What is the Purpose of this Study?
Primary Objective: Part A: VS-7375 Single Agent Dose Escalation To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 as 2L+ monotherapy administered on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor. To identify the MTD or MFD using a BOIN design and recommend a dose for subsequent studies of VS-7375 as 2L+ monotherapy on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor Part B: VS-7375 Single-Agent Dose Expansion To evaluate the preliminary anticancer activity of the optimal VS-7375 2L+ regimen identified from Part A in participants with advanced or metastatic KRAS G12D-mutated PDAC (cohort B1), NSCLC (cohort B2), and other solid tumors (cohort B3) Part C: VS-7375 Combination Dose Escalation To characterize the safety, tolerability, and AE profile of VS-7375 as: 2L+ therapy in combination with cetuximab in participants with any advanced or metastatic solid tumor harboring a KRAS G12D mutation 1L therapy in combination with carboplatin, pembrolizumab, and pemetrexed in participants with previously untreated metastatic NSCLC 2L+ therapy in combination with gemcitabine and nab-paclitaxel in participants with metastatic PDAC 1L therapy in combination with gemcitabine in participants aged 75 years or older with previously untreated metastatic PDAC. To identify a recommended dose for subsequent studies of combination dosed VS-7375. Part D: Cetuximab and VS-7375 Combination Dose Expansion To determine the preliminary anticancer activity of the optimal cetuximab + VS-7375 regimen identified from Part C in participants with advanced KRAS G12Dmutated CRC Part D: VS-7375 Combination Dose Expansion To determine the preliminary anticancer activity of the optimal regimen of VS-7375 identified in Part C as: 2L+ therapy in combination with cetuximab in participants with metastatic colorectal adenocarcinoma 1L therapy in combination with carboplatin, pembrolizumab, and pemetrexed in participants with previously untreated metastatic NSCLC 2L+ therapy in combination with gemcitabine and nab-paclitaxel in participants with metastatic PDAC 1L therapy in combination with gemcitabine in participants aged 75 years or older with previously untreated metastatic PDAC. Secondary Objectives: Part A To characterize the PK of VS-7375 as 2L+ monotherapy administered on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor. To evaluate the preliminary anticancer activity of VS-7375 as 2L+ monotherapy in participants with any KRAS G12D-mutated solid tumor Parts B and D To characterize the safety, tolerability, and AE profile of the recommended VS-7375 regimens from Part A (VS-7375 monotherapy) and Part C (VS-7375 in combination with other systemic therapies), administered on a daily oral schedule in participants with KRAS G12D-mutated solid tumors. Parts B, C, and D To continue to evaluate the PK of VS-7375 as monotherapy and in combination with other systemic therapies in participants with KRAS G12D-mutated advanced solid tumors. Part C, Cohort C3 To evaluate the impact of VS-7375 on nab-paclitaxel PK in cohort C3
Eligibility
- * 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.
- * Must have received ≥1 prior line of standard systemic therapy for advanced or metastatic disease or experienced cancer progression within 6 months of neoadjuvant or adjuvant therapy.
Where can I participate?
- CS Cancer at Cedars-Sinai Medical Center : Shannon Cyhan
- CS Cancer at The Angeles Clinic and Research Institute : Shannon Cyhan
More about this Clinical Trial
What is the full name of this clinical trial?
VS-7375-101: A Phase 1/2a, Open-label Study of VS-7375, a KRAS G12D Inhibitor, as Monotherapy and in Combination, in Patients with Advanced KRAS G12D-Mutant Solid Tumors