Advanced Solid Tumor, Colorectal Neoplasms, Non-Small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutation, Metastatic Non-Small Lung Cell Cancer, Metastatic Colorectal Cancer (CRC), Metastatic Pancreatic Ductal Adenocarcinoma, KRAS G12A, KRAS G12C, KRAS G12D, KRAS G12S, KRAS G12V, Solid Tumor, Adult, KRAS-mutant, KRAS-positive, KRAS G13D, Pan-KRAS inhibitor, KRAS inhibitor, First-in-human, Solid tumor, Advanced cancer, Adult solid tumor, Metastatic solid tumor, Colorectal cancer, Colon cancer, Rectal cancer, Metastatic colorectal cancer, Pancreatic cancer, Pancreatic ductal adenocarcinoma, PDAC, Metastatic pancreatic cancer, Lung cancer, NSCLC, Precision oncology, Targeted therapy
Brief summary
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.
Detailed description
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.
Interventions
DRUGBLU-924
Tablet
Sponsors
Blueprint Medicines Corporation
Sanofi
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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). 2. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. 4. 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.
Exclusion criteria
1. History of additional malignancy within the last 2 years, with some exceptions as specified in the protocol. 2. Active brain metastases (participants with asymptomatic brain metastases may be eligible). 3. Have received prior targeted treatment(s) against KRAS, including pan-KRAS inhibitors, multi-RAS inhibitors, mutant-selective KRAS inhibitors, and RAS or KRAS degraders. 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation and Enrichment: Percentage of Participants with Dose-limiting Toxicity (DLTs) | Up to 5 years | Any of the prespecified AEs that are attributable to the study treatment, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes. |
| Dose Escalation, Enrichment and Expansion: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs | Up to 5 years | An adverse event (AE) is any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. |
| Dose Escalation and Enrichment: Maximum Tolerated Dose (MTD) of BLU-924 | Up to 5 years | — |
| Dose Escalation and Enrichment: Recommended Dose for Expansion (RDFE) of BLU-924 | Up to 5 years | — |
| Dose Expansion: Overall Response Rate (ORR) | Up to 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Dose Escalation, Enrichment and Expansion: Tmax - Time to Maximum Plasma Drug Concentration for BLU-924 | Up to 2 years |
| Dose Escalation, Enrichment and Expansion: t1/2 - Terminal Half-life of BLU-924 | Up to 2 years |
| Dose Escalation, Enrichment and Expansion: CL/F - Apparent Oral Clearance of BLU-924 | Up to 2 years |
| Dose Escalation and Enrichment: Overall Response Rate (ORR) | Up to 5 years |
| Dose Escalation, Enrichment, and Expansion: Duration of Response (DOR) | Up to 5 years |
| Dose Escalation, Enrichment, and Expansion: Disease Control Rate (DCR) | Up to 5 years |
| Dose Escalation, Enrichment and Expansion: Progression-free Survival (PFS) | Up to 5 years |
| Dose Escalation, Enrichment and Expansion: Vc/F- Apparent Volume of Central Compartment of BLU-924 | Up to 2 years |
| Dose Expansion: Overall Survival (OS) | Up to 5 years |
| Dose Escalation, Enrichment and Expansion: Vd- Volume of Distribution of BLU-924 | Up to 2 years |
| Dose Escalation, Enrichment and Expansion: AUC - Area Under the Plasma Concentration Time Curve for BLU-924 | Up to 2 years |
| Dose Escalation, Enrichment and Expansion: Cmax - Maximum Plasma Concentration for BLU-924 | Up to 2 years |
| Dose Escalation, Enrichment and Expansion: Cmin - Minimum Plasma Concentration of BLU-924 | Up to 2 years |
Countries
United States
Contacts
CONTACTBlueprint Medicines
Outcome results
None listed