We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03808558
Recruitment Status : Recruiting
First Posted : January 17, 2019
Last Update Posted : February 21, 2022
Sponsor:
Collaborators:
Sagimet Biosciences Inc.
Cancer Prevention Research Institute of Texas
Information provided by (Responsible Party):
David E Gerber, University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
KRAS Gene Mutation Drug: TVB-2640 Phase 2

Detailed Description:

Patients with stable disease or partial/complete remissions will continue therapy.

The endpoints are response rate-RR, disease control rate-DCR, PFS-progression-free survival, CTCAEv5.0 toxicities, plasma lipid levels, collection of sebaceous secretion via Sebutape, and 11C-acetate PET tumor imaging.

In the first stage, 13 patients will be enrolled. If fewer than 2 patients achieve response, the study will be stopped. If 2 or more patients have a radiographic response, an additional 21 patients will be enrolled , for a total accrual of 34 patients.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Multi-center Pharmacodynamics Study of TVB-2640 in KRAS Mutant Non-small Cell Lung Carcinomas
Actual Study Start Date : September 11, 2019
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TVB-2640
Patients will be administered TVB-2640 100mg/m2 orally once a day for 8 weeks.
Drug: TVB-2640
TVB-2640 will be administered 100mg/m2 orally once a day for 8 weeks.




Primary Outcome Measures :
  1. Disease control rate of TVB-2640 [ Time Frame: every 8 weeks through study completion, an average of 1 year ]
    Determine Disease control rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.

  2. Response rate of TVB-2640 [ Time Frame: every 8 weeks through study completion, an average of 1 year ]
    Determine response rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.


Secondary Outcome Measures :
  1. Safety profile of TVB-2640 [ Time Frame: Pretreatment and four weeks of treatment. ]
    Secondary endpoints are 11C-acetate tumor uptake pretreatment and at four weeks of treatment and plasma lipidomics pretreatment and at four weeks of treatment.

  2. Establish the predictive value of 11C-acetate PET [ Time Frame: Pretreatment and four weeks of treatment. ]
    To establish the predictive value of 11C-acetate PET pretreatment and post-treatment tumor uptake for disease control rate and response rate

  3. Mean change in fasting plasma lipidomics [ Time Frame: Pretreatment and four weeks of treatment. ]
    Blood samples for fasting plasma lipidomics will be collected at baseline and four weeks of treatment.

  4. Mean change in sebaceous secretion of fatty acids [ Time Frame: Pretreatment and four weeks of treatment. ]
    Sebutabe collection of sebaceous secretion of fatty acids will be performed at baseline and four weeks of treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  1. Metastatic or advanced stage, histologically or cytologically confirmed NSCLC and molecular identification of oncogenic KRAS mutation.

    • KRAS mutant NSCLC must be refractory, relapsed, and/or intolerant (including contraindications to) of combination platinum-doublet chemotherapy and immune checkpoint inhibitor therapy
    • 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.
  2. 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.
  3. Patient has evidence of disease progression on most recent line of therapy.
  4. Patient has measurable disease by RECIST v1.1 (Eisenhauer, 2009).
  5. Age ≥ 18 years.
  6. ECOG performance status of 0 or 1.
  7. Predicted life expectancy of >3 months.
  8. 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
    • LVEF >50%
    • QTcF <470msec
  9. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

    • A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

      • Has not undergone a hysterectomy or bilateral oophorectomy; or
      • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  10. No significant ischemic heart disease or myocardial infarction within 6 months of first dose of TVB-2640 and with current adequate cardiac function as in 3.1.8.
  11. Ability to understand and the willingness to sign a written informed consent.

Exclusion:

  1. 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.
  2. 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.
  3. Patients who require use of strong CYP3A4/5 agonists or inhibitors during study participation.
  4. 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.
  5. 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.
  6. If female, patient is pregnant or breast-feeding.
  7. Patient has evidence of a serious active infection-infection requiring treatment with intravenous antibiotics.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. Patient has a known allergy or hypersensitivity to components of TVB-2640.
  13. Patient has a prior history of hypersensitivity, drug/radiation-induced, or other immune-mediated pneumonitis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03808558


Contacts
Layout table for location contacts
Contact: Jeffery Wilson 214-648-7097 Jeffery.Wilson@utsouthwestern.edu
Contact: David Gerber, MD david.gerber@utsouthwestern.edu

Locations
Layout table for location information
United States, Ohio
University of Cincinnati Not yet recruiting
Cincinnati, Ohio, United States, 45229
Contact: Muhammad Riaz, MD    513-584-7698    Riazmk@ucmail.uc.edu   
Contact: Christine Vollmer, MBA    mccordce@ucmail.uc.edu    mccordce@ucmail.uc.edu   
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-9179
Contact: David Gerber, MD    214-648-4180    David.Gerber@utsouthwestern.edu   
Principal Investigator: David Gerber, MD         
Sponsors and Collaborators
David E Gerber
Sagimet Biosciences Inc.
Cancer Prevention Research Institute of Texas
Investigators
Layout table for investigator information
Principal Investigator: David Gerber, MD Professor
Layout table for additonal information
Responsible Party: David E Gerber, PROFESSOR - Internal Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03808558    
Other Study ID Numbers: STU 022017-058
First Posted: January 17, 2019    Key Record Dates
Last Update Posted: February 21, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms