FGF/FGFR 경로 수차 활성화 된 진행된 간세포 암종 및 기타 고형 종양에서 TYRA-430의 안전 및 예비 항 종양 활성 (SURF431)
FGF/FGFR 경로 수차를 활성화하는 고급 간세포 암종 및 기타 고형 종양에서 TYRA-430에 대한 다기관, 오픈 라벨, 최초의 인간 연구.
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.
연구 개요
상태
정황
개입 / 치료
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Lara Balick
- 전화번호: 929-792-5633
- 이메일: TyraClinicalTrials@tyra.bio
연구 장소
-
-
-
Taipei, 대만
- 모병
- Taipei Veterans General Hospital
-
Taipei, 대만
- 모병
- National Taiwan University Hospital
-
-
-
-
-
Seoul, 대한민국
- 모병
- Samsung Medical Center
-
Seoul, 대한민국
- 모병
- Seoul National University Hospital
-
Seoul, 대한민국
- 모병
- Asan Medical Center
-
Seoul, 대한민국
- 모병
- Severance Hospital, Yonsei University Health System
-
-
-
-
California
-
Los Angeles, California, 미국, 90033
- 모병
- USC Norris Comprehensive Cancer Center
-
San Francisco, California, 미국, 94158
- 모병
- UCSF Medical Center at Mount Zion
-
Stanford, California, 미국, 94305
- 모병
- Stanford Cancer Institute
-
-
Kansas
-
Westwood, Kansas, 미국, 66205
- 모병
- The University of Kansas Medical Center
-
-
Maryland
-
Baltimore, Maryland, 미국, 21205
- 모병
- John Hopkins University
-
-
Massachusetts
-
Boston, Massachusetts, 미국, 02114
- 모병
- Mass General Cancer Center
-
-
Michigan
-
Detroit, Michigan, 미국, 48201
- 모병
- Karmanos Cancer Institute
-
-
New York
-
New York, New York, 미국, 10043
- 모병
- Columbia University Irving Medical Center
-
-
Tennessee
-
Nashville, Tennessee, 미국, 37203
- 빼는
- Sarah Cannon Research Institute Oncology Partners
-
-
-
-
Ontario
-
Toronto, Ontario, 캐나다, M5G 2C4
- 모병
- University Health Network Princess Margaret Cancer Center
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
-
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
-
Must have previously received SOC appropriate for their tumor type. Any number of prior therapies, including FGFR inhibitors, are permitted.
-
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:
-
Have disease that is suitable for local therapy administered with curative intent.
-
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).
-
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.
-
Participant discontinued a prior anti-FGFR therapy due to significant toxicity
-
Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management.
-
History of or current uncontrolled cardiovascular disease.
-
Active, symptomatic, or untreated brain metastases.
-
Have a diagnosis of primary CNS malignancies.
-
Gastrointestinal disorders that will affect oral administration or absorption of TYRA-430.
-
Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.
-
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Part A - Dose Escalation
Dose escalation of TYRA-430 as monotherapy at various dose levels. |
Oral TYRA-430 given daily. |
|
실험적: 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. |
|
실험적: 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. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Maximum tolerated dose (MTD)
기간: 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
기간: 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
기간: Up to 2 years
|
To determine recommended Phase 2 dose(s) of TYRA-430 |
Up to 2 years
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Cmax
기간: 최대 2 년
|
최대 2 년
|
|
|
Tmax
기간: 최대 2 년
|
최대 2 년
|
|
|
Auc0-rast
기간: 최대 2 년
|
최대 2 년
|
|
|
Auctau
기간: 최대 2 년
|
최대 2 년
|
|
|
AUC0-∞
기간: 최대 2 년
|
최대 2 년
|
|
|
Vd/f
기간: 최대 2 년
|
최대 2 년
|
|
|
Cl/f
기간: 최대 2 년
|
최대 2 년
|
|
|
T1/2
기간: 최대 2 년
|
최대 2 년
|
|
|
Overall Response Rate (ORR)
기간: 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)
기간: 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)
기간: 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)
기간: Up to 3.5 years
|
The median time from the start of therapy to first response in confirmed responders. |
Up to 3.5 years
|
공동 작업자 및 조사자
수사관
- 연구 의자: Doug Warner, MD, Tyra Biosciences, Inc
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- TYR430-101
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .