherapy in Metastatic or Locally Advanced Epidermal Growth Factor Receptor-mutated (EGFRm) Non small Cell Lung Cancer (NSCLC) After Failure of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy (HERTHENA-Lung02) |
| 平易な研究名称 / Public Title（Acronym） | A Study of Patritumab Deruxtecan Versus Platinum-based Chemotherapy in Metastatic or Locally Advanced EGFRm NSCLC After Failure of EGFR TKI Therapy | |
| 試験進捗状況/Recruitment status | Not Recruiting | |
| 登録日時 | 2022年4月14日 | |
| 最終情報更新日 | 2026年5月10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 | NCT05338970 | |
試験概要
| 試験実施地域 / Region | 日本 | Australia,Japan,Austria,Japan,Belgium,Japan,China,Japan,France,Japan,German,Japan,Hong Kong,Japan,Italy,Japan,Netherlands,Japan,Poland,Japan,Portugal,Japan,Singapore,Japan,Korea,Japan,Spain,Japan,Switzerland,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan |
|---|---|---|
| 実施都道府県 | 宮城県 | |
| 目標症例数/Target sample size | 560 | |
| 対象疾患 / Health condition(s) or Problem(s) studied | 転移又は局所進行のEGFR活性化変異を有する非扁平上皮NSCLC | Metastatic or locally advanced nonsquamous NSCLC with an EGFR-activating mutation |
| 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 | 投与群1： ・ パトリツマブ デルクステカン 5.6 mg/kgを3週間に1回（q3W）投与 投与群2： ・ 4サイクルのプラチナ製剤併用化学療法：ペメトレキセド（500 mg/m2）＋シスプラチン（75 mg/m2）又はカルボプラチン（Calvert式による目標曲線下面積5［AUC5］）をq3W投与。4サイクルのプラチナ製剤＋ペメトレキセド併用療法後に病勢進行が認められなかった被験者は、サイクル数の制限なしのペメトレキセド維持投与に移行できる。 | |
| 介入2 | 投与群1： ・ パトリツマブ デルクステカン 5.6 mg/kgを3週間に1回（q3W）投与 投与群2： ・ 4サイクルのプラチナ製剤併用化学療法：ペメトレキセド（500 mg/m2）＋シスプラチン（75 mg/m2）又はカルボプラチン（Calvert式による目標曲線下面積5［AUC5］）をq3W投与。4サイクルのプラチナ製剤＋ペメトレキセド併用療法後に病勢進行が認められなかった被験者は、サイクル数の制限なしのペメトレキセド維持投与に移行できる。 | |
| 介入3 | 投与群1： ・ パトリツマブ デルクステカン 5.6 mg/kgを3週間に1回（q3W）投与 投与群2： ・ 4サイクルのプラチナ製剤併用化学療法：ペメトレキセド（500 mg/m2）＋シスプラチン（75 mg/m2）又はカルボプラチン（Calvert式による目標曲線下面積5［AUC5］）をq3W投与。4サイクルのプラチナ製剤＋ペメトレキセド併用療法後に病勢進行が認められなかった被験者は、サイクル数の制限なしのペメトレキセド維持投与に移行できる。 | |
| 主要評価項目 / Primary outcomes | RECIST v1.1に従ってBICRが評価するPFS PFSは、無作為割付された日から、客観的な病勢進行が最初に確認された日又は死亡（死因を問わない）日のうちいずれか早いほうまでの期間と定義する。 [評価期間: 投与開始日から約49ヵ月] | Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review Based on RECIST v1.1 Progression-free survival (PFS) is defined as the time from the date of randomization to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause. [Time Frame: Baseline up to approximately 49 months] |
| 副次評価項目 / Secondary outcomes | 1. 全生存期間 OS OSは、無作為割付された日から死亡（死因を問わない）日までの期間と定義する。 [評価期間: 投与開始日から約49ヵ月] 2. RECIST v1.1に従って治験責任医師又は治験分担医師が評価するPFS PFSは、無作為割付された日から、客観的な病勢進行が最初に確認された日又は死亡（死因を問わない）日のうちいずれか早いほうまでの期間と定義する。 [評価期間: 投与開始日から約49ヵ月] 3. 実施医療機関の標準的な診療方針で評価するPFS2 PFS2は、無作為割付された日から、新たな抗がん剤による最初の治療（実施されている場合）で進行が確認された日又は死亡（死因を問わない）日のうちいずれか早いほうまでの期間と定義する。 [評価期間: 投与開始日から約49ヵ月] 4. RECIST v1.1に従ってBICR及び治験責任医師又は治験分担医師が評価するORR ORRは、BORが確定CR又は確定PRである被験者の割合と定義する [評価期間: 投与開始日から約49ヵ月] 5. RECIST v1.1に従ってBICR及び治験責任医師又は治験分担医師が評価するDoR DoRは、客観的奏効（CR又はPR）が最初に確認された時点から、客観的進行が最初に確認された日又は死亡（死因を問わない）日のうちいずれか早いほうまでの期間と定義する。 [評価期間: 投与開始日から約49ヵ月] 6. RECIST v1.1に従ってBICR及び治験責任医師又は治験分担医師が評価するCBR CBRは、180日間以上継続して確定BORがCR、PR又はSDである被験者の割合と定義する [評価期間: 投与開始日から約49ヵ月] 7. RECIST v1.1に従ってBICR及び治験責任医師又は治験分担医師が評価するDCR DCRは、確定BORがCR、PR又はSDである被験者の割合と定義する。 [評価期間: 投与開始日から約49ヵ月] 8. RECIST v1.1に従ってBICR及び治験責任医師又は治験分担医師が評価するTTR TTRは、無作為割付された日から、後日確定される効果（CR又はPR）が最初に確認された日までの期間と定義する。 [評価期間: 投与開始日から約49ヵ月] 9. NSCLCにおける症状評価質問票（SAQ）のベースラインからの平均変化量 NSCLC-SAQは、NSCLC患者における疾患関連症状の変化を評価する。 [評価期間: 投与開始日から約49ヵ月] 10. Patient Global Impression of Change（PGI-C）のベースラインからの平均変化量 PGI-Cは、全般的な改善度の患者評価を7段階で記述する。 [評価期間: 投与開始日から約49ヵ月] 11. Patient Global Impression of Severity（PGI-S）のベースラインからの平均変化量 PGI-Sは、6つの回答オプションを含む単一の質問票である。 [評価期間: 投与開始日から約49ヵ月] 12. Patient Global Impression of Treatment Tolerability（PGI-TT）のベースラインからの平均変化量 PGI-TTによって、治療の忍容性について患者の全般的印象を把握する。 [評価期間: 投与開始日から約49ヵ月] 13. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30（EORTC-QLQ-C30）のベースラインからの平均変化量 EORTC-QLQ-C30によって、がん患者の生活の質（QoL）を評価する。 [評価期間: 投与開始日から約49ヵ月] 14. EuroQol Questionnaire-5 dimensions-5 levels（EQ-5D-5L）のベースラインからの平均変化量 EQ-5D-5Lは、医療技術評価に必要な全般的健康状態を測定するための標準化手法である。 [評価期間: 投与開始日から約49ヵ月] 15. 治験薬投与下で発現した有害事象（TEAE）が発現した被験者数 TEAEは、米国国立がん研究所の有害事象共通用語規準（NCI-CTCAE）第5.0版を用いて重症度分類が行われる。 [評価期間: 投与開始日から約49ヵ月] 16. 抗薬物抗体（ADA）陽性である被験者の割合（ベースライン時、ベースライン以後） パトリツマブ デルクステカンの免疫原性はADA評価によって確認される。 [評価期間: 投与開始日から約49ヵ月] 17. 治験薬投与下でADA発現が認められた被験者の割合 パトリツマブ デルクステカンの免疫原性はADA評価によって確認される。 [評価期間: 投与開始日から約49ヵ月] | 1. Overall Survival (OS) Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. [Time Frame: Baseline up to approximately 49 months] 2. Progression-free Survival (PFS) as Assessed by Investigator Review Based on RECIST v1.1 Progression-free survival (PFS) is defined as the time from the date of randomization to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause. [Time Frame: Baseline up to approximately 49 months] 3. Progression-free Survival on the next line of therapy (PFS2) as Assessed by Local Standard Clinical Practice Progression-free survival on the next line of therapy (PFS2)by local standard clinical practice is defined as the time from date of randomization to the documented progression on the first new anticancer therapy (if administered) or death due to any cause, whichever occurred first. [Time Frame: Baseline up to approximately 49 months] 4. Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1 Objective response rate (ORR) is defined as the proportion of participants who have a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). [Time Frame: Baseline up to approximately 49 months] 5. Duration of Response (DoR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1 Duration of response (DoR) is defined as the time from the first documentation of objective response (CR or PR) to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause. [Time Frame: Baseline up to approximately 49 months] 6. Clinical Benefit Rate (CBR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1 Clinical benefit rate (CBR) will be assessed by blinded independent central review and Investigator based on RECIST v1.1. CBR is defined as the proportion of participants who have a confirmed BOR of CR, PR, or stable disease (SD) that lasts for at least 180 days. [Time Frame: Baseline up to approximately 49 months] 7. Disease Control Rate (DCR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1 Disease control rate (DCR) is defined as the proportion of participants who have a confirmed BOR of CR, PR, or SD. [Time Frame: Baseline up to approximately 49 months] 8. Time to Response (TTR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1 Time to response (TTR) is defined as the time from the date of randomization to the date of the first documentation of response (CR or PR) that is subsequently confirmed. [Time Frame: Baseline up to approximately 49 months] 9. Mean Change from Baseline in Non-small Cell Lung Cancer - Symptom Assessment Questionnaire The NSCLC-SAQ will assess disease-related symptom change in patients with NSCLC. [Time Frame: Baseline up to approximately 49 months] 10. Mean Change from Baseline in Patient's Global Impression of Change The PGI-C is a 7-point scale depicting a participant's rating of overall improvement. [Time Frame: Baseline up to approximately 49 months] 11. Mean Change from Baseline in Patient's Global Impression of Severity The PGI-S is a one-item questionnaire that contains six response options. [Time Frame: Baseline up to approximately 49 months] 12. Mean Change from Baseline in Patient's Global Impression of Treatment Tolerability The PGI-TT will capture the patient's overall impression of treatment tolerability. [Time Frame: Baseline up to approximately 49 months] 13. Mean Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) The EORTC-QLQ-C30 will assess the patient's overall quality of life (QoL). [Time Frame: Baseline up to approximately 49 months] 14. Mean Change from Baseline in EuroQol Questionnaire-5 dimensions-5 levels (EQ-5D-5L) The EQ-5D-5L is a standardized instrument that will be used for measuring generic health status required for health technology assessments. [Time Frame: Baseline up to approximately 49 months] 15. Number of Participants With Treatment-emergent Adverse Events Treatment-emergent adverse events (TEAEs) will be graded by using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. [Time Frame: Baseline up to approximately 49 months] 16. Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) The immunogenicity of patritumab deruxtecan will be confirmed by assessing the anti-drug antibodies. [Time Frame: Baseline up to approximately 49 months] 17. Percentage of Participants Who Have Treatment-emergent ADA The immunogenicity of patritumab deruxtecan will be confirmed by assessing the anti-drug antibodies. [Time Frame: Baseline up to approximately 49 months] |
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. Is a male or female subject aged >=18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old). 2. Has histologically or cytologically documented metastatic or locally advanced non-squamous NSCLC not amenable to curative surgery or radiation. 3. Has documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R at diagnosis or thereafter. 4. Received 1 or 2 prior line(s) of an approved EGFR TKI treatment in the metastatic or locally advanced setting, which must include a third - generation EGFR TKI. 5. May have received either neoadjuvant and/or adjuvant treatment if progression to metastatic or locally advanced disease occurred at least 12 months after the last dose of such therapy and subsequently experienced disease progression on or after third-generation EGFR TKI treatment administered in the metastatic or locally advanced setting. 6. Has not received any other prior systemic therapies in the metastatic or locally advanced setting (including chemotherapy, immunotherapy etc) (even if administered in combination with EGFR TKI). 7. Has documentation of radiographic disease progression while receiving or after receiving a third generation EGFR TKI for metastatic or locally advanced disease. 8. Has at least 1 measurable lesion as per RECIST v1.1 by Investigator assessment. 9. Is willing to have a tumor biopsy or provide recently obtained tumor tissue. 10. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening. 