Studie av ARTS-021 hos pasienter med avanserte solide svulster
En fase 1/2, første-i-menneske-studie for å vurdere sikkerhet, tolerabilitet, farmakokinetikk, farmakodynamikk, MTD/RP2D og antitumoraktivitet til ARTS-021 som enkeltmiddel og i kombinasjonsterapi hos pasienter med solide svulster
This study, the first clinical trial of AVZO-021, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and anti-tumor effects of AVZO-021 in patients with advanced solid tumors. AVZO-021 is an oral medication that inhibits cyclin-dependent kinase 2 (CDK 2).
Studieoversikt
Status
Forhold
Detaljert beskrivelse
AVZO-021 is a compound being developed for the treatment of patients with advanced solid tumors, specifically, HR+/HER2- breast cancer and cyclin E1 (CCNE1) altered malignancies. AVZO-021 is a selective and potent cyclin-dependent kinase 2 (CDK2) inhibitor, which plays an important role in cell cycle regulation. This is a Phase 1/2 first-in-human, open-label, nonrandomized, multicenter study of AVZO-021. Phase 1 is a dose-escalation phase aimed at assessing the safety and tolerability of AVZO-021 and determining the recommended phase 2 dose (RP2D) as monotherapy and combination therapy. Phase 2 is a dose-expansion phase that will be conducted to assess the antitumor activity of AVZO-021 as monotherapy and combination therapy.
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: Medical Information
- Telefonnummer: (858) 239-2944
- E-post: ClinicalTrials@avenzotx.com
Studiesteder
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New South Wales
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Macquarie University, New South Wales, Australia
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Wollongong, New South Wales, Australia
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Connecticut
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New Haven, Connecticut, Forente stater, 06520
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Florida
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Sarasota, Florida, Forente stater, 34232
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Tampa, Florida, Forente stater, 33612
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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New York
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Mineola, New York, Forente stater, 11501
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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New York, New York, Forente stater, 10016
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Ohio
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Cleveland, Ohio, Forente stater, 44106
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Oklahoma
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Oklahoma City, Oklahoma, Forente stater, 73117
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Oregon
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Portland, Oregon, Forente stater, 97213
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19107
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Texas
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Dallas, Texas, Forente stater, 75246
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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Virginia
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Fairfax, Virginia, Forente stater, 22031
- Rekruttering
- Avenzo Therapeutics Recruiting Site
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Ta kontakt med:
- Avenzo Therapeutics
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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:
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Male or female aged ≥18 years old at screening with Eastern Cooperative Oncology Group (ECOG) 0-1.
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Disease-related inclusion criteria by study phase and part:
i) Phase 1a Monotherapy Dose Escalation: Patients with locally advanced or metastatic HR+/HER2- breast cancer, CCNE1-amplified tumors that are either epithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer, endometrial cancer or TNBC, with no other oncogenic driver mutations that are treatable and standard therapies are no longer effective, appropriate, or safe in the opinion of the investigator and medical monitor. Patients with any additional tumor type with CCNE1 amplification can be enrolled only if clinical data is supportive and approved by medical monitor (Cohort 1A).
ii) Phase 1b Combination Dose Escalation: histologically or cytologically confirmed diagnosis of locally advanced or metastatic HR+ HER2- (HER2-low may be allowed if failed standard of care therapy) breast cancer, who have been previously treated with inhibitor of CDK4/6 and endocrine therapy(Cohorts 1B1, 1B2, 1B3, 1B4, and 1B5); or histologically or cytologically confirmed diagnosis of CCNE1- amplified, locally advanced or metastatic, platinum-refractory or platinum-resistant EOC, primary peritoneal, or fallopian tube cancer (Cohort 1C).
iii) Phase 2a Monotherapy dose expansion: Histologically or cytologically confirmed diagnosis of locally advanced or metastatic CCNE1 amplified epithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer, endometrial cancer or TNBC, with no other oncogenic driver mutations that are treatable and standard therapies are no longer effective, appropriate, or safe in the opinion of the investigator and medical monitor (Cohort 2A).
iv) Phase 2b Combination dose expansion: Histologically or cytologically confirmed diagnosis of locally advanced or metastatic HR+/HER2- (HER2-low may be allowed if failed standard of care therapy) breast cancer who have been previously treated with no more than 1 prior CDK4/6 inhibitor and endocrine therapy (Cohorts 2B1, 2B2, 2B3, 2B4, and 2B5); or Histologically or cytologically confirmed diagnosis of locally advanced or metastatic, CCNE1-amplified, platinum-refractory or platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer (Cohort 2C).
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No more than 2 prior cytotoxic chemotherapy regimens for locally advanced/metastatic disease (excepting patients treated with an antibody-drug conjugate, with ovarian cancer if there disease is platinum resistant or refractory, having progressed beyond all SOC care; and patients who have received prior chemotherapy in the adjuvant or neoadjuvant setting >12 months prior to starting AVZO-021 treatment).
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Measurable disease as determined by RECIST version 1.1.
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Adequate bone marrow and organ function.
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Ability to swallow capsules or tablets.
Key Exclusion Criteria:
- Received an investigational agent or anticancer therapy within 2 weeks, or 5 half-lives of the drug, whichever is shorter, prior to planned start of AVZO-021.
- Received any CDK2 inhibitor, protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) inhibitor, or WEE1 inhibitor anticancer therapy. For cohort B5, prior therapy with topoisomerase inhibitors is not permitted.
- Undergone major surgery within 4 weeks prior to planned start of AVZO-021.
- Received radiotherapy for palliation within 7 days of the first dose of study treatment, unless specified otherwise in the protocol.
- Active CNS metastases or confirmed leptomeningeal disease are not eligible.
- Unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade >1 at the time of starting study treatment.
- Clinically unstable cardiac function as described in the protocol.
- Any active or chronic infection/disease that compromises the immune system.
- Current treatment with strong or moderate cytochrome P450 (CYP)3A4 inhibitors or inducers.
- Active second malignancy unless in remission with life expectancy > 2 years and with documented sponsor approval.
- Pregnancy, lactation, or plans to breastfeed during the study or within 6 months of the last dose of study intervention.
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: Phase 1, monotherapy (Part 1A)
Escalating doses of once daily, oral AVZO-021 in 28-day cycles. |
AVZO-021 is a selective and potent oral inhibitor of CDK2 being developed for the treatment of patients with advanced solid tumors with CDK2 dependency (1A), CCNE1 amplified solid tumors (2A), HR+/HER2- BC (1B1-1B5, 2B1-2B5) and CCNE1 amplified EOC (1C, 2C) |
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Eksperimentell: Phase 1, combination (Parts 1B and 1C)
Escalating doses of once daily, oral AVZO-021 in 28-day cycles starting at least 1 DL below the monotherapy MTD/RP2D dose in combination with: 1B1) fulvestrant 1B2) palbociclib plus either fulvestrant or letrozole 1B3) ribociclib plus either fulvestrant or letrozole 1B4) abemaciclib plus either fulvestrant or letrozole 1B5) sacituzumab govitecan-hziy 1C) carboplatin |
AVZO-021 is a selective and potent oral inhibitor of CDK2 being developed for the treatment of patients with advanced solid tumors with CDK2 dependency (1A), CCNE1 amplified solid tumors (2A), HR+/HER2- BC (1B1-1B5, 2B1-2B5) and CCNE1 amplified EOC (1C, 2C) Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
Andre navn:
Antineoplastic agent, estrogen receptor antagonist
Andre navn:
Antineoplastic agent, aromatase inhibitor
Andre navn:
Antineoplastic CDK4/6 inhibitor
Andre navn:
Antineoplastic CDK4/6 inhibitor
Andre navn:
Alkylating agent Trop-2 antibody and topoisomerase inhibitor
Andre navn:
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Eksperimentell: Phase 2, monotherapy (Part 2A)
Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Part 1A. |
AVZO-021 is a selective and potent oral inhibitor of CDK2 being developed for the treatment of patients with advanced solid tumors with CDK2 dependency (1A), CCNE1 amplified solid tumors (2A), HR+/HER2- BC (1B1-1B5, 2B1-2B5) and CCNE1 amplified EOC (1C, 2C) |
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Eksperimentell: Phase 2, combination (Parts 2B and 2C)
Oral doses of AVZO-021 in 28-day cycles at the RP2D determined in Parts 1B/1C, in combination with: 2B1) fulvestrant 2B2) palbociclib plus either fulvestrant or letrozole 2B3) ribociclib plus either fulvestrant or letrozole 2B4) abemaciclib plus either fulvestrant or letrozole 2B5) sacituzumab govitecan-hziy 2C) carboplatin |
AVZO-021 is a selective and potent oral inhibitor of CDK2 being developed for the treatment of patients with advanced solid tumors with CDK2 dependency (1A), CCNE1 amplified solid tumors (2A), HR+/HER2- BC (1B1-1B5, 2B1-2B5) and CCNE1 amplified EOC (1C, 2C) Antineoplastic agent, cyclin-dependent kinase 4/6 inhibitor
Andre navn:
Antineoplastic agent, estrogen receptor antagonist
Andre navn:
Antineoplastic agent, aromatase inhibitor
Andre navn:
Antineoplastic CDK4/6 inhibitor
Andre navn:
Antineoplastic CDK4/6 inhibitor
Andre navn:
Alkylating agent Trop-2 antibody and topoisomerase inhibitor
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Occurrence of Dose Limiting Toxicities (DLTs) during the first cycle (Phase 1)
Tidsramme: 28 Days
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Number of participants with DLTs assessed for severity using CTCAE v5.0 criteria will be summarized by dose level. |
28 Days
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Number of Participants with Treatment Emergent Adverse Events (TEAEs) and lab abnormalities (Phase 1)
