KRAS Gene MutationPhase 2NCT03808558

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

A Phase 2 study testing TVB-2640 in people with KRAS Gene Mutation, run by David E Gerber at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: KRAS Gene Mutation
What is being tested?: TVB-2640
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 2 sitesUnited States
Study dates: 11 Sep 2019to 1 Dec 2026
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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).

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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
LVEF >50%
QTcF <470msec
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).
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.
Ability to understand and the willingness to sign a written informed consent.

Who cannot join

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.

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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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

University of Cincinnati
Cincinnati, Ohio, 45267
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-9179

Other trials in United States

About this study

Official title: A Phase 2 Multi-center Pharmacodynamics Study of TVB-2640 in KRAS Mutant Non-small Cell Lung Carcinomas

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.

Read the 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.

Conditions: KRAS Gene Mutation
Being tested: TVB-2640

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03808558
Study group	Role	What they receive
TVB-2640	Experimental	Patients will be administered TVB-2640 100mg/m2 orally once a day for 8 weeks. Receives: Drug: TVB-2640

What is being measured

The primary outcome is the main question the study is designed to answer.

Disease Control Rate of TVB-2640
Determine Disease control rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >=20% increase in the sum of diameters of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: 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. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >=20% increase in the sum of diameters of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: every 8 weeks through study completion, an average of 1 year

Secondary outcomes (4)

Safety Profile of TVB-2640
Secondary endpoints are 11C-acetate tumor uptake pretreatment and at four weeks of treatment and plasma lipidomics pretreatment and at four weeks of treatment.
Measured: Pretreatment and four weeks of treatment.
Establish the Predictive Value of 11C-acetate PET
To establish the predictive value of 11C-acetate PET pretreatment and post-treatment tumor uptake for disease control rate and response rate
Measured: Pretreatment and four weeks of treatment.
Mean Change in Fasting Plasma Lipidomics
Blood samples for fasting plasma lipidomics will be collected at baseline and four weeks of treatment.
Measured: Pretreatment and four weeks of treatment.
Mean Change in Sebaceous Secretion of Fatty Acids
Sebutabe collection of sebaceous secretion of fatty acids will be performed at baseline and four weeks of treatment
Measured: Pretreatment and four weeks of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Sep 20191 Dec 2026

First posted17 Jan 2019
Study start11 Sep 2019
Primary completion3 Apr 2025
Study completion1 Dec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for KRAS Gene MutationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03808558
Sponsor's protocol ID: STU 022017-058
Status last verified: May 2026
First submitted: 24 May 2018
Last updated: 22 May 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2 Multi-center Pharmacodynamics Study of TVB-2640 in KRAS Mutant Non-small Cell Lung Carcinomas
ClinicalTrials.gov ID: NCT03808558
Acronym / sponsor ID: STU 022017-058
Conditions: KRAS Gene Mutation
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 18 participants (actual)
Lead sponsor: David E GerberUniversity, hospital or other
Collaborators: Sagimet Biosciences Inc., Cancer Prevention Research Institute of Texas, Gateway for Cancer Research
Study start: 11 Sep 2019 (actual)
Primary completion: 3 Apr 2025 (actual)
Study completion: 1 Dec 2026 (estimated)
First posted: 17 Jan 2019 (actual)
Results: Posted 22 May 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

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

Key exclusion criteria (13 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

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

Primary outcome

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. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >=20% increase in the sum of diameters of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
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. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >=20% increase in the sum of diameters of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

4 secondary outcomes

Safety Profile of TVB-2640
Time frame: Pretreatment and four weeks of treatment.
Establish the Predictive Value of 11C-acetate PET
Time frame: Pretreatment and four weeks of treatment.
Mean Change in Fasting Plasma Lipidomics
Time frame: Pretreatment and four weeks of treatment.
Mean Change in Sebaceous Secretion of Fatty Acids
Time frame: Pretreatment and four weeks of treatment.

Results and safety

Results posted to the registry on 22 May 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TVB-2640	18	18

Primary outcome: Disease Control Rate of TVB-2640

Time frame: every 8 weeks through study completion, an average of 1 year. Count of participants. Unit: Participants

Measure	TVB-2640 n = 18
Value	16

Primary outcome: Response Rate of TVB-2640

Time frame: every 8 weeks through study completion, an average of 1 year. Count of participants. Unit: Participants

Measure	TVB-2640 n = 18
Partial Disease	9
Stable Disease	7
Unknown Outcome	2

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 4 years, 6 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TVB-2640	18 of 18 (100%)	18 of 18 (100%)	17 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Gerber, MD principal investigator

Professor

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TVB-2640 in people with KRAS Gene Mutation, run by David E Gerber at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Control Rate of TVB-2640 (time frame: every 8 weeks through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03808558.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.