中国の早期NSCLCを対象としたニボルマブ単独療法またはナブパクリタキセルとカルボプラチンとの併用の二群（フェーズ2）探索研究
ニボルマブ (BMS-936558) は完全ヒト型の IgG4 (カッパ) アイソタイプ mAb で、活性化された免疫細胞上の PD-1 に結合し、受容体とそのリガンド PD-L1 (B7 H1/CD274) および PD-L2 (B7) の結合を妨害します。 -DC/CD273)、それによって阻害シグナルが無効になり、宿主の抗腫瘍応答が増強されます。 初期の臨床試験では、ニボルマブは黒色腫、腎細胞癌 (RCC)、非小細胞肺癌 (NSCLC) を含むいくつかの腫瘍タイプでの活性を実証しました。
ニボルマブは、NSCLC、RCC、黒色腫、頭頸部扁平上皮癌（SCCHN）およびその他の腫瘍（例、多形神経膠芽腫、中皮腫、小細胞肺癌、胃）の患者の治療のために臨床開発中である。
ニボルマブは、切除不能または転移性黒色腫、プラチナベースの化学療法中または後に進行した進行性NSCLC、抗血管新生療法で疾患が進行した進行性RCC、自家造血幹細胞移植および移植後のブレンツキシマブ ベドチン治療後に再発または進行した古典的ホジキンリンパ腫、およびプラチナベースの治療中または治療後に疾患が進行した再発または転移性の頭頸部扁平上皮癌。
提案された研究は、高リスク切除可能NSCLC患者におけるニボルマブの術前投与、またはネオアジュバント設定でのニボルマブとナブパクリタキセルおよびカルボプラチンの併用、および術後補助設定でのニボルマブ投与の有効性と安全性を評価し、ニボルマブの包括的な探索的特徴付けを促進することになる。これらの患者の腫瘍免疫微小環境と循環免疫細胞。 この研究で得られたデータは、NSCLCにおける抗PD-1および他の免疫療法の周術期および進行疾患の両方における前向き臨床試験を計画するための貴重な情報を提供します。 最終的には、最も利益が得られる可能性が高い NSCLC 患者が抗 PD-1 治療を受けられるようにし、逆に、NSCLC 患者に対する毒性や無効な治療のリスクを最小限に抑えるために、反応と毒性の将来性のあるバイオマーカーを発見することが非常に望ましいです。恩恵を受ける可能性は低い。
調査の概要
状態
条件
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究場所
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Guangdong
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Guangzhou、Guangdong、中国、510080
- Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
説明
包含基準:
- 初期段階のIB-IIIA、手術可能な非小細胞肺がん、組織内で確認
- 提案された肺手術に耐えられる肺機能容量
- 東部協力腫瘍学グループ (ECOG) のパフォーマンス ステータス 0-1
- 原発性肺腫瘍の利用可能な組織
除外基準:
- 局所進行性、手術不能または転移性疾患の存在
- 進行中の自己免疫疾患、既知の自己免疫疾患、または自己免疫疾患の疑いがある参加者
- T細胞の共刺激経路を標的とする薬剤（チェックポイント阻害剤など）による治療歴がある
他のプロトコルで定義された包含/除外基準が適用される可能性があります
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Part 1: Nivolumab Mono
In arm A, 24 participants will be enrolled into this arm according to PD-L1 expressing level (≥50%).Arm A consists of 3 cycles of neoadjuvant nivolumab (360mg every 3 weeks), and adjuvant nivolumab (360mg IV, every 3 weeks) up to 12 months
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Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks
Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy.
Segmentectomy and wedge resection are not permitted.
Within 6 weeks after definitive surgery, subjects in each cohort who are assessed to have benefited from neoadjuvant therapy (CR, PR, or SD) and have adequately recovered from surgery may receive adjuvant nivolumab (360 mg via IV infusion over at least 30 minutes, every 3 weeks) for up to 12 months, or until disease recurrence or unacceptable toxicity.
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実験的：Part 1: Nivolumab Plus Chemo
In arm B, up to 12 participants will be enrolled into each subgroup according to PD-L1 expressing level (<1% and 1%-49%).arm
B consists of 3 cycles of neoadjuvant nivolumab (360mg every 3 weeks) with nab-paclitaxel and carboplatin(nab-paclitaxel 135 mg/m2, d1, 8 and carboplatin AUC 5, d1 every three weeks ), and adjuvant nivolumab (360mg IV, every 3 weeks) up to 12 months
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AUC 5、3 週間ごとの d1
135 mg/m2、d1、8
Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks
Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy.
Segmentectomy and wedge resection are not permitted.
Within 6 weeks after definitive surgery, subjects in each cohort who are assessed to have benefited from neoadjuvant therapy (CR, PR, or SD) and have adequately recovered from surgery may receive adjuvant nivolumab (360 mg via IV infusion over at least 30 minutes, every 3 weeks) for up to 12 months, or until disease recurrence or unacceptable toxicity.