Tidsramme: Approximately 22 months
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To evaluate the type, incidence, severity, timing, seriousness, and relationship to study treatment of adverse events and any laboratory abnormalities summarized by dose level. |
Approximately 22 months
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Determination of Recommended Phase 2 Dose (RP2D) (Phase 1)
Tidsramme: Approximately 16 months
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RP2D for AVZO-021 is less than or the same as the maximum tolerated dose (MTD) as defined by the occurrence of DLTs and TEAEs calculated using isotonic regression. |
Approximately 16 months
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Objective Response Rate (ORR) (Phase 2)
Tidsramme: Approximately 52 months
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Defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1. |
Approximately 52 months
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Progression Free Survival (PFS) (Phase 2)
Tidsramme: Approximately 52 months
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Defined as the time from study drug treatment to death or disease progression, as determined by the investigator by radiographic disease assessment according to RECIST v1.1. |
Approximately 52 months
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Overall Survival (OS) (Phase 2)
Tidsramme: Approximately 76 months
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Defined as the time from study drug treatment initiation to death from any cause. |
Approximately 76 months
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Duration of response (DOR) (Phase 2)
Tidsramme: Approximately 52 months
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Defined as the time from the first confirmed response to radiologic/objective progression. |
Approximately 52 months
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Sekundære resultatmål
Resultatmål |
Tidsramme |
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PK-parametre: Maksimal plasmakonsentrasjon (Cmax) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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PK-parametre: Tid til maksimal plasmakonsentrasjon (Tmax) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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PK-parametre: Areal under plasmakonsentrasjon-tid-kurven fra tid 0 til siste målbare konsentrasjon (AUC 0-sist) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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PK-parametre: Areal under plasmakonsentrasjon-tid-kurven fra tid 0 til siste målbare konsentrasjon (AUC 0-tau) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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PK-parametre: Minimum observert plasmakonsentrasjon ved steady state (Cmin, ss) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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PK-parametere: Akkumulasjonsrasjon (Rac) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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PK-parametre: Eliminasjonshalveringstid (t1/2) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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PK-parametere: Tilsynelatende clearance (CL/F) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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PK-parametre: Tilsynelatende distribusjonsvolum under terminalfase (Vz/F) (monoterapi og kombinasjon)
Tidsramme: Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Syklus 1 dag 1, 2, 8, 14 og 15 (hver syklus er 28 dager)
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Vurder effekten av et fettrikt måltid på PK av AVZO-021 (fase 1)
Tidsramme: 5 dager
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5 dager
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Samarbeidspartnere og etterforskere
Sponsor
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
- Urogenitale sykdommer
- Kjønnssykdommer
- Sykdommer i det endokrine systemet
- Urogenitale neoplasmer
- Neoplasmer etter nettsted
- Neoplasmer
- Kvinnelige urogenitale sykdommer
- Kvinnelige urogenitale sykdommer og graviditetskomplikasjoner
- Neoplasmer etter histologisk type
- Livmorsykdommer
- Kjønnssykdommer, kvinner
- Neoplasmer i endokrine kjertel
- Neoplasmer, kjertel og epitel
- Sykdommer i eggstokkene
- Adnexal sykdommer
- Genitale neoplasmer, kvinnelige
- Gonadal lidelser
- Hudsykdommer
- Bryst sykdommer
- Karsinom
- Uterine neoplasmer
- Eggledersykdommer
- Neoplasmer i eggstokkene
- Hud- og bindevevssykdommer
- Karsinom, ovarieepitel
- Brystneoplasmer
- Trippel negative brystneoplasmer
- Endometriale neoplasmer
- Egglederneoplasmer
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Organiske kjemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Azoler
- Polysykliske forbindelser
- Koordinasjonskomplekser
- Steroider
- Smeltede ringforbindelser
- Nitriles
- Estradiol
- Estrenes
- Østraner
- Estradiol -kongener
- Gonadal steroidhormoner
- Gonadalhormoner
- Triazoler
- Letrozol
- Fulvestrant
- Karboplatin
- Abemaciclib
- ribociclib
- palbociclib
- Sacituzumab Govitecan
Andre studie-ID-numre
- AVZO-021-1001
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
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Studerer et amerikansk FDA-regulert enhetsprodukt
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