進行性肝細胞癌およびその他の固形腫瘍におけるTYRA-430の安全性と予備抗腫瘍活性FGF/FGFR経路異常を活性化する (SURF431)
進行性肝細胞癌およびその他の固形腫瘍におけるTYRA-430の多施設、オープンラベル、ヒューマンの初心者の研究FGF/FGFR経路異常を活性化する
A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA-430 in cancers with FGF/FGFR pathway aberrations, including locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors.
調査の概要
状態
条件
介入・治療
詳細な説明
This is an open-label, multi-center, first-in-human, Phase 1 global study of TYRA-430, a first-in-class, selective, reversible fibroblast growth factor receptor (FGFR) 4 and 3 inhibitor, in locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors that contain FGF/FGFR pathway aberrations.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Lara Balick
- 電話番号：929-792-5633
- メール：TyraClinicalTrials@tyra.bio
研究場所
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California
-
Los Angeles、California、アメリカ、90033
- 募集
- USC Norris Comprehensive Cancer Center
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San Francisco、California、アメリカ、94158
- 募集
- UCSF Medical Center at Mount Zion
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Stanford、California、アメリカ、94305
- 募集
- Stanford Cancer Institute
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Kansas
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Westwood、Kansas、アメリカ、66205
- 募集
- The University of Kansas Medical Center
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Maryland
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Baltimore、Maryland、アメリカ、21205
- 募集
- John Hopkins University
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Massachusetts
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Boston、Massachusetts、アメリカ、02114
- 募集
- Mass General Cancer Center
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Michigan
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Detroit、Michigan、アメリカ、48201
- 募集
- Karmanos Cancer Institute
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New York
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New York、New York、アメリカ、10043
- 募集
- Columbia University Irving Medical Center
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Tennessee
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Nashville、Tennessee、アメリカ、37203
- 引きこもった
- Sarah Cannon Research Institute Oncology Partners
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-
-
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Ontario
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Toronto、Ontario、カナダ、M5G 2C4
- 募集
- University Health Network Princess Margaret Cancer Center
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-
-
-
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Taipei、台湾
- 募集
- Taipei Veterans General Hospital
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Taipei、台湾
- 募集
- National Taiwan University Hospital
-
-
-
-
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Seoul、韓国
- 募集
- Samsung Medical Center
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Seoul、韓国
- 募集
- Seoul National University Hospital
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Seoul、韓国
- 募集
- Asan Medical Center
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Seoul、韓国
- 募集
- Severance Hospital, Yonsei University Health System
-
-
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:
All Patients:
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
- Adequate end organ function.
- Ability to swallow oral formulations.
- Ability to understand and willingness to sign the ICF.
Part A:
-
Histologically confirmed locally advanced unresectable/metastatic HCC or histologically confirmed advanced solid tumor with documented FGF/FGFR pathway alterations
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For participants with histologically confirmed locally advanced or metastatic HCC:
- Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.
- Child-Pugh Score class A
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Must have previously received SOC appropriate for their tumor type. Any number of prior therapies, including FGFR inhibitors, are permitted.
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Agree to provide archival tumor tissue, if available. If an archived specimen is not available, a biopsy is not required.
Part B, Cohort 1:
- Histologically confirmed locally advanced/metastatic HCC who have previously received standard of care.
- Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.
- Child-Pugh Score class A
- Availability of an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen for submission to sponsor-designated central laboratory for FGF19 IHC testing.
- At least 1 measurable lesion by RECIST v1.1.
Part B, Cohort 2:
- Histologically confirmed advanced solid tumor except FGFR3-altered urothelial carcinoma and primary central nervous system tumors who have previously received standard of care. Note: Participants with confirmed diagnosis of locally advanced or metastatic HCC are not eligible for Cohort 2.
- Must have an eligible activating gain-of-function alteration in the FGFR4 gene, or focal amplifications of FGF19
- Archival tumor tissue biopsy specimen , if available. If a tissue biopsy specimen is not available, a biopsy is not required.
- At least 1 measurable lesion by RECIST v1.1.
