Colorectal Cancer
Conditions
Brief summary
This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab or panitumumab and cetuximab plus mFOLFOX in patients with metastatic KRAS G12D - mutated Colorectal Cancer
Interventions
DRUGVS-7375
Taken by mouth
DRUGcetuximab
Intravenous infusion
DRUGpanitumumab
Intravenous infusion
Intravenous infusion
Sponsors
Verastem, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathology confirmed metastatic CRC * Measurable disease per RECIST 1.1 * Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing) * ECOG PS=0 or 1 2L+ patients: * Must have received at least 1 standard chemotherapy for metastatic colorectal adenocarcinoma * Have documented disease progression during or following their most recent prior line of therapy * Have either stable disease, partial response (PR), or complete response (CR) by RECIST v1.1 as the best overall response (BOR) during at least 1 prior systemic therapy. 1L patients: * Treatment-naïve or received no more than 1 cycle of standard systemic therapy for metastatic disease.
Exclusion criteria
* Have any other documented co-existing common RAS mutation(s) * Prior anti-cancer Tx within 4 weeks or drug-specific timeline within first treatment dose, whichever shorter * Major surgery within 4 weeks of first treatment dose * Radiation therapy (RT) within 1 week of first treatment dose * Receipt of prior direct RAS inhibitor * Receipt of more than 1 investigational therapy * Untreated or symptomatic CNS metastasis * Receipt of strong CYP3A4 inhibitor/inducer or CYP3A4 sensitive substrates with narrow therapeutic index within 14 days or drug-specific timeline within first treatment dose, whichever is shorter * Receipt of PPI or H2 blocker within 5 days * Inability to swallow oral medication * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed ORR by blinded independent central review (BICR) per RESIST v1.1 - 2L CRC only | 6 months | Overall Response Rate per RECIST version 1.1, per blinded independent central review (BICR) |
| To characterize the safety and tolerability of VS-7375 monotherapy or in combination with cetuximab or panitumumab, administered on a daily oral schedule in participants with KRAS G12D-mutated 2L+ CRC | 6 months | Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations |
| To characterize the safety and tolerability of VS-7375 in combination with cetuximab + mFOLFOX, administered on a daily oral schedule in participants with KRAS G12D-mutated 1L CRC | 6 months | Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed ORR per RECIST v1.1 assessed by BICR (primary) and Investigator (secondary) assessments | 24 months | To evaluate additional efficacy parameters of VS-7375 monotherapy and VS-7375 in combination with cetuximab or panitumumab or cetuximab + mFOLFOX, administered on a daily oral schedule in participants with KRAS G12D-mutated CRC |
| Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, Cmax | 20 weeks | Maximum concentration (Cmax) |
| Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, AUC | 20 weeks | Area under plasma Concentration (AUC) 0 to t |
| To evaluate Pharmacodynamics (PD) and other relevant blood tumor markers specific to tumor type | Up to 2.5 years | CA19-9, CEA, CA-125 |
| To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30) | 24 months | The EORTC QLQ-C30 is a validated questionnaire to assess the quality of life of colorectal cancer patients |
| Time to next therapy | 24 months | To assess the interval between initiation of study treatment and initiation of subsequent treatment |
Countries
Australia, United States
Contacts
CONTACTVerastem Call Center
CONTACTLuke Chung, MD
Outcome results
None listed