Clinical Trials in France / NCT07020221
Recruiting
Phase 1/2
A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors
NCT07020221 · tracked via the Priya Life Science France tracker
Condition(s) studied
Pancreatic Ductal AdenocarcinomaNon Small Cell Lung CancerColorectal CancerSolid Tumor, AdultG12D Mutated KRAS
Investigational drug(s) / intervention(s)
VS-7375 →Cetuximab →Carboplatin + Pemetrexed + PembrolizumabAll Carboplatin trials (594) →All Pemetrexed trials (250) →All Pembrolizumab trials (630) →Gemcitabine + Nab-paclitaxelAll Gemcitabine trials (387) →All Nab-paclitaxel trials (237) →Pembrolizumab →Defactinib →Midazolam →Repaglinide →
VS-7375: VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.
Cetuximab: Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).
Carboplatin + Pemetrexed + Pembrolizumab: A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer.
Gemcitabine + Nab-paclitaxel: A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma.
Pembrolizumab: Immunotherapy used as a first-line treatment for advanced non-squamous non-small cell lung cancer.
Defactinib: A potent, selective, reversible inhibitor of focal adhesion kinase that also inhibits proline-rich tyrosine kinase-2
Midazolam: A short-acting benzodiazepine CNS depressant that has sedative, anxiolytic, amnesic, and hypnotic effects.
Repaglinide: A rapid-acting insulin secretagogue used to lower postprandial blood glucose in patients with type 2 diabetes mellitus.
Study summary
This study will assess the safety and efficacy of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation.
Eligibility
Key Inclusion Criteria:
* Individuals ≥18 years of age.
* Agreement to sign and date an informed consent form (ICF) approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
* Histologic or cytologic evidence of locally advanced unresectable or metastatic solid tumor harboring a KRAS G12D mutation.
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate organ function
* Adequate cardiac function
* Recovered from all AEs due to previous therapies to Grade ≤1 or baseline
* Agreement to use highly effective contraception
Key Exclusion Criteria:
* Underwent major surgical procedure as defined by the Investigator, other than for diagnosis, within 4 weeks prior to Cycle 1 Day 1
* Receipt of chemotherapy, targeted therapy, or radiotherapy (excluding palliative radiation) within 4 weeks or 5 half-lives, whichever is shorter, or immunotherapy within 4 weeks prior to Cycle 1 Day 1.
* Treatment with any investigational drug at least 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.
* History of treatment with direct RAS inhibitors.
* Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
* Inability to swallow oral medications.
* Evidence or history of uncontrolled, clinically significant hematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation, neurologic, dermatologic, autoimmune, or allergic disease.
* Individuals who are pregnant or breastfeeding.
Primary outcome measure(s)
- Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 — Up to 2.5 years
To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 as monotherapy administered on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor who have received 1 to 3 lines of prior systemic therapy. Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and DLTs; and abnormal vital signs, physical examination, ECG parameters, ECOG PS, clinical laboratory results; and dose interruptions/reductions. - Part A: To identify the MTD or MFD — Cycle 1 (each cycle is 21 days)
To identify the MTD or MFD using a BOIN design and recommend a dose for subsequent studies of VS-7375 as monotherapy on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor who have received 1 to 3 lines of prior systemic therapy. Proportion/number of participants with DLTs during the DLT assessment period (C1D1 through C1D21). - Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen — Up to 2.5 years
To evaluate the efficacy of the optimal VS-7375 regimen identified from Part A in participants with metastatic KRAS G12D-mutated PDAC who have received 1 line of prior systemic therapy (cohort B1), NSCLC who have received 1 or 2 lines of prior systemic therapy (cohort B2), and other solid tumors who have received 1 or 2 lines of prior systemic therapy (cohort B3). Cohorts B1 and B2: Confirmed ORR by Investigator assessment per RECIST v1.1 . Cohort B3: Confirmed ORR by blinded independent central review (BICR) per RECIST v1.1. - Part C: To characterize the safety, tolerability, and AE profile of VS-7375 in combination regimens. — From enrollment to the end of treatment; an average of 9 months
