A Phase 2 Study of VS-6766 Alone and In Combination with Defactinib in Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- Recurrent KRAS-Mutant (KRAS-MT) Non-Small Cell Lung Cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004265-39-ES
- Lead Sponsor
- Verastem, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 370
1. Male or female subjects = 18 years of age.
2. Histologic or cytologic evidence of NSCLC without histological evidence of a small cell component that is either metastatic (Stage 4) or locally advanced (Stage 3B-C) and unresectable (IASLC 8th edition). The Sponsor’s Medical Monitor must review the
pathology report prior to start of treatment.
3. Subjects must have a known KRAS mutation determined using a validated next-generation
sequencing (NGS) and/or polymerase chain reaction (PCR) testing method prior to enrollment. Adequate material (as defined in the lab manual) must be available prior to study therapy to be used for central confirmation of KRAS mutation status. Central confirmation does not need to be completed prior to enrollment.
a. In Part A of the study, subjects must have either a KRAS-G12V mutation or ANY other KRAS mutation (KRAS-other, including KRAS-G12C).
b. In Part B of the study, subjects must have either a KRAS-G12V mutation or another specific type(s) of KRAS mutation(s) (KRAS-selected), to be determined at the end of Part A.
4. The subject has received appropriate therapy for an activating mutation of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or other activating mutation in which a therapeutic has been approved.
5. The subject has received appropriate platinum-based therapy for a non-activating mutation, such as those mentioned in inclusion criterion #3, and has received appropriate treatment with a monoclonal antibody to PD-1 or PD-L1 unless contraindicated.
6. The subject must have received appropriate treatment with at least one prior systemic
regimen, but no more than 2 prior regimens, for Stage 3B-C or 4 NSCLC.
7. The subject may have previously received adjuvant chemotherapy for earlier stage disease. Adjuvant chemotherapy in early stages will not count as a prior regimen unless disease progression occurred during or within 3 months following adjuvant therapy.
8. Measurable disease according to RECIST 1.1. All radiology studies must be performed within 28 days prior to randomization (Part A) or start of study-directed therapy in Part B.
9. An Eastern Cooperative Group (ECOG) performance status = 1.
10. Must have adequate organ function defined by the following laboratory parameters:
a. Adequate hematologic function including: hemoglobin (Hb) = 9.0 g/dL; platelets
=100,000/mm3 ; and absolute neutrophil count (ANC) = 1500/mm3 ) with no transfusion or growth factor support at least 14 days before first dose of study therapy.
b. Adequate hepatic function: (i) total bilirubin = 1.5 × upper limit of normal (ULN) for the institution; subjects with Gilbert syndrome may enroll if total bilirubin < 3.0 mg/dL (51 µmole/L). (ii) alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) = 2.5 × ULN or < 5x ULN in subjects with liver metastases).
c. Adequate renal function with a creatinine clearance rate of = 60 mL/min as calculated
by the Cockcroft-Gault formula).
d. International normalized ratio (INR) = 1.5 and partial thromboplastin time (PTT) = 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the presence of anticoagulation.
e. Albumin = 3.0 g/dL (451 µmole/L).
f. Creatine phosphokinase (CPK) = 2.5 x ULN.
g. Adequate cardiac function with left ventricular ejection fraction = 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.
11. Baseline QTc interval < 460 ms for women and =450 ms for men (average of triplicate
rea
1. Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
2. History of prior malignancy, with the exception of curatively treated malignancies or malignancies with very low potential for recurrence or progression.
3. Major surgery within 4 weeks (excluding placement of vascular access), minor surgery
within 2 weeks, or palliative radiotherapy within 1 week of the first dose of study therapy.
4. Treatment with warfarin. Subjects on warfarin for DVT/PE can be converted to low-molecular-
weight heparin (LMWH).
5. History of treatment with a direct and specific inhibitor of MEK.
6. History of treatment with a direct and specific inhibitor of KRAS
7. Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy. For additional guidance see https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-
table-substrates-inhibitors-and-inducers.
8. Exposure to P-glycoprotein (P-gp) inhibitors or inducers within 14 days prior to the first dose and
during the course of therapy.
9. Symptomatic brain metastases requiring steroids or other local interventions. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior
to study entry, have discontinued corticosteroid treatment for these metastases for at least 2 weeks prior to first dose of study therapy, and are neurologically stable.
10. Known SARS-Cov2 infection =28 days prior to first dose of study therapy.
11. Known hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection that is
active and/or requires therapy.
12. Active skin disorder that has required systemic therapy within the past 1 year.
13. History of rhabdomyolysis.
14. Concurrent ocular disorders:
a. Subjects with history of glaucoma, history of retinal vein occlusion (RVO),predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
b. Subject with history of retinal pathology or evidence of visible retinal pathology that
is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as measured by
tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO.
c. Subjects with a history of corneal erosion (instability of corneal epithelium), corneal
degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions.
15. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina or severe obstructive pulmonary disease.
16. Subjects with the inability to swallow oral medications or impaired gastrointestinal
absorption due to gastrectomy or active inflammatory bowel disease.
17. Subjects with a history of hypersensitivity to any of the inactive ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational product.
18. Female subjects who are pregnant or breastfeeding.
19. Any other medical condition (e.g. cardiac, gastrointestinal, pulmonary, psychiatric,
neurological, genetic, etc.) that in the opinion of the investigator would places the subject at unacceptably high risk for toxicity.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method