Dosiseskalering og udvidelse af BBO-10203 i avancerede solide tumorer (BREAKER-101)
En fase 1a/1b undersøgelse af PI3Kα:RAS Breaker BBO-10203 i forsøgspersoner med avancerede solide tumorer (BREAKER-101 undersøgelsen)
First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.
Studieoversigt
Status
Betingelser
- Metastatisk tyktarmskræft
- Avanceret brystkræft
- Metastatisk lungekræft
- Metastatisk brystkræft
- Solid tumor, voksen
- HER2-positiv metastatisk brystkræft
- HER2-positiv avanceret brystkræft
- HER2 mutationsrelaterede tumorer
- Avanceret lungekræft
- HR-positiv, HER2-negativ avanceret brystkræft
- KRAS mutant metastatisk kolorektal cancer
Intervention / Behandling
Detaljeret beskrivelse
This is an open-label, multi-center Phase 1a/1b study designed to evaluate the safety, tolerability, preliminary antitumor activity, and PK of BBO-10203 as a single agent and in combination with Trastuzumab, Fulvestrant +/- Ribociclib, or FOLFOX + Bevacizumab in patients with locally advanced unresectable or metastatic (ie, advanced) solid tumors. The study includes a dose escalation phase and an expansion phase.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: BBOT (BridgeBio Oncology Therapeutics)
- Telefonnummer: 650-405-8440
- E-mail: Breaker-101ct.gov@bridgebiooncology.com
Studiesteder
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New South Wales
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Randwick, New South Wales, Australien, 2031
- Rekruttering
- Scientia Clinical Research
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Victoria
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Melbourne, Victoria, Australien, 3000
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- Peter MacCallum Cancer Centre
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Rio Grande do Norte
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Natal, Rio Grande do Norte, Brasilien, 59062
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- Liga Contra o Câncer
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Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, Brasilien, 90470
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- FUTTURA Oncologia
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Porto Alegre, Rio Grande do Sul, Brasilien, 90610
- Rekruttering
- Hospital São Lucas da PUCRS
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São Paulo
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Sorocaba, São Paulo, Brasilien, 18056
- Rekruttering
- IEPE - Unimed Sorocaba
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São Paulo, São Paulo, Brasilien, 01246
- Rekruttering
- Instituto do Câncer do Estado de São Paulo - ICESP
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São Paulo, São Paulo, Brasilien, 01317
- Rekruttering
- Clinica de Pesquisas e Centro de Estudos Em Oncologia Ginecologica e Mamaria Ltda
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California
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Duarte, California, Forenede Stater, 91010
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- City of Hope Comprehensive Cancer Center
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Los Angeles, California, Forenede Stater, 90095
- Rekruttering
- University of California Los Angeles
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San Diego, California, Forenede Stater, 92093
- Rekruttering
- University of California San Diego Moores Cancer Center
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San Francisco, California, Forenede Stater, 94158
- Trukket tilbage
- UCSF Helen Diller Family Comprehensive Cancer Center
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Florida
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Tampa, Florida, Forenede Stater, 33612
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- Moffitt Cancer Center
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46202
- Rekruttering
- Indiana University Simon Comprehensive Cancer Center
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- Rekruttering
- Massachusetts General Hospital
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Boston, Massachusetts, Forenede Stater, 02215
- Rekruttering
- Dana-Farber Cancer Insitute
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Missouri
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Kansas City, Missouri, Forenede Stater, 64111
- Rekruttering
- St. Lukes Hospital of Kansas City
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St Louis, Missouri, Forenede Stater, 63110
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- Washington University School of Medicine
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New York
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New York, New York, Forenede Stater, 10065
- Rekruttering
- Memorial Sloan Kettering Cancer Center
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New York, New York, Forenede Stater, 10032
- Rekruttering
- Columbia University Irving Medical Center
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37203
- Rekruttering
- SCRI Oncology Partners
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Texas
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Dallas, Texas, Forenede Stater, 75390
- Rekruttering
- University of Texas Southwestern Medical Center
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Dallas, Texas, Forenede Stater, 75230
- Rekruttering
- SCRI at Mary Crowley
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Houston, Texas, Forenede Stater, 77030
- Rekruttering
- The University of Texas MD Anderson Cancer Center
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San Antonio, Texas, Forenede Stater, 78229
- Rekruttering
- University of Texas San Antonio (UTSA)
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Washington
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Seattle, Washington, Forenede Stater, 98109
- Rekruttering
- Fred Hutchinson Cancer Center
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Wisconsin
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Madison, Wisconsin, Forenede Stater, 53792
- Rekruttering
- Wisconsin Institute for Medical Research
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Bordeaux, Frankrig, 33000
- Rekruttering
- Institut Bergonie
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Lyon, Frankrig, 69008
- Rekruttering
- Centre Léon Bérard
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Occitanie
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Montpellier, Occitanie, Frankrig, 34298
- Rekruttering
- Institut régional du Cancer de Montpellier - Val d'Aurelle
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Paris
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Saint-Cloud, Paris, Frankrig, 92210
- Rekruttering
- Institut Curie - René-Huguenin Hospital
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Pays de la Loire Region
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Saint-Herblain, Pays de la Loire Region, Frankrig, 44805
- Rekruttering
- lnstitut de Cancérologie de l'Ouest - Site Saint-Herblain
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Île-de-France Region
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Villejuif, Île-de-France Region, Frankrig, 94805
- Rekruttering
- Institut Gustave Roussy
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Barcelona, Spanien, 08023
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- IOB Institute of Oncology - Hospital Quironsalud Barcelona
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Barcelona, Spanien, 08023
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- START Barcelona - HM Nou Delfos Hospital
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Lleida, Spanien, 25198
- Rekruttering
- Hospital Universitari Arnau de Vilanova
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Madrid, Spanien, 28041
- Rekruttering
- Hospital Universitario 12 de Octubre
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Madrid, Spanien, 28040
- Rekruttering
- Hospital Universitario Fundación Jiménez Díaz
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Valencia, Spanien, 46026
- Rekruttering
- Hospital Universitari i Politècnic La Fe
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Catalonia
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Barcelona, Catalonia, Spanien, 08035
- Rekruttering
- Hospital Universitario Vall d'Hebron
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Madrid
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Madrid, Madrid, Spanien, 28007
- Rekruttering
- Hospital Beata Maria Ana
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Pozuelo de Alarcón, Madrid, Spanien, 28223
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- Hospital Quiron Madrid - NEXT Oncology
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Seoul, Sydkorea, 03080
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- Seoul National University Hospital
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Seoul
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Seoul, Seoul, Sydkorea, 05505
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- Asan Medical Center (AMC)
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive/HER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC)
- Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only)
- Stable brain metastases
- Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC)
- Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy
- BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4/6i
- BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted
- BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required
Exclusion Criteria:
- Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR/MSI-H tumors
- Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1/BRAF/RET/MET/EGFR exon20 insertion/NTRK/HER2)
- Patients with untreated and/or non-stable brain metastases
Other inclusion/exclusion criteria are specified in the protocol
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: BBO-10203
Participants enrolled in this cohort will receive BBO-10203 tablets orally (different dose levels will be evaluated) once daily as monotherapy. This cohort will enroll patients with HER2-positive advanced breast cancer, HR-positive HER2-negative advanced breast cancer, advanced colorectal cancer, and advanced lung cancer. |
Participants will receive assigned dose of BBO-10203 orally once daily |
|
Eksperimentel: BBO-10203 + Trastuzumab
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with trastuzumab. This cohort will enroll patients with HER2-positive advanced breast cancer. |
Participants will receive assigned dose of BBO-10203 orally once daily Participants will receive trastuzumab as infusion or subcutaneous injection every 21 days |
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Eksperimentel: BBO-10203 + Fulvestrant
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer. |
