Breast Cancer
Conditions
Keywords
hormone-receptor positive breast cancer, Her2 negative breast cancer, neoadjuvant, everolimus, TRC105, letrozole
Brief summary
This study will test how well a new combination of three drugs (Letrozole, Everolimus, and TRC105) is tolerated and how well it works in Stage 2 and 3 breast cancer when given prior to definitive surgery. Letrozole blocks the estrogen receptor expressed by many breast cancers while everolimus blocks signals that drive cancer cells to grow. TRC105 is an investigational drug that blocks the formation and growth of blood vessels that feed the cancer and promote its growth. The goal of this study is to investigate the safety and efficacy of this multitargeted approach in breast cancer.
Detailed description
In postmenopausal women with hormone receptor-positive and Her2 negative non-metastatic breast cancer, downstaging or the achievement of a complete pathologic remission before definitive surgery has been associated with the lowest risk of recurrence of breast cancer. In order to achieve a better response in these patients in the preoperative setting, this study combines 3 potentially synergistic agents. Letrozole blocks the synthesis of estrogens and, in doing so, deprives the tumor from hormones which drive its growth. Everolimus is a drug that blocks growth factor signaling which is essential for tumor cells to maintain their growth and proliferation. Everolimus has already been shown to work very well in this subtype of breast cancer in the recurrent and metastatic setting. TRC105 is an investigational agent that prevents the formation and growth of new blood vessels that support tumors by providing oxygen and nutrients. The study has 2 components. First the investigators will determine the ideal in terms of tolerance combination of doses of the 3 agents. Once the ideal regimen is determined, more patients will be treated with the investigational combination. During this second stage, the investigators will get a preliminary idea of how effective the investigational therapy is. Further studies will need to be done to confirm the efficacy of the investigational combination.
Interventions
DRUGLetrozole
A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
DRUGEverolimus
The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
DRUGTRC105
The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery.
Sponsors
University of Alabama at Birmingham
Novartis Pharmaceuticals
Tracon Pharmaceuticals Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recent diagnosis of hormone receptor positive and HER2 negative breast cancer. * Stage 2 and 3 hormone receptor positive and HER2 negative breast cancer (stage T2-4 but not inflammatory, N0-2, M0). * Histological grade I, II or III according to the modified Bloom Richardson scale. * No prior treatment specific for breast cancer. * Postmenopausal status as defined by the National Comprehensive Cancer Network. * ECOG performance status \< 2 (Karnofsky \> 60%). * Must have signed study-specific informed consent. * Liver Function Tests \< 2.5 times the upper normal limit (UNL). * ANC ≥ 1,500/mm3, platelets ≥ 100,000/mm3, Hemoglobin ≥ 10g%. * Renal function: serum creatinine \< 1.5 institutional UNL or creatinine clearance \> 40 cc/min.
Exclusion criteria
* Inflammatory breast cancer. * Pre- and peri-menopausal state. * Pregnancy. * Metastatic disease. * HER2 positive breast cancer by immunohistochemistry or FISH. * Triple negative breast cancer (hormone receptor and Her2 negative). * Disease that cannot be followed by imaging studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-limiting Toxicities | 4 weeks | This outcome will report the number of patients who experienced a dose-limiting Toxicity (DLT) in Phase I Cohort 1, Phase I Cohort 2, and Phase I Cohort -1. A DLT was defined as: 1. A grade 3 or 4 non-hematologic toxicity except anorexia, alopecia, nausea (which is not refractory to antiemetics), fatigue, and fever without neutropenia; 2. Failure to recover to baseline (except alopecia) after delaying the next dose by more than 14 days; 3. Grade 3 or 4 neutropenia complicated by fever \>38.5°C or infection, or grade 4 neutropenia of ≥7 days duration; or 4. Grade 4 thrombocytopenia, or grade 3 thrombocytopenia complicated by hemorrhage. The maximum tolerated dose (MTD) is defined as the highest dose at which 0 out of the first 3 or 1 out of a total of 6 patients experience DLT during the first cycle of therapy; this dose level will be the recommended phase 2 dose (RP2D) in the Phase II Group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Pathologic Complete Remission (pCR) | 24 weeks up to time of surgery | The 2-dimensional size of the surgically excised residual tumor was measured and compared to the radiographic size of the tumor at baseline. 