Lung Cancer
Conditions
Brief summary
A Phase 2 open label study to evaluate safety and efficacy of VGT-309 to identify cancer in up to 40 subjects undergoing lung cancer surgery.
Detailed description
A Phase 2, open-label study to evaluate the safety and efficacy of VGT-309, a tumor-targeted, activatable fluorescent imaging agent, to identify cancer in subjects undergoing lung cancer surgery. A total of 40 subjects will be enrolled to ensure at least 38 evaluable subjects with the option to expand enrollment by protocol amendment if deemed necessary to meet primary and/or secondary objectives. Following agreement with and signing of the informed consent, subjects will undergo screening measurements for the study. Assessments include the following, unless they have been done within 4 weeks prior to the anticipated dosing: 1. Medical, surgical and medication history. 2. Complete physical exam, including vital signs and weight. 3. Standard pre-operative chemistry, hematology, coagulation and urinalysis clinical laboratory studies. 4. 12-lead ECG. 5. Serum pregnancy test for females of child-bearing potential. Following clearance of all enrollment criteria, each subject will receive an IV administration of 0.32 mg/kg VGT-309 at 12-36 hours prior to surgery (refer to section VGT-309 Dosing, below). Upon dosing, subjects will be observed for up to 2 hours and asked about possible treatment emergent adverse events. Subjects will undergo surgical resection as planned and within the time specified following VGT-309 dosing. Measurements of efficacy will be taken during surgery and during the pathological examination of all surgical specimens. Following surgery, subjects will be monitored for safety during their hospitalization. After discharge from the hospital, and approximately 14 days post-surgery, the subjects will be contacted by telephone to assess their well-being. Between 19 to 39 days post-surgery, subjects will either return to the clinic or participate in a telehealth visit for final safety assessments. If there are no adverse events requiring further follow up, subjects will then be released from the study.
Interventions
DRUGVGT-309
VGT-309 is an tumor-targeted, activatable fluorescent imaging agent which will be used with near infrared imaging during surgery to identify tumor.
Sponsors
National Cancer Institute (NCI)
Vergent Bioscience, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All subjects to be dosed at the same dose level. This is open label and no randomization is required.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Be willing and able to sign the informed consent and comply with study procedures. 2. Be between the ages of 18 and 85, inclusive. 3. Be male or female and meet the following conditions: 1. Female participants must be of non-childbearing potential, or, 2. If of childbearing potential be non-pregnant or non-lactating and agree to use highly effective contraception from screening through Day 30. 3. Male participants, if not surgically sterilized, and if engaging in sexual intercourse with a female partner of childbearing potential, must be willing to use highly effective contraception from screening through 30 days post-dose and agree not to donate semen during this waiting period. 4. Highly effective contraception involves the use of a condom for the male, plus one of the following for the female: * Oral, injectable, implantable, intravaginal, or transdermal hormonal contraceptives, or * Intrauterine device or intrauterine hormone-releasing system * NOTE: Participants who abstain from heterosexual intercourse as their usual and preferred lifestyle, will not be required to use contraception as described above. They are required to maintain abstinence from screening through Day 30. 4. Have a lung nodule or mass that might be considered primary lung cancer or lung metastases, whether or not it is biopsy-proven. 5. Be scheduled to undergo standard of care surgical resection for a lung nodule or mass with diagnostic and/or curative intent and meet all pre-operative surgical and anesthesia acceptance criteria. 6. Have acceptable kidney and liver functions at study entry as evidenced by: 1. Alanine Aminotransferase/Aspartate Aminotransferase (ALT/AST) \< 1.5 times the upper limit of normal 2. Serum creatinine \< 1.5 times the upper limit of normal 7. Have an Eastern Cooperative Oncology Group (ECOG) score of 0-2. 8. Meet all standard surgical and general anesthesia requirements. 9. Have not participated in a clinical trial within the last 30 days.
