Sikkerhet og foreløpig anti-tumoraktivitet av TYRA-430 i avansert hepatocellulært karsinom og andre faste svulster med aktivering av FGF/FGFR-traséavvik (SURF431)
Et multisenter, åpen, første-i-menneskelig studie av TYRA-430 i avansert hepatocellulært karsinom og andre faste svulster med aktivering av FGF/FGFR-veiavvik
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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Antatt)
Fase
- Fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: Lara Balick
- Telefonnummer: 929-792-5633
- E-post: TyraClinicalTrials@tyra.bio
Studiesteder
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Ontario
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Toronto, Ontario, Canada, M5G 2C4
- Rekruttering
- University Health Network Princess Margaret Cancer Center
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California
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Los Angeles, California, Forente stater, 90033
- Rekruttering
- USC Norris Comprehensive Cancer Center
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San Francisco, California, Forente stater, 94158
- Rekruttering
- UCSF Medical Center at Mount Zion
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Stanford, California, Forente stater, 94305
- Rekruttering
- Stanford Cancer Institute
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Kansas
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Westwood, Kansas, Forente stater, 66205
- Rekruttering
- The University of Kansas Medical Center
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Maryland
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Baltimore, Maryland, Forente stater, 21205
- Rekruttering
- John Hopkins University
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Massachusetts
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Boston, Massachusetts, Forente stater, 02114
- Rekruttering
- Mass General Cancer Center
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Michigan
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Detroit, Michigan, Forente stater, 48201
- Rekruttering
- Karmanos Cancer Institute
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New York
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New York, New York, Forente stater, 10043
- Rekruttering
- Columbia University Irving Medical Center
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Tennessee
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Nashville, Tennessee, Forente stater, 37203
- Tilbaketrukket
- Sarah Cannon Research Institute Oncology Partners
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Seoul, Sør -Korea
- Rekruttering
- Samsung Medical Center
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Seoul, Sør -Korea
- Rekruttering
- Seoul National University Hospital
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Seoul, Sør -Korea
- Rekruttering
- Asan Medical Center
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Seoul, Sør -Korea
- Rekruttering
- Severance Hospital, Yonsei University Health System
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Taipei, Taiwan
- Rekruttering
- Taipei Veterans General Hospital
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Taipei, Taiwan
- Rekruttering
- National Taiwan University Hospital
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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:
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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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Part A - Dose Escalation
Dose escalation of TYRA-430 as monotherapy at various dose levels. |
Oral TYRA-430 given daily. |
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Eksperimentell: 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. |
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Eksperimentell: 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. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Maximum tolerated dose (MTD)
Tidsramme: Up to 1 year
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MTD determination: dose limiting toxicity (DLT) rate in the first 28-day cycle |
Up to 1 year
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Rate and severity of adverse events of TYRA-430 as monotherapy
Tidsramme: First dose of study drug through 28 days after the last dose of study drug
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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
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Recommended Phase 2 dose(s) of TYRA-430
Tidsramme: Up to 2 years
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To determine recommended Phase 2 dose(s) of TYRA-430 |
Up to 2 years
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Cmax
Tidsramme: Opptil 2 år
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Opptil 2 år
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Tmax
Tidsramme: Opptil 2 år
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Opptil 2 år
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AUC0-last
Tidsramme: Opptil 2 år
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Opptil 2 år
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Auctau
Tidsramme: Opptil 2 år
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Opptil 2 år
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AUC0-∞
Tidsramme: Opptil 2 år
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Opptil 2 år
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Vd/f
Tidsramme: Opptil 2 år
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Opptil 2 år
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Cl/f
Tidsramme: Opptil 2 år
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Opptil 2 år
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T1/2
Tidsramme: Opptil 2 år
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Opptil 2 år
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Overall Response Rate (ORR)
Tidsramme: Up to 3.5 years
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The proportion of patients who experience a best response of confirmed CR or PR per RECIST 1.1 |
Up to 3.5 years
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Duration of Response (DOR)
Tidsramme: Up to 3.5 years
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Time from first investigator-assessed response to radiographic disease progression or death. |
Up to 3.5 years
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Disease Control Rate (DCR)
Tidsramme: Up to 3.5 years
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Best response of CR, PR, or SD per RECIST v1.1 > 12 months. |
Up to 3.5 years
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Time to Response (TTR)
Tidsramme: Up to 3.5 years
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The median time from the start of therapy to first response in confirmed responders. |
Up to 3.5 years
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studiestol: Doug Warner, MD, Tyra Biosciences, Inc
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Patologiske prosesser
- Neoplasmer etter nettsted
- Neoplasmer
- Neoplasmer etter histologisk type
- Neoplasmer i fordøyelsessystemet
- Sykdommer i fordøyelsessystemet
- Leversykdommer
- Neoplasmer, kjertel og epitel
- Adenokarsinom
- Neoplasmer i leveren
- Neoplastiske prosesser
- Karsinom
- Patologiske tilstander, tegn og symptomer
- Karsinom, hepatocellulært
- Neoplasma Metastase
Andre studie-ID-numre
- TYR430-101
Plan for individuelle deltakerdata (IPD)
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