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 and reduction in short axis of any pathological lymph nodes to \<10 mm; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| C Max - Letrozole | Day 1 and Day 29 | Maximum serum concentration of Letrozole. |
| Tumor Proliferation Changes | 24 weeks (pretreatment to time of definitive surgery) | This outcome will report the change in tumor cell proliferation. This was measured by the change in the percentage of Ki67 positive cells from pretreatment to surgery (up to 24 weeks): (%Ki67(+) cells pretreatment - %Ki67(+) cells posttreatment)/(%Ki67(+) cells pretreatment) \* 100 Ki67 is a protein found in cells that are dividing. The Ki-67 assessment was performed by the clinical histology laboratory using a validated assay. The results were evaluated by a board-certified pathologist, who estimated the proportion of cancer cells stained for Ki-67. The individual tissue sections were analyzed blindly and at the completion of the assay, results were correlated per case as to changes in Ki-67 with the investigational therapy. |
| T Max - Letrozole | Day 1 | T Max is the time to the maximum serum concentration of a drug in the blood. This outcome will report the T Max of Letrozole at Day 1 in Phase 1 Cohort 1, Phase 1 Cohort 2, and Phase 2. All patients in the trial received the same dose of letrozole. |
| AUC - Letrozole | Day 1 and Day 29 | This outcome will report the area under the serum concentration of letrozole versus time curve (AUC-L). AUC-L is the integral of the concentration of letrozole in the blood as a function of time. AUC-L measures how much letrozole reaches the bloodstream in a period of time after a dose is given. This is useful in dose determination and assessing drug interactions. This outcome was assessed on Day 1 and on Day 29 for Phase I Cohort I, Phase I Cohort 2, and Phase 2. |
| T 1/2 - Letrozole | Day 1 | T ½ is the half-life of a drug in the blood. This is the time it takes for the concentration of the drug in the blood to be reduced by half. This outcome will report the T 1/2 of Letrozole. |
| C Max - Everolimus | Day 1 and Day 29 | Cmax is the maximum serum concentration of a drug in the blood. This outcome will report the Cmax of Everolimus in Phase 1 Cohort 1 and Phase 1 Cohort 2 combined with Phase 2 (since the dose of everolimus was the same in these cohorts) at Day 1 and Day 29. |
| T Max Everolimus | Day 1 | T Max is the time to the maximum serum concentration of a drug in the blood. This outcome will report the T Max of Everolimus in Phase 1 Cohort 1, and combined Phase 1 Cohort 2 and Phase 2 (since patients received the same dose of everolimus) at Day 1. |
| AUC - Everolimus | Day 1 and Day 29 | This outcome will report the area under the serum concentration everolimus of versus the time curve (AUC-E). AUC-E is the integral of the concentration of everolimus in the blood as a function of time. AUC-E measures how much everolimus reaches the bloodstream in a period of time after a dose is given. This is useful in dose determination and assessing drug interactions. This outcome was assessed on Day 1 and on Day 29 for Phase I Cohort I, and combined Phase I Cohort 2 and Phase 2 (since patients in Phase I cohort 2 and Phase 2 received the same dose of everolimus). |
| T 1/2 - Everolimus | day 1 | T ½ is the half-life of a drug in the blood. This is the time it takes for the concentration of the drug in the blood to be reduced by half. This outcome will report the T 1/2 of Everolimus in Phase 1 Cohort 1 and combined Phase 1 Cohort 2 and Phase 2 at Day 1 (since patients in Phase 1 Cohort 2 and Phase 2 at Day 1 received the same dose of everolimus). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORErica Stringer-Reasor, M.D.