11. Has adequate bone marrow reserve and organ function based on local laboratory evaluation within 14 days prior to randomization: - Platelet count: >=100,000/mm^3 or >=100 x 10^9/L - Absolute neutrophil count: >=1500/mm^3 or >=1.5 x 10^9/L - Hemoglobin (Hgb): >=9.0 g/dL - Creatine clearance (CrCl): CrCl >=45 mL/min calculated by using the Cockcroft-Gault equation or measured CrCl - Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT): AST/ALT <=3 x Upper limit of normal (ULN) - Total bilirubin (TBL): TBL <=1.5 x ULN - Serum albumin: >=2.5 g/dL - Prothrombin time (PT) or Prothrombin time-International normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/ partial thromboplastin time (PTT): <=1.5 x ULN, except for participants receiving coumarin-derivative anticoagulants or other similar anticoagulant therapy who must have PT-INR within therapeutic range as deemed appropriate by the Investigator | |
| 除外基準 / Exclude criteria | 1. Has any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy, or squamous NSCLC histology 2. Has any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during Screening 3. Has clinically severe respiratory compromise (based on the Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to the following: - Any underlying pulmonary disorder, restrictive lung disease, or pleural effusion - Any autoimmune, connective tissue, or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of Screening - OR prior complete pneumonectomy 4. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to randomization 5. Has evidence of any leptomeningeal disease 6. Has evidence of clinically active spinal cord compression or brain metastases, defined as being symptomatic and untreated, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms 7. Any prior treatment with any agent including an antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I, human epidermal growth factor receptor 3 (HER3) antibody, and any systemic therapies (other than EGFR TKIs) in the metastatic/locally advanced setting, including chemotherapy or any other systemic therapy in combination with an EGFR TKI 8. Has history of other active malignancy within 3 years prior to randomization, except for adequately resected nonmelanoma skin cancer, adequately treated intraepithelial carcinoma of the cervix, and any other curatively treated in situ disease 9. Has uncontrolled or significant cardiovascular disease prior to randomization 10. Has active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of active viral infection within 28 days of randomization 11. Has a known human immunodeficiency virus (HIV) infection that is not well controlled 12. Has clinically significant corneal disease |
責任研究者
| 責任研究者 / Name of lead principal investigator | Akihiro Inoguchi | |
|---|---|---|
| 組織名 / Organization | ||
| 部署名 / Division | DAIICHI SANKYO Co.,Ltd. | |
| 住所 / Address | 1-2-58, Hiromachi, Shinagawa-ku, Tokyo Tokyo Japan 140-8710 | |
| 電話 / Telephone | +81-3-6225-1111 | |
| 実施責任組織 / Affiliation | 井ノ口 明裕 | DAIICHI SANKYO Co.,Ltd. |
| 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 | 1-2-58, Hiromachi, Shinagawa-ku, Tokyo Tokyo Japan 140-8710 | |
|---|---|---|
| 電話 / Telephone | +81-3-6225-1111 | |
| ホームページURL | ||
| dsclinicaltrial_jp@daiichisankyo.com | ||
| 担当者 / Name of contact person | Contact for Clinical Trial Information |
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 | ||
|---|---|---|
| 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
| 中止届出日 | ||
|---|---|---|
| 中止年月日 | ||
| 中止の理由 | ||
終了の場合
| 終了届出日 | ||
|---|---|---|
| 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 | ||
|---|---|---|
| 計画の説明 | ||