G12D Mutated KRAS, Pancreatic Ductal Adenocarcinoma (PDAC)
Conditions
Keywords
KRAS G12D mutation, KRAS, PDAC, Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer, Pancreatic Neoplasms, RAS
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 Pancreatic Cancer
Interventions
DRUGVS-7375
Taken by mouth
DRUGcetuximab
Subcutaneous 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 PDAC * 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 VS-7375 + cetuximab (2L PDAC) : -Received only 1 prior Tx in the metastatic setting; prior adjuvant counts as a line if progressed within 6 months VS-7375 + cetuximab (1L PDAC) : -Treatment-naïve or received ≤ 1 cycle of SoC 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; RT to brain or lung within 2 weeks 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 or in combination with cetuximab, administered on a daily oral schedule in participants with KRAS G12D-mutated PDAC. | 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, administered on a daily oral schedule in participants with KRAS G12D-mutated PDAC. |
| 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 pancreatic ductal adenocarcinoma patients |
| Time to next therapy. | 24 months | To assess the interval between initiation of study treatment and initiation of subsequent |
Countries
Australia, United States
Contacts
CONTACTVerastem Call Center
CONTACTLuke Chung, MD
Outcome results
None listed