University of Alabama at Birmingham
PRINCIPAL_INVESTIGATORErica Stringer-Reasor, MD
University of Alabama at Birmingham
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase I Cohort 1 Letrozole 2.5 mg PO daily until surgery, everolimus 5 mg PO daily for 24 weeks, and TRC105 15 mg/kg IV q 2 weeks for 24 weeks
Letrozole: A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
Everolimus: The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
TRC105: The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery. | 6 |
| Phase I Cohort 2 Letrozole 2.5 mg PO daily until surgery, everolimus 10 mg PO daily for 24 weeks, and TRC105 15 mg/kg IV q 2 weeks for 24 weeks
Letrozole: A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
Everolimus: The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
TRC105: The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery. | 4 |
| Phase I Cohort -1 Letrozole 2.5 mg PO daily until surgery, everolimus 5 mg PO daily for 24 weeks, and TRC105 10 mg/kg IV q 2 weeks for 24 weeks
Letrozole: A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
Everolimus: The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
TRC105: The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery. | 0 |
| Phase II Letrozole 2.5 mg PO daily until surgery, everolimus 5 or 10 mg PO daily for 24 weeks, and TRC105 15 or 10 mg/kg IV q 2 weeks for 24 weeks. Dose and regimen to be determined based on data from the phase I component.
Letrozole: A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
Everolimus: The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
TRC105: The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery. | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | Phase I Cohort 1 | Phase I Cohort 2 | Phase I Cohort -1 | Phase II | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 4 Participants | 0 Participants | 3 Participants | 13 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 4 Participants | 0 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 0 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 | 0 / 0 | 0 / 5 |
| other Total, other adverse events | 6 / 6 | 4 / 4 | 0 / 0 | 0 / 5 |
| serious Total, serious adverse events | 1 / 6 | 0 / 4 | 0 / 0 | 0 / 5 |
Outcome results
Primary
Number of Participants Who Experienced Dose-limiting Toxicities
This outcome will report the number of patients who experienced a dose-limiting Toxicity (DLT) in Phase I Cohort 1, Phase I Cohort 2, and Phase I Cohort -1. A DLT was defined as: 1. A grade 3 or 4 non-hematologic toxicity except anorexia, alopecia, nausea (which is not refractory to antiemetics), fatigue, and fever without neutropenia; 2. Failure to recover to baseline (except alopecia) after delaying the next dose by more than 14 days; 3. Grade 3 or 4 neutropenia complicated by fever \>38.5°C or infection, or grade 4 neutropenia of ≥7 days duration; or 4. Grade 4 thrombocytopenia, or grade 3 thrombocytopenia complicated by hemorrhage. The maximum tolerated dose (MTD) is defined as the highest dose at which 0 out of the first 3 or 1 out of a total of 6 patients experience DLT during the first cycle of therapy; this dose level will be the recommended phase 2 dose (RP2D) in the Phase II Group.
Time frame: 4 weeks
Population: There were no patients enrolled in the phase 1 cohort -1 portion of the protocol due to lack of toxicities in phase 1 cohort 1 and 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Cohort 2 | Number of Participants Who Experienced Dose-limiting Toxicities | 0 participants |
| Phase I Cohort 1 | Number of Participants Who Experienced Dose-limiting Toxicities | 1 participants |
Secondary
AUC - Everolimus
This outcome will report the area under the serum concentration everolimus of versus the time curve (AUC-E). AUC-E is the integral of the concentration of everolimus in the blood as a function of time. AUC-E measures how much everolimus reaches the bloodstream in a period of time after a dose is given. This is useful in dose determination and assessing drug interactions. This outcome was assessed on Day 1 and on Day 29 for Phase I Cohort I, and combined Phase I Cohort 2 and Phase 2 (since patients in Phase I cohort 2 and Phase 2 received the same dose of everolimus).
Time frame: Day 1 and Day 29
Population: Phase I Cohort I, and combined Phase I Cohort 2 and Phase 2 (since patients in Phase I cohort 2 and Phase 2 received the same dose of everolimus)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I Cohort 2 | AUC - Everolimus | Day 1 | 15.4 ng*hrs/mL | Geometric Coefficient of Variation 41.9 |
| Phase I Cohort 2 | AUC - Everolimus | Day 29 | 22.5 ng*hrs/mL | Geometric Coefficient of Variation 39.3 |
| Phase I Cohort 1 | AUC - Everolimus | Day 1 | 20.9 ng*hrs/mL | Geometric Coefficient of Variation 50.4 |
| Phase I Cohort 1 | AUC - Everolimus | Day 29 | 32.1 ng*hrs/mL | Geometric Coefficient of Variation 153 |
Secondary
AUC - Letrozole
This outcome will report the area under the serum concentration of letrozole versus time curve (AUC-L). AUC-L is the integral of the concentration of letrozole in the blood as a function of time. AUC-L measures how much letrozole reaches the bloodstream in a period of time after a dose is given. This is useful in dose determination and assessing drug interactions. This outcome was assessed on Day 1 and on Day 29 for Phase I Cohort I, Phase I Cohort 2, and Phase 2.
