This is a prospective one arm, single center phase 2 trial of TVB-2640 in KRaS mutant nSCLC
patients. 12 patients will be treated with a minimum of 1 cycle of TVB-2640 therapy over 8
weeks. 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,
CTCaev4.03 toxicities, plasma lipid levels and 11C-acetate PeT tumor imaging.
Primary endpoints are ReCiST v1.1 best response and response duration and nCi CTCaev4.1
toxicity profile over eight weeks. Secondary endpoints are 11C-acetate tumor uptake
pretreatment and at four weeks of treatment and plasma lipidomics pretreatment and at four
weeks of treatment.
1. Histologically or cytologically confirmed metastatic or advanced-stage KRAS mutant
NSCLC that is refractory, relapsed, and intolerant of combination chemotherapy and
subsequential immune checkpoint therapy.
2. Patient has progressive disease.
3. Patient has measurable disease by RECIST v1.1 (Eisenhauer, 2009).
4. Age ≥ 18 years.
5. ECOG performance status of 0 or 1.
6. Predicted life expectancy of >3 months.
7. Adequate organ and marrow function as defined below:
1. - absolute neutrophil count ≥ 1,500/mcL 2. - platelets ≥ 100,000/mcL 3. - total
bilirubin <2X institutional upper limit of normal 4. - AST and ALT ≤5X institutional upper
limit of normal 5. - creatinine <1.5X institutional upper limit of normal 6. -LVEF >50% 7.
8. 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.
1. 188.8.131.52 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:
9. Has not undergone a hysterectomy or bilateral oophorectomy; or 10. 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).
11. 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 3.1.7.
12. Ability to understand and the willingness to sign a written informed consent.
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 heart failure,
severe hypokalemia with potassium less than 3mM/L, family history of long QT syndrome
or require use during study participation of concomitant medications known to prolong
QT/QTc interval—see http://crediblemeds.org/everyone/
3. Patients who require use of strong CYP3A4/5 agonists or inhibitors during study
4. Patient has uncontrolled or severe intercurrent medical condition including
uncontrolled brain metastases. Patients with stable brain metastases either treated or
being treated with a stable dose of steroids/anticonvulsants, with no dose change
within 4 weeks before the first dose of TVB-2640, and no anticipated dose change, are
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 4 weeks
and 6 weeks for mitomycin C and nitrosoureas or 5 half-lives of that agent whichever
is shorter before the first dose of TVB-2640. A minimum of 10 days between termination
of the investigational drug and administration of TVB-26740 is required. In addition,
any drug-related toxicity, with the exception of alopecia, should have recovered to
6. If female, patient is pregnant or breast-feeding.
7. Patient has evidence of a serious active infection—infection requiring treatment with
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. Patient has a history of other malignancy treated with curative intent within the
previous 5 years with the exception of adequately treated non-melanoma skin cancer or
carcinoma in situ of the cervix.or breast. Subjects with previous invasive cancers are
eligible if the treatment was completed more than 5 years prior to initiating current
study treatment, and there is no evidence of recurrent disease.
11. Patient has a history of clinically significant abnormality on slit-lamp examination
or other clinically significant ophthalmologic finding, as determined by an
12. Patient has a known allergy or hypersensitivity to components of TVB-2640.