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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Phase 1: Number of participants with treatment-emergent adverse events (TEAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [Срок оценки: 12 months]
• Phase 1: Maximum tolerated dose (MTD) [Срок оценки: Within first 21 days of treatment]
• Phase 1: Recommended dose range (RDR) and/or Recommended Phase Ⅱ dose (RP2D) [Срок оценки: 12 months]
• Phase 2: Evaluate overall response rate (ORR) [Срок оценки: 12 months]

Вторичные конечные точки (7)

• Phase 1: Determine the pharmacokinetics (PK) using AUC of INV-8989 [Срок оценки: 12 months]
• Phase 1: Determine the PK using Cmax of INV-8989 [Срок оценки: 12 months]
• Phase 1: Evaluate overall response rate (ORR) [Срок оценки: 12 months]
• Phase 1: Evaluate progression free survival (PFS) [Срок оценки: 12 months]
• Phase 2: Evaluate progression free survival (PFS) [Срок оценки: 12 months]
• Phase 2: Determine the PK using AUC of INV-8989 [Срок оценки: 12 months]
• Phase 2: Determine the PK using Cmax of INV-8989 [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-sen University Cancer Center — Гуанчжоу

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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