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

June 7, 2026 updated by: 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

178

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Principal Investigator:
          • Ruihua Xu, MD, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Written informed consent obtained.
  2. Adult patients aged ≥ 18 years.
  3. Patients with histologically or cytologically confirmed locally advanced, unresectable, or metastatic solid tumors harboring the KRAS G12D mutations.
  4. Agree to provide available archived FFPE tumor tissue specimens or voluntarily accept pre-treatment tumor biopsy.
  5. Have RECIST 1.1-defined measurable lesions.
  6. Has a life expectancy of > 3 months.
  7. ECOG performance status 0-1.
  8. Adequate marrow, liver and kidney function.
  9. Meet the study's specified contraceptive requirements.
  10. Meet protocol-specified washout period requirements.

Exclusion Criteria:

  1. Have protocol-defined toxicities within 28 days before the start of study treatment.
  2. Have a second primary malignancy.
  3. Patients with known hypersensitivity to the study drug or any of its components.
  4. Prior history of receiving targeted therapy with specific KRAS G12D inhibitors/degraders or pan-RAS inhibitors/degraders for KRAS G12D mutation.
  5. Has undergone major surgery within 28 days prior to the first dose of study drug.
  6. Patients with symptomatic brain or leptomeningeal metastases.
  7. Patients with other severe and persistent underlying medical conditions as assessed by the Investigator.
  8. Have protocol-defined clinically significant cardiovascular diseases.
  9. Prolonged QTcF interval.
  10. Patients with dyspnea at rest secondary to complications of advanced malignancy, or requiring continuous oxygen therapy due to other medical conditions.
  11. Patients with active pulmonary tuberculosis (TB).
  12. Patients with a known history of interstitial lung disease (ILD).
  13. Patients with a known history of allogeneic solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
  14. Have experienced a severe concurrent infection within 28 days prior to the first dose of study drug.
  15. Patients with congenital or acquired immunodeficiency.
  16. Female patients in pregnancy or lactation period.
  17. Patients with concomitant diseases or conditions deemed by the Investigator likely to interfere with protocol compliance.
  18. Patients unwilling or unable to comply with protocol-specified procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 INV-8989 Dose escalation Dose level 1
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 1 INV-8989 Dose escalation Dose level 2
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 1 INV-8989 Dose escalation Dose level 3
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 1 INV-8989 Dose escalation Dose level 4
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 1 INV-8989 Dose escalation Dose level 5
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 1 INV-8989 Dose escalation Dose level 6
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 1 INV-8989 Dose escalation Dose level 7
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 1 INV-8989 Dose escalation Dose level 8
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 2a INV-8989 Dose level 1
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 2a INV-8989 Dose level 2
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 2b INV-8989 cohort A
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 2b INV-8989 cohort B
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 2b INV-8989 cohort C
Drug: INV-8989
INV-8989 is admistered once weekly
Experimental: Phase 2b INV-8989 cohort D
Drug: INV-8989
INV-8989 is admistered once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Number of participants with treatment-emergent adverse events (TEAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 12 months
To evaluate ORR per RECIST v1.1
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Determine the pharmacokinetics (PK) using AUC of INV-8989
Time Frame: 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
Time Frame: 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)
Time Frame: 12 months
To evaluate ORR per RECIST v1.1
12 months
Phase 1: Evaluate progression free survival (PFS)
Time Frame: 12 months
To evaluate PFS per RECIST v1.1
12 months
Phase 2: Evaluate progression free survival (PFS)
Time Frame: 12 months
To evaluate PFS per RECIST v1.1
12 months
Phase 2: Determine the PK using AUC of INV-8989
Time Frame: 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
Time Frame: 12 months
To determine the PK using Cmax of INV-8989 after a single dose and at steady state after multiple doses
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shenzhen Ionova Life Sciences Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2026

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

May 14, 2026

First Submitted That Met QC Criteria

May 20, 2026

First Posted (Actual)

May 28, 2026

Study Record Updates

Last Update Posted (Actual)

June 10, 2026

Last Update Submitted That Met QC Criteria

June 7, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INV-8989-101 (Registry Identifier: INV-8989-101)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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