A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of INV-8989 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutations
7. juni 2026 oppdatert av: Shenzhen Ionova Life Sciences Co., Ltd.
A Phase I/II, Open-Label, Multi-Center, Dose Escalation and Cohort Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of INV-8989 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutations
This is a Phase 1 and Phase 2 study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of INV-8989 in patients with advanced solid tumors harboring KRAS G12D mutations.
Studieoversikt
Status
Rekruttering
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
This is a Phase 1 and Phase 2 study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of INV-8989 in patients with advanced solid tumors harboring KRAS G12D mutations.
The entire study consists of two parts: Phase 1 for dose escalation and Phase 2 for dose expansion and indication exploration.
Phase 1 dose escalation of INV-8989 follows a real time monitored, PK/PD and safety guided scheme with an accelerated titration plus traditional 3+3 design for DLT assessment.
Phase 2 aims to reassure the safety profile and better define efficacy. Phase 2 consists of Phase 2a and Phase 2b.
Phase 2a study aims to further confirm the safety profile of INV-8989 through a larger number of patients, clarify its PK characteristics and preliminary efficacy, and optimize the recommended Phase 2 dose (RP2D).
The Phase 2b study aims to explore the anti-tumor efficacy of INV-8989 in the patients with different types of advanced solid tumors harboring the KRAS G12D mutation, and those who have failed previous standard treatments.
Studietype
Intervensjonell
Registrering (Antatt)
178
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Yi Zhu, MD, MBA
- Telefonnummer: 1 908 240 7514
- E-post: yi.zhu@ionovabio.com
Studiesteder
-
-
Guangdong
-
Guangzhou, Guangdong, Kina
- Rekruttering
- Sun Yat-sen University Cancer Center
-
Hovedetterforsker:
- Ruihua Xu, MD, PhD
-
Ta kontakt med:
- Ruihua Xu
- Telefonnummer: +86 181 2791 2755
- E-post: Xurh@sysucc.org.cn
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Beskrivelse
Inclusion Criteria:
- Written informed consent obtained.
- Adult patients aged ≥ 18 years.
- Patients with histologically or cytologically confirmed locally advanced, unresectable, or metastatic solid tumors harboring the KRAS G12D mutations.
- Agree to provide available archived FFPE tumor tissue specimens or voluntarily accept pre-treatment tumor biopsy.
- Have RECIST 1.1-defined measurable lesions.
- Has a life expectancy of > 3 months.
- ECOG performance status 0-1.
- Adequate marrow, liver and kidney function.
- Meet the study's specified contraceptive requirements.
- Meet protocol-specified washout period requirements.
Exclusion Criteria:
- Have protocol-defined toxicities within 28 days before the start of study treatment.
- Have a second primary malignancy.
- Patients with known hypersensitivity to the study drug or any of its components.
- Prior history of receiving targeted therapy with specific KRAS G12D inhibitors/degraders or pan-RAS inhibitors/degraders for KRAS G12D mutation.
- Has undergone major surgery within 28 days prior to the first dose of study drug.
- Patients with symptomatic brain or leptomeningeal metastases.
- Patients with other severe and persistent underlying medical conditions as assessed by the Investigator.
- Have protocol-defined clinically significant cardiovascular diseases.
- Prolonged QTcF interval.
- Patients with dyspnea at rest secondary to complications of advanced malignancy, or requiring continuous oxygen therapy due to other medical conditions.
- Patients with active pulmonary tuberculosis (TB).
- Patients with a known history of interstitial lung disease (ILD).
- Patients with a known history of allogeneic solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Have experienced a severe concurrent infection within 28 days prior to the first dose of study drug.
- Patients with congenital or acquired immunodeficiency.
- Female patients in pregnancy or lactation period.
- Patients with concomitant diseases or conditions deemed by the Investigator likely to interfere with protocol compliance.
