Non-Small Cell Lung Cancer
Conditions
Brief summary
This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab in patients with metastatic KRAS G12D - mutated Non-Small Cell Lung Cancer
Interventions
DRUGVS-7375
Taken by mouth
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 unresectable locally advanced or metastatic NSCLC * Measurable disease per RECIST 1.1 * Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing) * ECOG PS=0 or 1 * Adequate organ function * Received prior treatment with a platinum-based chemotherapy regimen and an immune checkpoint inhibitor in the advanced, non-resectable setting. * Have documented disease progression during or following their most recent prior line of therapy. Patients with 2L/3L on stable or preferred dose: * Received at least 1 and no more than 2 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC. Patients with 2L-4L with brain metastases: * Received at least 1 and no more than 3 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC. * Have asymptomatic and untreated brain metastases * At least 1 untreated measurable brain lesion per mRECIST v1.1 with a long axis ≥ 0.5 cm and ≤ 3 cm.
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 * History of drug-induced Interstitial Lung Disease * Receipt of prior direct RAS inhibitor * 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 | 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 administered on a daily oral schedule in participants with KRAS G12D-mutated NSCLC | 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 administered on a daily oral schedule in participants with KRAS G12D-mutated NSCLC |
| 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 non-small cell lung cancer patients |
| Time to next therapy | 24 months | To assess the interval between initiation of study treatment and initiation of subsequent treatment |
Countries
United States
Contacts
CONTACTVerastem Call Center
CONTACTTing Wu, MD
Outcome results
None listed