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Recruiting NCT07610798

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

Phase I / Phase II Interventional Advance Solid Tumors Colon and Rectal Cancer Non - Small Cell Lung Cancer NSCLC Pancreatic Adenocarcinoma Advanced or Metastatic

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: INV-8989.
Who it may be relevant to
Registry conditions: Advance Solid Tumors, Colon and Rectal Cancer, Non - Small Cell Lung Cancer NSCLC, Pancreatic Adenocarcinoma Advanced or Metastatic. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

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.

Interventions

  • Drug INV-8989
    INV-8989 is admistered once weekly

Primary outcome measures

  • 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]
  • Phase 1: Maximum tolerated dose (MTD) [Time frame: Within first 21 days of treatment]
  • Phase 1: Recommended dose range (RDR) and/or Recommended Phase Ⅱ dose (RP2D) [Time frame: 12 months]
  • Phase 2: Evaluate overall response rate (ORR) [Time frame: 12 months]
Secondary outcome measures (7)
  • Phase 1: Determine the pharmacokinetics (PK) using AUC of INV-8989 [Time frame: 12 months]
  • Phase 1: Determine the PK using Cmax of INV-8989 [Time frame: 12 months]
  • Phase 1: Evaluate overall response rate (ORR) [Time frame: 12 months]
  • Phase 1: Evaluate progression free survival (PFS) [Time frame: 12 months]
  • Phase 2: Evaluate progression free survival (PFS) [Time frame: 12 months]
  • Phase 2: Determine the PK using AUC of INV-8989 [Time frame: 12 months]
  • Phase 2: Determine the PK using Cmax of INV-8989 [Time frame: 12 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

China · 1 center
  • Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07610798 · INV-8989-101 · INV-8989-101

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