Time frame: Day 1 and Day 29
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I Cohort 2 | AUC - Letrozole | Day 1 | 639 ng*hrs/ml | Geometric Coefficient of Variation 34 |
| Phase I Cohort 2 | AUC - Letrozole | Day 29 | 3500 ng*hrs/ml | Geometric Coefficient of Variation 41.7 |
| Phase I Cohort 1 | AUC - Letrozole | Day 1 | 532 ng*hrs/ml | Geometric Coefficient of Variation 17.1 |
| Phase I Cohort 1 | AUC - Letrozole | Day 29 | 2500 ng*hrs/ml | Geometric Coefficient of Variation 205 |
| Phase I Cohort -1 | AUC - Letrozole | Day 1 | 408 ng*hrs/ml | Geometric Coefficient of Variation 28.5 |
| Phase I Cohort -1 | AUC - Letrozole | Day 29 | 1400 ng*hrs/ml | Geometric Coefficient of Variation 195 |
Secondary
C Max - Everolimus
Cmax is the maximum serum concentration of a drug in the blood. This outcome will report the Cmax of Everolimus in Phase 1 Cohort 1 and Phase 1 Cohort 2 combined with Phase 2 (since the dose of everolimus was the same in these cohorts) at Day 1 and Day 29.
Time frame: Day 1 and Day 29
Population: Phase 1 Cohort 1 and Phase 1 Cohort 2 combined with Phase 2 (since the dose of everolimus was the same in these cohorts) at Day 1 and Day 29.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I Cohort 2 | C Max - Everolimus | day 1 | 1.56 ng/mL | Geometric Coefficient of Variation 51.5 |
| Phase I Cohort 2 | C Max - Everolimus | day 29 | 2.63 ng/mL | Geometric Coefficient of Variation 27.9 |
| Phase I Cohort 1 | C Max - Everolimus | day 1 | 3.7 ng/mL | Geometric Coefficient of Variation 55.5 |
| Phase I Cohort 1 | C Max - Everolimus | day 29 | 5.38 ng/mL | Geometric Coefficient of Variation 86.7 |
Secondary
C Max - Letrozole
Maximum serum concentration of Letrozole.
Time frame: Day 1 and Day 29
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I Cohort 2 | C Max - Letrozole | Day 1 | 45.3 ng/ml | Geometric Coefficient of Variation 31.5 |
| Phase I Cohort 2 | C Max - Letrozole | Day 29 | 211 ng/ml | Geometric Coefficient of Variation 32.7 |
| Phase I Cohort 1 | C Max - Letrozole | Day 1 | 41.2 ng/ml | Geometric Coefficient of Variation 28.6 |
| Phase I Cohort 1 | C Max - Letrozole | Day 29 | 292 ng/ml | Geometric Coefficient of Variation 53.1 |
| Phase I Cohort -1 | C Max - Letrozole | Day 1 | 33.3 ng/ml | Geometric Coefficient of Variation 43.8 |
| Phase I Cohort -1 | C Max - Letrozole | Day 29 | 168 ng/ml | Geometric Coefficient of Variation 73.5 |
Secondary
Rates of Pathologic Complete Remission (pCR)
The 2-dimensional size of the surgically excised residual tumor was measured and compared to the radiographic size of the tumor at baseline. 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 and reduction in short axis of any pathological lymph nodes to \<10 mm; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 24 weeks up to time of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I Cohort 2 | Rates of Pathologic Complete Remission (pCR) | 0 Participants |
| Phase I Cohort 1 | Rates of Pathologic Complete Remission (pCR) | 0 Participants |
| Phase I Cohort -1 | Rates of Pathologic Complete Remission (pCR) | 0 Participants |
Secondary
T 1/2 - Everolimus
T ½ is the half-life of a drug in the blood. This is the time it takes for the concentration of the drug in the blood to be reduced by half. This outcome will report the T 1/2 of Everolimus in Phase 1 Cohort 1 and combined Phase 1 Cohort 2 and Phase 2 at Day 1 (since patients in Phase 1 Cohort 2 and Phase 2 at Day 1 received the same dose of everolimus).
