Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas

NCT03808558 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU 022017-058
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This is a prospective one-arm, two-stage phase 2 trial of TVB-2640 in KRAS mutant NSCLC patients. 13 patients will be treated with a minimum of 1 cycle of TVB-2640 therapy over 8 weeks.

Conditions

KRAS Gene Mutation

Outcome Measures

Primary Outcomes (2)

• Disease control rate of TVB-2640

  Determine Disease control rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.

  every 8 weeks through study completion, an average of 1 year

• Response rate of TVB-2640

  Determine response rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.

  every 8 weeks through study completion, an average of 1 year

Secondary Outcomes (4)

• Safety profile of TVB-2640

  Pretreatment and four weeks of treatment.

• Establish the predictive value of 11C-acetate PET

  Pretreatment and four weeks of treatment.

• Mean change in fasting plasma lipidomics

  Pretreatment and four weeks of treatment.

• Mean change in sebaceous secretion of fatty acids

  Pretreatment and four weeks of treatment.

Study Arms (1)

TVB-2640

EXPERIMENTAL

Patients will be administered TVB-2640 100mg/m2 orally once a day for 8 weeks.

Drug: TVB-2640

Interventions

TVB-2640 DRUG

TVB-2640 will be administered 100mg/m2 orally once a day for 8 weeks.

TVB-2640

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic or advanced stage, histologically or cytologically confirmed NSCLC and molecular identification of oncogenic KRAS mutation.
• KRAS mutant NSCLC must be refractory, relapsed, and previously treated with doublet chemotherapy and immune checkpoint inhibitor (unless there is a specific contraindication to checkpoint inhibitor).
• Molecular characterization (tissue- or blood-based \[ie, cell-free/circulating tumor DNA\]) must have been performed and must have demonstrated an oncogenic KRAS mutation (e.g., exon 12, 13, 61, or 117 mutation detected by sequencing) by a CLIA-certified assay (source documentation required). KRAS mutations at other codons require review and approval by Study Chair.
• Subjects' EGFR mutation and ALK gene rearrangement status must be known prior to study entry. Subjects with EGFR mutation or ALK gene rearrangement must have progressed after appropriate FDA-approved targeted therapy options prior to eligibility.
• Patient has evidence of disease progression on most recent line of therapy.
• Patient has measurable disease by RECIST v1.1 (Eisenhauer, 2009).
• Age ≥ 18 years.
• ECOG performance status of 0 or 1.
• Predicted life expectancy of \>3 months.
• Adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 75,000/mcL
• total bilirubin \<2X institutional upper limit of normal
• AST and ALT ≤5X institutional upper limit of normal
• serum creatinine \<1.5X institutional upper limit of normal

You may not qualify if:

• Patient is unable to swallow oral medications or has impairment of GI function or GI disease that may significantly alter drug absorption such as active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome.
• Patient has a history of risk factors for torsade de pointes such as uncontrolled heart failure, severe hypokalemia with potassium less than 3mM/L, history of long QT syndrome or require use during study participation of concomitant medications known to prolong QT/QTc interval.
• Patients who require use of strong CYP3A4/5 agonists or inhibitors during study participation.
• Patient has uncontrolled or severe intercurrent medical condition including uncontrolled brain metastases. Patients with stable brain metastases either treated or untreated, on a stable dose of steroids/anticonvulsants, with no dose increase within 4 weeks before the first dose of TVB-2640, and no anticipated dose change, are allowed.
• Patient underwent major surgery within 4 weeks before the first dose of TVB-2640 or received cancer-directed therapy either chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc. or an investigational drug or device within 2 weeks (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent, whichever is shorter before the first dose of TVB-2640. In addition, any drug- related toxicity, with the exception of alopecia, an endocrinopathy controlled with replacement therapy, or a clinically stable toxicity not expected to increase from study therapy (eg, cisplatin-associated ototoxicity) should have recovered to \<Grade 1.
• If female, patient is pregnant or breast-feeding.
• Patient has evidence of a serious active infection-infection requiring treatment with intravenous antibiotics.
• Patient has known immunodeficiency virus-HIV or hepatitis B or C infection, as such patients may be at increased risk for toxicity due to concomitant treatment and disease-related symptoms may preclude accurate assessment of the safety of TVB-2640.
• Patient has an important medical illness or abnormal laboratory finding that, in the Investigator's opinion, would increase the risk of participating in this study.
• Patients with prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational agent.
• History of clinically significant dry eye (xerophthalmia) or other corneal abnormality or, if a contact lens wearer, does not agree to abstain from contact lens use from baseline through the last study drug dose.
• Patient has a known allergy or hypersensitivity to components of TVB-2640.
• Patient has a prior history of hypersensitivity, drug/radiation-induced, or other immune-mediated pneumonitis.

Sponsors & Collaborators

• David E Gerber: lead
• Sagimet Biosciences Inc.: collaborator
• Cancer Prevention Research Institute of Texas: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (2)

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9179, United States

Location

MeSH Terms

Interventions

TVB-2640

Study Officials

• David Gerber, MD

  Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PROFESSOR - Internal Medicine

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: January 17, 2019
• Study Start: September 11, 2019
• Primary Completion: April 3, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)