To characterize the safety, tolerability, and adverse event profile of VS-7375 in combination with: * Cetuximab in participants with advanced/metastatic PDAC after 1 prior systemic therapy, locally advanced/metastatic BTC after 1-2 prior systemic therapies, or metastatic CRC after 1-3 prior systemic therapies (C1) * Carboplatin, pembrolizumab, and pemetrexed in previously untreated metastatic NSCLC (C2) * Gemcitabine and nab-paclitaxel in locally advanced/metastatic PDAC after 1 prior systemic therapy (C3) * Pembrolizumab in locally advanced/metastatic NSCLC after up to 3 prior systemic therapies (C4) * Defactinib in metastatic PDAC or metastatic CRC (C5) Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, DLTs, and dose interruptions/reductions. - Part C: To identify a recommended dose for subsequent studies of combination dosed VS-7375. — Cycle 1 (each cycle is 21 or 28 days)
To identify a recommended dose for subsequent studies of combination dosed VS-7375. Proportion/number of participants with DLTs during the DLT assessment period (through end of Cycle 1). - Part D: To determine the preliminary anticancer activity of the optimal regimen of VS-7375 as identified in Part C — Up to 2.5 years
To determine the efficacy of the optimal regimen of VS-7375 identified in Part C: * In combination with cetuximab in participants with metastatic colorectal adenocarcinoma who have received 1 to 3 prior lines of systemic therapy (cohort D1) * In combination with carboplatin, pembrolizumab, and pemetrexed in participants with previously untreated metastatic NSCLC (cohort D2) * In combination with gemcitabine and nab-paclitaxel in participants with previously untreated metastatic PDAC (cohort D3) Confirmed ORR by Investigator assessment, per RECIST v1.1 . - Part E: To determine the impact of VS-7375 on the PK of midazolam or repaglinide — Up to 2.5 years
AUC of midazolam, repaglinide and relative metabolites. - Part E: To determine the impact of VS-7375 on the PK of midazolam or repaglinide — 2.5 years
Cmax of midazolam, repaglinide and relative metabolites. - Part E: To characterize the safety, tolerability, and AE profile of VS-7375 administered in combination with CYP3A4 and CYP2C8 substrates — 2.5 years
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs and dose interruptions/reductions. - Part F: Serial biopsy — Up to 2.5 years
To characterize the preliminary anti-cancer activity of VS-7375 in participants with metastatic PDAC, correlated with biopsy-obtained biomarkers.
Trial sites (20)
| Facility | City | Region | Status |
|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | Recruiting |
| Johns Hopkins University | Baltimore | Maryland | Recruiting |
| Massachusetts General Hospital | Boston | Massachusetts | Recruiting |
| University of Michigan | Ann Arbor | Michigan | Recruiting |
| Washington University School of Medicine | St Louis | Missouri | Recruiting |
| Laura & Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | Recruiting |
| Univ of Pennsylvania, Abramson Cancer Center | Philadelphia | Pennsylvania | Recruiting |
| SCRI Oncology Partners | Nashville | Tennessee | Recruiting |
| MD Anderson Cancer Center | Houston | Texas | Recruiting |
| Huntsman Cancer Institute | Salt Lake City | Utah | Recruiting |
| University of Virginia | Charlottesville | Virginia | Recruiting |
| Virginia Cancer Specialists | Fairfax | Virginia | Recruiting |
| Virginia Mason Medical Center | Seattle | Washington | Recruiting |
| Macquarie University | Sydney | New South Wales | Recruiting |
| Peninsula and Southeast Oncology | Frankston | Victoria | Recruiting |
| Centre Leon Berard | Lyon | France | Recruiting |
| Centre d'Essais Precoces en Cancerologie de Marseille (CEPCM) | Marseille | France | Recruiting |
| Institut Curie | Paris | France | Recruiting |
| START Madrid - FJD | Madrid | Spain | Recruiting |
| START Madrid CIOCC - Hospital HM Sanchinarro | Madrid | Spain | Recruiting |
On this site
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Other trials for the same condition
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT07020221 on ClinicalTrials.gov ↗ ← All trials in France