- Patients unwilling or unable to comply with protocol-specified procedures.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
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 |
|---|---|
|
Eksperimentell: Phase 1 INV-8989 Dose escalation Dose level 1
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 1 INV-8989 Dose escalation Dose level 2
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 1 INV-8989 Dose escalation Dose level 3
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 1 INV-8989 Dose escalation Dose level 4
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 1 INV-8989 Dose escalation Dose level 5
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 1 INV-8989 Dose escalation Dose level 6
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 1 INV-8989 Dose escalation Dose level 7
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 1 INV-8989 Dose escalation Dose level 8
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 2a INV-8989 Dose level 1
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 2a INV-8989 Dose level 2
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 2b INV-8989 cohort A
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 2b INV-8989 cohort B
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 2b INV-8989 cohort C
|
INV-8989 is admistered once weekly
|
|
Eksperimentell: Phase 2b INV-8989 cohort D
|
INV-8989 is admistered once weekly
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Phase 1: Number of participants with treatment-emergent adverse events (TEAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Tidsramme: 12 months
|
The number and percentage of participants with at least one TEAE will be summarized by severity grade and relationship to study drug.
|
12 months
|
|
Phase 1: Maximum tolerated dose (MTD)
Tidsramme: Within first 21 days of treatment
|
The highest dose level at which at least 6 patients have been treated and less than 33% of patients experienced a DLT.
|
Within first 21 days of treatment
|
|
Phase 1: Recommended dose range (RDR) and/or Recommended Phase Ⅱ dose (RP2D)
Tidsramme: 12 months
|
The RDR and/or RP2D will be determined based on the PK and PD data, the preliminary clinical activity of INV-8989, as well as the incidence rate and nature of the toxicities observed in subsequent cycles beyond Cycle 1.
|
12 months
|
|
Phase 2: Evaluate overall response rate (ORR)
Tidsramme: 12 months
|
To evaluate ORR per RECIST v1.1
|
12 months
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Phase 1: Determine the pharmacokinetics (PK) using AUC of INV-8989
Tidsramme: 12 months
|
To determine the (PK) using AUC of INV-8989 after a single dose and at steady state after multiple doses
|
12 months
|
|
Phase 1: Determine the PK using Cmax of INV-8989
Tidsramme: 12 months
|
Determine the PK using Cmax of INV-8989 after a single dose and at steady state after multiple doses
|
12 months
|
|
Phase 1: Evaluate overall response rate (ORR)
Tidsramme: 12 months
|
To evaluate ORR per RECIST v1.1
|
12 months
|
|
Phase 1: Evaluate progression free survival (PFS)
Tidsramme: 12 months
|
To evaluate PFS per RECIST v1.1
|
12 months
|
|
Phase 2: Evaluate progression free survival (PFS)
Tidsramme: 12 months
|
To evaluate PFS per RECIST v1.1
|
12 months
|
|
Phase 2: Determine the PK using AUC of INV-8989
Tidsramme: 12 months
|
Determine the PK using AUC of INV-8989 after a single dose and at steady state after multiple doses
|
12 months
|
|
Phase 2: Determine the PK using Cmax of INV-8989
Tidsramme: 12 months
|
To determine the PK using Cmax of INV-8989 after a single dose and at steady state after multiple doses
|
12 months
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
1. juni 2026
Primær fullføring (Antatt)
1. mai 2029
Studiet fullført (Antatt)
1. mai 2029
Datoer for studieregistrering
Først innsendt
14. mai 2026
Først innsendt som oppfylte QC-kriteriene
20. mai 2026
Først lagt ut (Faktiske)
28. mai 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
10. juni 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
7. juni 2026
Sist bekreftet
1. juni 2026
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Urogenitale sykdommer
- Kjønnssykdommer
- Sykdommer i det endokrine systemet
- Patologiske prosesser
- Urogenitale neoplasmer
- Neoplasmer etter nettsted
- Neoplasmer
- Kvinnelige urogenitale sykdommer
- Kvinnelige urogenitale sykdommer og graviditetskomplikasjoner
- Tarmsykdommer
- Gastrointestinale neoplasmer
- Neoplasmer i fordøyelsessystemet
- Sykdommer i fordøyelsessystemet
- Gastrointestinale sykdommer
- Kolorektale neoplasmer
- Intestinale neoplasmer
- Rektale sykdommer
- Livmorsykdommer
- Kjønnssykdommer, kvinner
- Neoplasmer i endokrine kjertel
- Galleveissykdommer
- Neoplastiske prosesser
- Sykdommer i eggstokkene
- Adnexal sykdommer
- Genitale neoplasmer, kvinnelige
- Gonadal lidelser
- Uterine neoplasmer
- Patologiske tilstander, tegn og symptomer
- Rektale neoplasmer
- Neoplasmer i galleveiene
- Neoplasmer i eggstokkene
- Neoplasma Metastase
- Endometriale neoplasmer
Andre studie-ID-numre
- INV-8989-101 (Registeridentifikator: INV-8989-101)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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