Time frame: day 1
Population: Phase 1 Cohort 1 and combined Phase 1 Cohort 2 and Phase 2 at Day 1 (since patients in Phase 1 Cohort 2 and Phase 2 at Day 1 received the same dose of everolimus).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase I Cohort 2 | T 1/2 - Everolimus | 13.4 hours | Geometric Coefficient of Variation 1.64 |
| Phase I Cohort 1 | T 1/2 - Everolimus | 11.8 hours | Geometric Coefficient of Variation 7.86 |
Secondary
T 1/2 - Letrozole
T ½ is the half-life of a drug in the blood. This is the time it takes for the concentration of the drug in the blood to be reduced by half. This outcome will report the T 1/2 of Letrozole.
Time frame: Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase I Cohort 2 | T 1/2 - Letrozole | 15.5 Hours | Geometric Coefficient of Variation 4.26 |
| Phase I Cohort 1 | T 1/2 - Letrozole | 24.7 Hours | Geometric Coefficient of Variation 2.34 |
| Phase I Cohort -1 | T 1/2 - Letrozole | 31.7 Hours | Geometric Coefficient of Variation 11.4 |
Secondary
T Max Everolimus
T Max is the time to the maximum serum concentration of a drug in the blood. This outcome will report the T Max of Everolimus in Phase 1 Cohort 1, and combined Phase 1 Cohort 2 and Phase 2 (since patients received the same dose of everolimus) at Day 1.
Time frame: Day 1
Population: Phase 1 Cohort 1, and combined Phase 1 Cohort 2 and Phase 2 (since patients received the same dose of everolimus) at Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I Cohort 2 | T Max Everolimus | 2 hours |
| Phase I Cohort 1 | T Max Everolimus | 1 hours |
Secondary
T Max - Letrozole
T Max is the time to the maximum serum concentration of a drug in the blood. This outcome will report the T Max of Letrozole at Day 1 in Phase 1 Cohort 1, Phase 1 Cohort 2, and Phase 2. All patients in the trial received the same dose of letrozole.
Time frame: Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I Cohort 2 | T Max - Letrozole | 3 Hours |
| Phase I Cohort 1 | T Max - Letrozole | 1.5 Hours |
| Phase I Cohort -1 | T Max - Letrozole | 2 Hours |
Secondary
Tumor Proliferation Changes
This outcome will report the change in tumor cell proliferation. This was measured by the change in the percentage of Ki67 positive cells from pretreatment to surgery (up to 24 weeks): (%Ki67(+) cells pretreatment - %Ki67(+) cells posttreatment)/(%Ki67(+) cells pretreatment) \* 100 Ki67 is a protein found in cells that are dividing. The Ki-67 assessment was performed by the clinical histology laboratory using a validated assay. The results were evaluated by a board-certified pathologist, who estimated the proportion of cancer cells stained for Ki-67. The individual tissue sections were analyzed blindly and at the completion of the assay, results were correlated per case as to changes in Ki-67 with the investigational therapy.
Time frame: 24 weeks (pretreatment to time of definitive surgery)
Population: There were no patients enrolled in Phase 1 Cohort -1 due to the lack of toxicities in Phase 1 Cohort 1 and Phase I Cohort 2. Additionally, one patient in Phase 1 Cohort 1, one patient in Phase 1 cohort 2, and two patients in Phase 2 were not evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I Cohort 2 | Tumor Proliferation Changes | -96.7 percent change in the of Ki67(+) cells |
| Phase I Cohort 1 | Tumor Proliferation Changes | 14 percent change in the of Ki67(+) cells |
| Phase I Cohort -1 | Tumor Proliferation Changes | -77.8 percent change in the of Ki67(+) cells |