Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
2021年2月1日 更新者:Symphogen A/S
A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
This is the first study to test Sym022 in humans.
The primary purpose of this study is to see if Sym022 is safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.
調査の概要
詳細な説明
This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym022, an anti-lymphocyte activation gene 3 (anti-LAG-3) monoclonal antibody (mAb).
The goal is to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym022 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient cohorts with locally advanced/ unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.
If an MTD is not identified, a maximum administered dose (MAD) will be determined.
Sym022 will be given to patients in escalating dose cohorts; each patient will be given one fixed dose level.
研究の種類
介入
入学 (実際)
15
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.
- Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
- Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
- Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
- Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug.
Exclusion Criteria:
- Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a highly effective method of contraception.
- Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
- Hematologic malignancies other than lymphomas.
- Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable
- Active uncontrolled bleeding or a known bleeding diathesis
- Clinically significant cardiovascular disease or condition
- Significant pulmonary disease or condition
- Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
- An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
- History of organ transplantation (e.g. stem cell or solid organ transplant)
- History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy
- Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with exceptions.
- Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D1.
- Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Other Inhibitors of LAG-3
- Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to first administration of study drug and during study
- Any other investigational treatments within 4 weeks prior to and during study
- Radiotherapy for target lesions within 4 weeks prior to first administration of study drug unless PD has been documented in the lesion following treatment, and during study.
- Radiotherapy for non-target lesions within 1 week prior to first administration of study drug
- Immunosuppressive or systemic hormonal therapy
- Prophylactic use of hematopoietic growth factors within 1 week prior to first administration of study drug and during Cycle 1 of study
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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:なし
- 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 |
|---|---|
|
実験的:Sym022
Sym022 will be administered at up to 4 planned dose levels.
|
Sym022 は、LAG-3 に結合し、LAG-3/主要組織適合遺伝子複合体クラス II (MHC-II) の相互作用をブロックする組換え型の完全ヒト抗体であり、T 細胞の増殖とサイトカイン産生の増加を可能にします。
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 |
|---|---|---|
|
Assessment of Treatment Related Adverse Events (AEs).
時間枠:19 months
|
Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.
|
19 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Evaluation of the Immunogenicity of Sym022.
時間枠:19 months
|
Serum sampling and incidence (%) per dose level to assess the potential for anti-drug antibody (ADA) formation.
Count of participants show the number of participants who were tested positive for anti-Sym022 ADA.
|
19 months
|
|
Evaluation of Objective Response (OR) or Stable Disease (SD).
時間枠:13 months
|
Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017), or Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST), depending on tumor type.
The numbers shown below correspond to the values related to RECIST v1.1.
|
13 months
|
|
Time to Progression (TTP) of Disease.
時間枠:13 months
|
Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1, RECIL 2017, or iRECIST, depending on tumor type.
The numbers shown below correspond to the values related to RECIST v1.1.
|
13 months
|
|
Area Under the Concentration-time Curve in a Dosing Interval (AUC).
時間枠:19 months
|
Will be estimated using non-compartmental methods and actual timepoints.
|
19 months
|
|
Maximum Concentration (Cmax)
時間枠:0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
Will be derived from observed data.
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
|
Time to Reach Maximum Concentration (Tmax)
時間枠:0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
Will be derived from observed data.
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
|
Trough Concentration (Ctrough)
時間枠:0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
Will be derived from observed data.
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
|
Terminal Elimination Half-life (T½)
時間枠:0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
Will be estimated using non-compartmental methods and actual timepoints.
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
|
Clearance (CL)
時間枠:0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
Will be estimated using non-compartmental methods and actual timepoints.
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者:Lillian Siu, MD, FRCPC、Princess Margaret Cancer Centre
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2018年5月8日
一次修了 (実際)
2020年1月6日
研究の完了 (実際)
2020年1月6日
試験登録日
最初に提出
2018年3月26日
QC基準を満たした最初の提出物
2018年4月3日
最初の投稿 (実際)
2018年4月5日
学習記録の更新
投稿された最後の更新 (実際)
2021年2月18日
QC基準を満たした最後の更新が送信されました
2021年2月1日
最終確認日
2021年2月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
Sym022の臨床試験
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Symphogen A/S完了リンパ腫 | 固形腫瘍 | 転移性がんカナダ, アメリカ
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Symphogen A/S完了固形腫瘍 | 転移性がんアメリカ, カナダ, フランス, スペイン