Clinical Trial of HG146 Administered to Subjects With Advanced Solid Tumors or Lymphoma
A Phase I Open Label Study of HG146 Alone /in Combination With PD-(L)1 Inhibitor Administered With and Without Anticancer Agents in Participants With Advanced Solid Tumors or Lymphoma
This is a Phase I, open-label, repeat-dose, non-randomized, multicenter study to evaluate the safety, tolerability, and preliminary clinical activity and establish a recommended dose of HG146 administered orally (PO) alone (Part 1) or co-administered (Part 2) with PD-（L）1 inhibitor in subjects with refractory/relapsed solid tumors or Lymphoma. Part 1 consists of a dose escalation phae,Part2 consists of a dose escalation phase and a cohort expansion phase. In Part 1, escalating doses of HG146 will be evaluated as guided by the "3+3" approach. In Part 2A, escalating doses of HG146 in combination with PD-(L)1 inhibitor will be evaluated as guided by the "3+3" approach. In Part 2B, subjects will receive a single dose level of HG146 as identified based on data from Part 2, in combination with PD-(L)1 inhibitor . A total of approximately 96 subjects will be enrolled in this study, approximately 36 for dose escalation cohorts, and approximately 60 in the expansion cohorts.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Beijing、中国
- National Cancer Center/Cancer Hospital
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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
受講資格のある性別
説明
Key Inclusion Criteria:
1 Subject must be >=18 years of age at the time of signing the informed consent.
2- Ia/Ib dose escalation phase（Part1 and Part 2A）：Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.
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Ib dose expansion phase（Part 2）:
- Cohort 1,Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established, have not been treated with PD-(L)1 antibody； 2）Cohort 2,Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established, have progressed on PD-(L)1 antibody； 3 Measurable disease per RECIST version 1.1 or Lugano 2014（If applicable）. 4 Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1. 5 Has adequate organ function. 6 Signed informed consent form (ICF) and able to comply with study requirements.
Key Exclusion Criteria:
- Received prior therapies targeting HDAC.
- Symptomatic central nervous system (CNS) metastases that have required steroids within 4 weeks prior to first dose of study treatment.
- History of intolerant of anti-PD-(L)1 toxicity（Ib）.
- A condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of enrollment.
- Major surgery or major injury <=28 days before the first dose of study treatment,or anticipated major surgery during the study.
- Received other anticaner therapies within 4 weeks prior to first dose of study treatment or 5 half life period of anticancer drug .
- Active infection requiring systemic treatment.
- Prior allogeneic bone marrow transplantation or other solid organ transplantation ( Ib)
- Active autoimmune disease or disease of impaired immune system(Ib).
- History of Adrenal insufficiency.(Ib)
- History orConcurrent condition of other malignant tumors.
- Recent (within the past 6 months) history of Unstable or serious diseases, such as pancreatitis, severe angina, prolonged QT interval, congestive heart failure, myocardial infarction, pulmonary hypertension, stroke, and severe seizures, etc.
- History of severe lung disease.
- Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
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：順次割り当て
- 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:HG146 Monotherapy, Dose-escalation Cohort
Subjects will receive HG146 PO at every two days intervals (qod) for 14 consecutive days,7 days off, 21 days/ cycle. Escalating doses of HG146 will be evaluated using 3+3 approach. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
他の名前：
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実験的：Part 2A:HG146 + PD-(L)1 antibody, Dose escalation Cohort
Subjects will receive HG146 PO at every two days intervals (qod) for 14 consecutive days,7 days off, along with PD-(L)1 antibody IV once every 3 weeks (Q3W),21 days/ cycle. Escalating doses of HG146 in combination with PD-(L)1 antibody will be evaluated. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
他の名前：
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
他の名前：
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実験的：Part 2B-1：HG146 combination Expansion Cohort 1
Subjects who have not been treated with PD-(L)1 antibody，will receive HG146 po for 14 consecutive days,7 days off, in combination with PD-(L)1 antibody IV Q3W. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
他の名前：
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
他の名前：
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実験的：Part 2B-2：HG146 combination Expansion Cohort 2
Subjects who have progressed on PD-(L)1 antibody, will receive HG146 po for 14 consecutive days,7 days off, in combination with PD-(L)1 antibody IV Q3W. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
他の名前：
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
他の名前：
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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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Part I：Dose-Limiting Toxicities (DLTs)
時間枠：Up to 26 Days in Cycle 0 and Cycle 1
|
Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) |
Up to 26 Days in Cycle 0 and Cycle 1
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Part I：Serious Adverse Events (SAEs) and Adverse Events (AE)
時間枠：Up to 2 years
|
Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) According to Safety performance. |
Up to 2 years
|
|
Part I：Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146
時間枠：Up to 2 years
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Maximum tolerated dose or Recommended Phase II dose of HG146 will be decided according to safety and effective results. |
Up to 2 years
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Part 2A: Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)
時間枠：Up to 21 Days in Cycle 1
|
Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) |
Up to 21 Days in Cycle 1
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Part 2A: Serious Adverse Events (SAEs) and Adverse Events (AE)
時間枠：Up to 2 years
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Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) According to Safety performance. |
Up to 2 years
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Part 2A:Maximum tolerated dose or Recommended Phase II dose (RP2D) of HG146 in combination with PD-(L)1 antibody
時間枠：Up to 2 years
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Maximum tolerated dose or Recommended Phase II dose of HG146 will be decided according to safety and effective results. |
Up to 2 years
|
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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Part 1:Area under the concentration versus time curve (AUC) of HG146
時間枠：At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Part 1:Peak plasma concentration (Cmax) of HG146
時間枠：At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Part 1:Time of Cmax (Tmax) of HG146
時間枠：At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15(Except for cycle 0, each cycle is 21 days)
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Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15(Except for cycle 0, each cycle is 21 days)
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Part 1:Apparent terminal half-life (T1/2) of HG146
時間枠：At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
|
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Part1: objective response rate (ORR)
時間枠：Up to 2 years
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ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part1: Best overall response (BOR)
時間枠：Up to 2 years
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BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
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Part1: Duration of response (DOR)
時間枠：Up to 2 years
|
DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
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Part 1:Time-to-response (TTR)
時間枠：Up to 2 years
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TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
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Part 1:Progression-Free Survival (PFS)
時間枠：Up to 2 years
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PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
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Part 2:Area under the concentration versus time curve (AUC) of HG146
時間枠：At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
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Part 2:maximum observed plasma concentration (Cmax) of HG146
時間枠：At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
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Part 2:time of maximum observed plasma concentration (Tmax) of HG146
時間枠：At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
|
Part 2:apparent terminal half-life (T1/2) of HG146
時間枠：At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
|
Part2: objective response rate (ORR)
時間枠：Up to 2 years
|
ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
|
Part2: Best overall response (BOR)
時間枠：Up to 2 years
|
BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
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Part2: Duration of response (DOR)
時間枠：Up to 2 years
|
DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
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Part 2:Time-to-response (TTR)
時間枠：Up to 2 years
|
TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
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Part 2:Progression-Free Survival (PFS)
時間枠：Up to 2 years
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PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
|
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Overall survival (OS)
時間枠：Up to 2 years
|
OS will be assessed by the investigators |
Up to 2 years
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Yuankai Shi、National Cancer Center/Cancer Hospital
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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
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