Participants will receive assigned dose of BBO-10203 orally once daily Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15) Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off) |
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Eksperimentel: BBO10203 + Fulvestrant + Ribociclib
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with fulvestrant and ribociclib as determined in the dose escalation. This cohort will enroll patients with HR-positive, HER2-negative advanced breast cancer. |
Participants will receive assigned dose of BBO-10203 orally once daily Patients will receive Fulvestrant as an intramuscular injection every 28 days (additional dose on C1D15) Patients will receive Ribociclib orally once a day (21 days on treatment, 7 days off) |
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Eksperimentel: BBO10203 + FOLFOX + Bevacizumab
Participants enrolled in this cohort will receive BBO-10203 tablets orally in combination with FOLFOX and bevacizumab. This cohort will enroll patients with KRAS-mutant advanced colorectal cancer. |
Participants will receive assigned dose of BBO-10203 orally once daily Patients will receive FOLFOX as infusion every 14 days Patients will receive bevacizumab as infusion every 28 days |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
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Bestemmelse af maksimal tolereret dosis (MTD) og/eller anbefalet fase 2-dosis (RP2D) af BBO-10203 som et enkelt middel
Tidsramme: Op til cirka 5 år
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Op til cirka 5 år
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Procentdel af patienter med behandlingsfremkaldte bivirkninger (TEAE'er), alvorlige bivirkninger (SAE'er) og dosisbegrænsende toksiciteter (DLT'er)
Tidsramme: Op til cirka 5 år
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Op til cirka 5 år
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Anbefalet BBO-10203 dosis i kombination med trastuzumab, fulvestrant +/- ribociclib og folfox + bevacizumab
Tidsramme: Op til cirka 5 år
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Op til cirka 5 år
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Samlet overlevelse (OS)
Tidsramme: Op til cirka 5 år
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Op til cirka 5 år
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Clinical benefit rate (CBR) vurderet af RECIST v1.1.
Tidsramme: Op til cirka 5 år
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Op til cirka 5 år
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Varighed af respons (DOR) som vurderet af RECIST v1.1.
Tidsramme: Op til cirka 5 år
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Op til cirka 5 år
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Progressionsfri overlevelse (PFS) som vurderet af RECIST v1.1
Tidsramme: Op til cirka 5 år
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Op til cirka 5 år
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Areal under koncentration-tid-kurven (AUC
Tidsramme: Foruddosis (inden for 30 minutter) af C1D1 indtil op til ca. 5 år
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Foruddosis (inden for 30 minutter) af C1D1 indtil op til ca. 5 år
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Maksimal plasmakoncentration af lægemiddel (Cmax)
Tidsramme: Foruddosis (inden for 30 minutter) af C1D1 indtil op til ca. 5 år
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Foruddosis (inden for 30 minutter) af C1D1 indtil op til ca. 5 år
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Tid til maksimal plasma-lægemiddelkoncentration (Tmax)
Tidsramme: Foruddosis (inden for 30 minutter) af C1D1 indtil op til ca. 5 år
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Foruddosis (inden for 30 minutter) af C1D1 indtil op til ca. 5 år
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Objektiv svarprocent (ORR) som vurderet af RECIST V1.1 for patienter med målbar sygdom
Tidsramme: Op til cirka 5 år
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Op til cirka 5 år
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Samarbejdspartnere og efterforskere
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Neoplasmer efter sted
- Neoplasmer
- Tarmsygdomme
- Luftvejssygdomme
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Sygdomme i fordøjelsessystemet
- Gastrointestinale sygdomme
- Intestinale neoplasmer
- Endetarmssygdomme
- Lungesygdomme
- Neoplasmer i luftvejene
- Thoracale neoplasmer
- Tyktarmssygdomme
- Neoplastiske processer
- Hudsygdomme
- Brystsygdomme
- Karcinom, bronkogent
- Bronkiale neoplasmer
- Patologiske tilstande, tegn og symptomer
- Hud- og bindevævssygdomme
- Lungeneoplasmer
- Kolorektale neoplasmer
- Brystneoplasmer
- Neoplasma Metastase
- Karcinom, ikke-småcellet lunge
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Aminosyrer, peptider og proteiner
- Proteiner
- Polycykliske forbindelser
- Antistoffer, monoklonal, humaniseret
- Antistoffer, monoklonal
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serum globuliner
- Globuliner
- Steroider
- SMUSED-RING-forbindelser
- Estradiol
- Estrenes
- Estraner
- Estradiol kongenere
- Gonadale steroidhormoner
- Gonadale hormoner
- Trastuzumab
- Fulvestrant
- Bevacizumab
- Ribociclib
- Folfox -protokol
Andre undersøgelses-id-numre
- TBBO10203-101
- 2024-519445-29-00 (Ctis)
- BREAKER-101 (Anden identifikator: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics))
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