A First-in-Human Trial of BLU-924 (SAR449336) in Advanced Solid Tumors Harboring KRAS Mutations

Официальное название

A Phase 1/2, Open-Label, Dose-Escalation, Dose-Enrichment, and Dose-Expansion Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of BLU-924 (SAR449336) as Monotherapy and Combination Therapy in Participants With Advanced Pancreatic Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer Harboring KRAS Mutations

Обзор

A first in human study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of BLU-924 / SAR449336, a pan-KRAS inhibitor, in participants with advanced Pancreatic Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer harboring KRAS mutations.

Подробное описание

This is an open-label, multi-center, Phase 1/2 study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of BLU-924, a pan-KRAS inhibitor, in participants with metastatic KRAS mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), or colorectal cancer (CRC). The monotherapy part of the study includes Dose Escalation, Dose Enrichment, and Dose Expansion. Participants enrolled during Dose Escalation and Dose Enrichment will be evaluated for dose limiting toxicities (DLTs) to determine the MTD. Participants enrolled into disease-specific Enrichment cohorts will enable a more robust characterization of safety, PK, pharmacodynamics, and preliminary clinical activity. Enrolment into Dose Expansion will follow the identification of at least 1 recommended dose for expansion (RDFE) based on data from the Dose Escalation and Dose Enrichment. No combination arm is active at this time.

Вмешательства

• Препарат BLU-924
  Tablet

Первичные конечные точки

• Dose Escalation and Enrichment: Percentage of Participants with Dose-limiting Toxicity (DLTs) [Срок оценки: Up to 5 years]
• Dose Escalation, Enrichment and Expansion: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs [Срок оценки: Up to 5 years]
• Dose Escalation and Enrichment: Maximum Tolerated Dose (MTD) of BLU-924 [Срок оценки: Up to 5 years]
• Dose Escalation and Enrichment: Recommended Dose for Expansion (RDFE) of BLU-924 [Срок оценки: Up to 5 years]
• Dose Expansion: Overall Response Rate (ORR) [Срок оценки: Up to 5 years]

Вторичные конечные точки (12)

• Dose Escalation and Enrichment: Overall Response Rate (ORR) [Срок оценки: Up to 5 years]
• Dose Escalation, Enrichment, and Expansion: Duration of Response (DOR) [Срок оценки: Up to 5 years]
• Dose Escalation, Enrichment, and Expansion: Disease Control Rate (DCR) [Срок оценки: Up to 5 years]
• Dose Escalation, Enrichment and Expansion: Progression-free Survival (PFS) [Срок оценки: Up to 5 years]
• Dose Expansion: Overall Survival (OS) [Срок оценки: Up to 5 years]
• Dose Escalation, Enrichment and Expansion: AUC - Area Under the Plasma Concentration Time Curve for BLU-924 [Срок оценки: Up to 2 years]
• Dose Escalation, Enrichment and Expansion: Cmax - Maximum Plasma Concentration for BLU-924 [Срок оценки: Up to 2 years]
• Dose Escalation, Enrichment and Expansion: Cmin - Minimum Plasma Concentration of BLU-924 [Срок оценки: Up to 2 years]
• Dose Escalation, Enrichment and Expansion: Tmax - Time to Maximum Plasma Drug Concentration for BLU-924 [Срок оценки: Up to 2 years]
• Dose Escalation, Enrichment and Expansion: t1/2 - Terminal Half-life of BLU-924 [Срок оценки: Up to 2 years]
• Dose Escalation, Enrichment and Expansion: CL/F - Apparent Oral Clearance of BLU-924 [Срок оценки: Up to 2 years]
• Dose Escalation, Enrichment and Expansion: Vc/F- Apparent Volume of Central Compartment of BLU-924 [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Pathologically confirmed diagnosis of metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) with evidence of a single KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA).
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Patients must have received all standard therapies for their cancer type in the metastatic setting, unless they are unable to receive such therapies due to clinical characteristics, comorbidities, or other medically justified reasons.

Критерии исключения

• History of additional malignancy within the last 2 years, with some exceptions as specified in the protocol.
• Active brain metastases (participants with asymptomatic brain metastases may be eligible).
• Have received prior targeted treatment(s) against KRAS, including pan-KRAS inhibitors, multi-RAS inhibitors, mutant-selective KRAS inhibitors, and RAS or KRAS degraders.
• Active or uncontrolled systemic infection, such as tuberculosis, Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Next Oncology Virginia Cancer Specialist — Fairfax

Идентификаторы

NCT: NCT07629960 · BLU-924-1101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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