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実験的：Part:2: Exploratory cohort
In part 2，the treatment regimen consists of three cycles of neoadjuvant nivolumab (360 mg every 3 weeks) in combination with nab-paclitaxel and carboplatin (nab-paclitaxel 135 mg/m² on days 1 and 8, and carboplatin AUC 5 on day 1, every 3 weeks), followed by adjuvant nivolumab (360 mg every 3 weeks, administered via IV infusion over at least 30 minutes) for up to 12 months.
A total of 53 subjects will be enrolled in this study, regardless of PD-L1 expression.
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AUC 5、3 週間ごとの d1
135 mg/m2、d1、8
Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks
Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy.
Segmentectomy and wedge resection are not permitted.
Within 6 weeks after definitive surgery, subjects in each cohort who are assessed to have benefited from neoadjuvant therapy (CR, PR, or SD) and have adequately recovered from surgery may receive adjuvant nivolumab (360 mg via IV infusion over at least 30 minutes, every 3 weeks) for up to 12 months, or until disease recurrence or unacceptable toxicity.
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実験的：Part 3: Real-world cohort
Part 3 aims to evaluate the real-world effectiveness of neoadjuvant chemoimmunotherapy in patients with EGFR/ALK wild-type, potentially resectable or unresectable Stage III NSCLC. Treatment Paradigm: Eligible subjects will receive 3 cycles of neoadjuvant chemoimmunotherapy. Subsequently, a Multidisciplinary Team (MDT) will evaluate and determine the optimal definitive local therapy, triage patients to either radical resection or concurrent chemoradiotherapy (CCRT). Following the completion of local therapy, patients will receive adjuvant or consolidation immunotherapy for a duration of 1 year, administered every 3 weeks (Q3W). Sample Size: The planned enrollment for Part 3 is 215 patients. |
AUC 5、3 週間ごとの d1
135 mg/m2、d1、8
Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks
Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy.
Segmentectomy and wedge resection are not permitted.
Within 6 weeks after definitive surgery, subjects in each cohort who are assessed to have benefited from neoadjuvant therapy (CR, PR, or SD) and have adequately recovered from surgery may receive adjuvant nivolumab (360 mg via IV infusion over at least 30 minutes, every 3 weeks) for up to 12 months, or until disease recurrence or unacceptable toxicity.
In Part 3, for patients who are assessed by a Multidisciplinary Team (MDT) as unable to achieve R0 resection following neoadjuvant chemo-immunotherapy induction, the recommended radiotherapy regimen is: 60 Gy in 30 fractions (5 fractions per week) to 95% of the planning target volume (PTV).
Part 3: For patients who are determined by a Multidisciplinary Team (MDT) to be ineligible for R0 resection following neoadjuvant chemo-immunotherapy induction and require definitive radiotherapy, concurrent chemotherapy will be administered.
The regimen consists of cisplatin 30 mg/m² administered once weekly
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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MPR (Major Pathological Response) rate
時間枠：The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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As the primary outcome in part 1. MPR rate, defined as the number of participants with <10% residual tumor in lung and lymph nodes, divided by the number of treated participants for each arm.
Viable tumors in situ carcinoma should not be included in the MPR calculation.
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The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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EFS
時間枠：Since the last patient was enrolled for follow-up for 36 months
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Primary Outcome for Part 2. Outcome Measure Definition: Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: Disease progression that precludes surgical treatment; Local or distant recurrence; Death from any cause. Progression and recurrence will be assessed by the investigator according to RECIST 1.1. Subjects who die without documented disease progression or recurrence will be considered to have experienced an EFS event on the date of death. |
Since the last patient was enrolled for follow-up for 36 months
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18 months EFS rate
時間枠：The patient was followed up for 18 months after frist cycle neoajuvant treatment.
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Primary Outcome for Part 3. Outcome Measure Definition: 18months Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: Disease progression that precludes surgical treatment; Local or distant recurrence; Death from any cause. Progression and recurrence will be assessed by the investigator according to RECIST 1.1. Subjects who die without documented disease progression or recurrence will be considered to have experienced an EFS event on the date of death. |
The patient was followed up for 18 months after frist cycle neoajuvant treatment.
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Surgical Conversion Rate
時間枠：Perioperative/Periprocedural
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The primary endpoint of Part 3 is the surgical conversion rate, defined as the proportion of patients who successfully undergo definitive surgery following neoadjuvant chemoimmunotherapy, relative to the total enrolled population (Intent-to-Treat [ITT] analysis set). Statistical Analysis: The surgical conversion rate will be summarized descriptively using frequencies and percentages. The two-sided 95% exact confidence interval (CI) for the proportion will be calculated using the Clopper-Pearson method. |
Perioperative/Periprocedural
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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MPR (Major Pathological response) rate in 2 subgroups patients (PD-L1 <1%, and 1-49%) in Arm B
時間枠：The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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In part 1
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The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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Proportion of resection without delay
時間枠：The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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In part 1and 2
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The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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Number of Participants with Adverse Events
時間枠：During the treatment period, within at least 100 days after the cessation of neoadjuvant therapy, within 90 days after surgery, and within 30 days after adjuvant therapy.