Key Exclusion Criteria:
All Patients:
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Have disease that is suitable for local therapy administered with curative intent.
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Have not recovered from reversible toxicity of prior anticancer therapy to < Grade 1 or baseline (except toxicities that are not clinically significant or not expected to resolve, including but not limited to, alopecia, fatigue, skin discoloration, or Grade 1 neuropathy).
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Have received the following anticancer therapy:
- Any immunotherapy or other antibody therapy within 28 days prior to the first dose of the study drug.
- A TKI < 5 days or 5X the terminal Phase elimination half-lives, whichever is longer, prior to the first dose of TYRA-430.
- Other systemic therapy not listed above < 14 days prior to the first dose of the study drug.
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Participant discontinued a prior anti-FGFR therapy due to significant toxicity
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Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management.
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History of or current uncontrolled cardiovascular disease.
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Active, symptomatic, or untreated brain metastases.
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Have a diagnosis of primary CNS malignancies.
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Gastrointestinal disorders that will affect oral administration or absorption of TYRA-430.
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Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.
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Any reason that, in the view of investigator, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant.
Part B, Cohort 1:
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- Prior treatment with pan-FGFR inhibitors or FGFR4-selective inhibitors.
Part B, Cohort 2:
- Histologically confirmed locally advanced/metastatic HCC.
- Histologically confirmed urothelial cancer.
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 |
|---|---|
|
実験的：Part A - Dose Escalation
Dose escalation of TYRA-430 as monotherapy at various dose levels. |
Oral TYRA-430 given daily. |
|
実験的：Part B - Cohort 1 Dose Expansion
Dose expansion group for TYRA-430 monotherapy in advanced HCC at a dose(s) determined in Part A. |
Oral TYRA-430 given daily. |
|
実験的：Part B - Cohort 2 Dose Expansion
Dose expansion group for TYRA-430 monotherapy in advanced solid tumors at a dose(s) determined in Part A. |
Oral TYRA-430 given daily. |
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 |
|---|---|---|
|
Maximum tolerated dose (MTD)
時間枠：Up to 1 year
|
MTD determination: dose limiting toxicity (DLT) rate in the first 28-day cycle |
Up to 1 year
|
|
Rate and severity of adverse events of TYRA-430 as monotherapy
時間枠：First dose of study drug through 28 days after the last dose of study drug
|
Number of participants with TEAEs as assessed by CTCAE, v5.0 |
First dose of study drug through 28 days after the last dose of study drug
|
|
Recommended Phase 2 dose(s) of TYRA-430
時間枠：Up to 2 years
|
To determine recommended Phase 2 dose(s) of TYRA-430 |
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 |
|---|---|---|
|
Cmax
時間枠：最大2年
|
最大2年
|
|
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Tmax
時間枠：最大2年
|
最大2年
|
|
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AUC0-LAST
時間枠：最大2年
|
最大2年
|
|
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Auctau
時間枠：最大2年
|
最大2年
|
|
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AUC0-∞
時間枠：最大2年
|
最大2年
|
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Vd/f
時間枠：最大2年
|
最大2年
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Cl/f
時間枠：最大2年
|
最大2年
|
|
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T1/2
時間枠：最大2年
|
最大2年
|
|
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Overall Response Rate (ORR)
時間枠：Up to 3.5 years
|
The proportion of patients who experience a best response of confirmed CR or PR per RECIST 1.1 |
Up to 3.5 years
|
|
Duration of Response (DOR)
時間枠：Up to 3.5 years
|
Time from first investigator-assessed response to radiographic disease progression or death. |
Up to 3.5 years
|
|
Disease Control Rate (DCR)
時間枠：Up to 3.5 years
|
Best response of CR, PR, or SD per RECIST v1.1 > 12 months. |
Up to 3.5 years
|
|
Time to Response (TTR)
時間枠：Up to 3.5 years
|
The median time from the start of therapy to first response in confirmed responders. |
Up to 3.5 years
|
協力者と研究者
スポンサー
捜査官
- スタディチェア：Doug Warner, MD、Tyra Biosciences, Inc
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
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- TYR430-101
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
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