Exclusion criteria
1. They are not a candidate for standard of care surgery based on opinion of the surgeon, anesthesiologist, or other consulting physician. 2. They have a known allergy or reaction to indocyanine green (ICG), other radiographic contrast agent, or any component of VGT-309. 3. Have congenital long QT syndrome or QTcF \> 450ms (males) or \>470ms (females) by history or at Screening ECG. 4. They are prisoners, institutionalized individuals, or are unable to consent for themselves. 5. Have any other co-morbidity or habit that the Investigator believes will interfere with their ability to comply with and complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Significant Event (CSE) | Day of surgery | Identification of the proportion of subjects with at least one CSE as defined by: A. Localization of a Pulmonary Nodule using VGT-309 near-infrared (NIR) Imaging when white light and palpation failed to identify a nodule. B. Synchronous Lesion Identification using VGT-309 NIR Imaging when not identified by white light and palpation. C. Positive Margin Identification with only VGT-309 NIR Imaging when deemed negative by the surgeon by white light and palpation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity | Day of surgery | Sensitivity is defined as the probability that tissue fluoresces intraoperatively when it is cancer as confirmed by histology. Sensitivity = (True Positive)/(True Positive + False Negative) |
| Negative Predictive Value | Day of surgery | Negative predictive value is defined as the probability that a tissue sample does not contain cancer on histologic exam if it does not fluoresce intraoperatively. Negative Predictive Value = (True Negative)/(True Negative + False Negative) |
| Specificity | Day of surgery | Specificity is defined as the probability that tissue does not fluoresce intraoperatively when it is not cancerous as confirmed by histology. Specificity = (True Negative)/(True Negative + False Positive) |
| Positive Predictive Value | Day of surgery | Positive predictive value is defined as the probability that a tissue sample contains cancer on histologic exam if it fluoresces intraoperatively. Positive Predictive Value = (True Positive)/(True Positive + False Positive) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VGT-309 0.32mg/kg One-time dose by IV infusion over 15-20 minutes using a syringe pump between 12-36 hours prior to the start of surgery | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | VGT-309 0.32mg/kg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 27 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Customized Age | 66 years STANDARD_DEVIATION 10.51 |
| Body Mass Index | 28.62 kg/m^2 STANDARD_DEVIATION 9.349 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 165.33 cm STANDARD_DEVIATION 13.863 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 12 Participants |
| Weight | 77.61 kg STANDARD_DEVIATION 23.658 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 8 / 40 |
Outcome results
Primary
Clinically Significant Event (CSE)
Identification of the proportion of subjects with at least one CSE as defined by: A. Localization of a Pulmonary Nodule using VGT-309 near-infrared (NIR) Imaging when white light and palpation failed to identify a nodule. B. Synchronous Lesion Identification using VGT-309 NIR Imaging when not identified by white light and palpation. C. Positive Margin Identification with only VGT-309 NIR Imaging when deemed negative by the surgeon by white light and palpation.
Time frame: Day of surgery
Population: Efficacy Population: All subjects who received any amount of VGT-309 and had surgery with NIR imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGT-309 0.32mg/kg IV Given 12-36 Hours Prior to Surgery | Clinically Significant Event (CSE) | 0.425 Proportion of subjects |
Comparison: Single arm open-labelp-value: <0.000195% CI: [0.27, 0.591]Exact Binomial Test
Secondary
Negative Predictive Value
Negative predictive value is defined as the probability that a tissue sample does not contain cancer on histologic exam if it does not fluoresce intraoperatively. Negative Predictive Value = (True Negative)/(True Negative + False Negative)
Time frame: Day of surgery
Population: Efficacy Population: All subjects who received any amount of VGT-309 and had surgery with NIR imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGT-309 0.32mg/kg IV Given 12-36 Hours Prior to Surgery | Negative Predictive Value | 0.455 Proportion of lesions |
95% CI: [0.202, 0.733]
Secondary
Positive Predictive Value
Positive predictive value is defined as the probability that a tissue sample contains cancer on histologic exam if it fluoresces intraoperatively. Positive Predictive Value = (True Positive)/(True Positive + False Positive)
Time frame: Day of surgery
Population: Efficacy Population: All subjects who received any amount of VGT-309 and had surgery with NIR imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGT-309 0.32mg/kg IV Given 12-36 Hours Prior to Surgery | Positive Predictive Value | 0.773 Proportion of lesions |
95% CI: [0.65, 0.862]
Secondary
Sensitivity
Sensitivity is defined as the probability that tissue fluoresces intraoperatively when it is cancer as confirmed by histology. Sensitivity = (True Positive)/(True Positive + False Negative)
Time frame: Day of surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGT-309 0.32mg/kg IV Given 12-36 Hours Prior to Surgery | Sensitivity | 0.850 Proportion of lesions |
95% CI: [0.675, 0.939]
Secondary
Specificity
Specificity is defined as the probability that tissue does not fluoresce intraoperatively when it is not cancerous as confirmed by histology. Specificity = (True Negative)/(True Negative + False Positive)
Time frame: Day of surgery
Population: Efficacy Population: All subjects who received any amount of VGT-309 and had surgery with NIR imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGT-309 0.32mg/kg IV Given 12-36 Hours Prior to Surgery | Specificity | 0.333 Proportion of lesions |
95% CI: [0.126, 0.633]