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In parts 1 and 2 Safety and tolerability will be measured by incidence of AE, SAE, immune related AEs, deaths, and laboratory abnormalities
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During the treatment period, within at least 100 days after the cessation of neoadjuvant therapy, within 90 days after surgery, and within 30 days after adjuvant therapy.
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MRP rate
時間枠：The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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Also, as the primary outcome in part 1. MPR rate, defined as number participants with <10% residual tumor in lung and lymph nodes, divided by the number of treated participants for each arm Viable tumors in situ carcinoma should not be included in MPR calculation.
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The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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The EFS rates of all subjects with different PD-L1 expression statuses (PD-L1 < 1%, 1-49% and ≥ 50%)
時間枠：From date of enrollment up to the end of study, 5 years.
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In parts 1 and 2. Outcome Measure Definition: Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: Disease progression that precludes surgical treatment; Local or distant recurrence; Death from any cause. Progression and recurrence will be assessed by the investigator according to RECIST 1.1. Subjects who die without documented disease progression or recurrence will be considered to have experienced an EFS event on the date of death. |
From date of enrollment up to the end of study, 5 years.
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12 months EFS rate
時間枠：After 12 months of enrollment for all patientsAfter 12 months of enrollment for all patients
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In part 3, the 12-month EFS rate is the proportion of subjects who are alive and event-free at 12 months after the start of treatment.
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After 12 months of enrollment for all patientsAfter 12 months of enrollment for all patients
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OS
時間枠：From the date of enrollment until the date of death, assessed up to 100 months
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In part 3, OS is defined as the time from the start of treatment to death for any reason
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From the date of enrollment until the date of death, assessed up to 100 months
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TDDM (Time to Death or Distant Metastasis)
時間枠：From the date of the first dose of study treatment until the date of first documented distant metastasis or death from any cause, whichever occurs first, assessed up to approximately 60 months.
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In part 3, TDDM is defined as the start of the first treatment to distant metastasis, or death from any cause, whichever occurs first
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From the date of the first dose of study treatment until the date of first documented distant metastasis or death from any cause, whichever occurs first, assessed up to approximately 60 months.
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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pCR rate
時間枠：The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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The pCR (complete pathological response) rate is defined as the number of subjects with no residual tumor cells in the lungs and lymph nodes divided by the number of subjects receiving treatment.
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The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
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OS rate
時間枠：From date of enrollment up to the end of study, 5 years.
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OS is defined as the time since the treatment date and the death date, with the deletion date being the last known date when the subject was still alive
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From date of enrollment up to the end of study, 5 years.
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ORR
時間枠：Within 4 to 6 weeks after the patient completes the neoadjuvant treatment
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ORR is defined as the optimal objective tumor response rate between neoadjuvant therapy and surgery (according to RECIST 1.1 criteria).
All subjects will have their ORR calculated.
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Within 4 to 6 weeks after the patient completes the neoadjuvant treatment
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Safty
時間枠：From the time of enrollment until the completion of adjuvant therapy, which lasted for 13 weeks
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Descriptive statistical analysis of safety data was conducted based on the 4th edition of NCI CTCAE.
According to the most severe level determined by NCI CTCAE V4, all AE/ SAEs that occur after treatment and treatment-related AE/ SAEs will be summarized by systemic organ classification and standard terms.
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From the time of enrollment until the completion of adjuvant therapy, which lasted for 13 weeks
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18m-DFS rate
時間枠：The 18-month DFS rate refers to the probability of being event-free at 18 months calculated from the date of surgery.
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Disease-Free Survival (DFS) is defined as the time from the date of surgery to any of the following events: disease progression, recurrence, or death from any cause.
Disease progression and recurrence will be assessed according to RECIST 1.1 criteria.
For subjects who do not experience a DFS event, the date of censoring will be the date of the last evaluable tumor assessment after surgery.
For subjects who do not experience a DFS event but start subsequent anti-cancer therapy, the date of censoring will be the date of the last evaluable tumor assessment prior to receiving the subsequent anti-cancer therapy.
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The 18-month DFS rate refers to the probability of being event-free at 18 months calculated from the date of surgery.
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Landmark MRD positive rate
時間枠：One month after local therapy
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In part 3, the Landmark MRD positive rate is defined as the proportion of patients who were MRD positive at the Landmark time point among the total study population.
Furthermore, the comparison is made between the proportion of patients with MRD positivity among those who underwent surgery and the proportion of patients with MRD positivity among those who received radiotherapy.
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One month after local therapy
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協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CTONG 1804
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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