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 opdateret af: 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.
Studieoversigt
Status
Rekruttering
Betingelser
Intervention / Behandling
Detaljeret 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.
Undersøgelsestype
Interventionel
Tilmelding (Anslået)
178
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiekontakt
- Navn: Yi Zhu, MD, MBA
- Telefonnummer: 1 908 240 7514
- E-mail: yi.zhu@ionovabio.com
Studiesteder
-
-
Guangdong
-
Guangzhou, Guangdong, Kina
- Rekruttering
- Sun Yat-sen University Cancer Center
-
Ledende efterforsker:
- Ruihua Xu, MD, PhD
-
Kontakt:
- Ruihua Xu
- Telefonnummer: +86 181 2791 2755
- E-mail: Xurh@sysucc.org.cn
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Ingen
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
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Phase 1 INV-8989 Dose escalation Dose level 1
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 1 INV-8989 Dose escalation Dose level 2
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 1 INV-8989 Dose escalation Dose level 3
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 1 INV-8989 Dose escalation Dose level 4
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 1 INV-8989 Dose escalation Dose level 5
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 1 INV-8989 Dose escalation Dose level 6
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 1 INV-8989 Dose escalation Dose level 7
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 1 INV-8989 Dose escalation Dose level 8
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 2a INV-8989 Dose level 1
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 2a INV-8989 Dose level 2
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 2b INV-8989 cohort A
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 2b INV-8989 cohort B
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 2b INV-8989 cohort C
|
INV-8989 is admistered once weekly
|
|
Eksperimentel: Phase 2b INV-8989 cohort D
|
INV-8989 is admistered once weekly
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
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 |
Foranstaltningsbeskrivelse |
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
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
1. juni 2026
Primær færdiggørelse (Anslået)
1. maj 2029
Studieafslutning (Anslået)
1. maj 2029
Datoer for studieregistrering
Først indsendt
14. maj 2026
Først indsendt, der opfyldte QC-kriterier
20. maj 2026
Først opslået (Faktiske)
28. maj 2026
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
10. juni 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
7. juni 2026
Sidst verificeret
1. juni 2026
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Urogenitale sygdomme
- Genitale sygdomme
- Sygdomme i det endokrine system
- Patologiske processer
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Neoplasmer
- Urogenitale sygdomme hos kvinder
- Kvinders urogenitale sygdomme og graviditetskomplikationer
- Tarmsygdomme
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Sygdomme i fordøjelsessystemet
- Gastrointestinale sygdomme
- Kolorektale neoplasmer
- Intestinale neoplasmer
- Endetarmssygdomme
- Livmodersygdomme
- Kønssygdomme, kvindelige
- Neoplasmer i endokrine kirtler
- Galdevejssygdomme
- Neoplastiske processer
- Ovariesygdomme
- Adnexale sygdomme
- Genitale neoplasmer, kvindelige
- Gonadale lidelser
- Uterine neoplasmer
- Patologiske tilstande, tegn og symptomer
- Rektale neoplasmer
- Galdevejsneoplasmer
- Ovariale neoplasmer
- Neoplasma Metastase
- Endometriale neoplasmer
Andre undersøgelses-id-numre
- INV-8989-101 (Registry Identifier: INV-8989-101)
Plan for individuelle deltagerdata (IPD)
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