Breast Cancer, Breast Neoplasms
Conditions
Keywords
clinical stage I, II or III, ER postive, HER2 negative
Brief summary
The purpose of this study is to evaluate a new investigational cancer vaccine, P10s-PADRE in combination with standard neoadjuvant chemotherapy and surgery in patients with clinical stage I, II or III estrogen-receptor (ER)-positive, HER2-negative breast cancer.
Detailed description
The purpose of this study is to evaluate an investigational agent, P10s-PADRE, a peptide mimotope-based vaccine, in combination with standard neoadjuvant chemotherapy in patients with clinical stage I, II or III estrogen-receptor (ER)-positive, HER2-negative breast cancer. This is a single-arm, multi-site Phase I/II study designed with the two goals being (1) to evaluate the feasibility of combining vaccination with the P10s-PADRE formulation with neoadjuvant chemotherapy and (2) to determine if the polymerase chain reaction (pCR) rate among ER-positive, HER2-negativebreast-cancer patients treated with the combination is significantly higher than the 8% rate observed among ER-positive breast-cancer subjects in a pooled analysis of seven randomized clinical trials. P10s-PADRE vaccine with MONTANIDE™ ISA 51 VG as adjuvant will be given in combination with neoadjuvant chemotherapy in female patients with clinical stage I, II or III ER-positive, HER2-negative breast cancer. This combined Phase I/II feasibility-and-efficacy study will have three parts. Its first part will be a Phase I evaluation of the safety, tolerability, and feasibility of eliciting adequate IgG response with P10s-PADRE when administered in combination with SoC neoadjuvant chemotherapy. The study's second and third parts will respectively constitute Stages 1 and 2 of the Phase II primary-efficacy evaluation of Chemovax using a Simon optimal two-stage design To evaluate the feasibility of eliciting adequate immune response with P10s-PADRE when it is administered in combination with neoadjuvant chemotherapy, we will sequentially evaluate different schedules of vaccination relative to chemotherapy, and stop evaluating as soon as we have identified a feasible schedule. To this end, we have defined five different Chemovax schedules, and named them A, B, C, D, and E;
Interventions
BIOLOGICALP10s-PADRE/ MONTANIDE™ ISA 51 VG
Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions concurrent with chemotherapy.
DRUGDoxorubicin
Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.
DRUGCyclophosphamide
Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles.
DRUGDocetaxel
Doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) will be administered concurrently every three weeks for four cycles followed by docetaxel (75 mg/m2) every three weeks for four cycles. If docetaxel is not tolerated, paclitaxel (175mg/m2) may be used in its place.
Sponsors
University of Arkansas
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This combined Phase I/II feasibility-and-efficacy study will have three parts. Part 1 will be a Phase I evaluation of the safety, tolerability, and feasibility of the Chemovax to assess the timing of vaccination relative to chemotherapy. Five different Chemovax schedules (Schedule A, B, C, D, and E) will be sequentially evaluated. Once such a feasible schedule is identified, the study will proceed with its second and third parts. Part 2 (primary efficacy) and Part 3 (expanded efficacy) will respectively constitute Stages 1 and 2 of the Phase II primary-efficacy evaluation of Chemovax using a Simon optimal two-stage design.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females of all races with clinical stage I, II, or III ER-positive, HER2 negative breast cancer who will undergo SoC neoadjuvant treatment. * Age 18 years and older. * ECOG Performance Status 0 or 1. * White blood cell (WBC) count ≥ 3,000/mm3 within 3 weeks prior to registration. * Platelet count ≥ 100,000/mm3 within 3 weeks prior to registration. * Bilirubin ≤ 2 x institutional upper limit (IUL) of normal obtained within 3 weeks prior to registration. * Serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase test (AST) ≤ 2 x IUL of normal obtained within 3 weeks prior to registration. * Serum glutamic-pyruvic transaminase (SGPT) or alanine aminotransferase test (ALT) ≤ 2 x IUL of normal obtained within 3 weeks prior to registration. * Serum creatinine ≤ 1.8 mg/dL obtained within 3 weeks prior to registration. * Must sign an informed consent document approved by the UAMS IRB.
Exclusion criteria
* ER-negative, HER2-positive, inflammatory, metastatic, stage IV or recurrent breast cancer * Active infection requiring treatment with antibiotics. * Existing diagnosis or history of organic brain syndrome that might preclude participation in the full protocol. * Existing diagnosis or history of significant impairment of basal cognitive function that might preclude participation in the full protocol. * Other current malignancies. Subjects with prior history at any time of any in situ cancer, including lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark I melanoma in situ or basal or squamous skin cancer are eligible, provided they are disease-free at the time of registration. Subjects with other malignancies are eligible if they have been continuously disease free for ≥ 5 years prior to the time of registration. * Active autoimmune disorders or conditions of immunosuppression; Existing diagnosis or history of autoimmune disorders or conditions of immunosuppression that have been in remission for less than 6 months * Treatment with corticosteroids, including oral steroids (i.e. prednisone, dexamethasone \[except when used as an antiemetic in SoC therapy\]), continuous use of topical steroid creams or ointments or any steroid-containing inhalers. Subjects who discontinue the use of these classes of medication for at least 6 weeks prior to registration are eligible if, in the judgment of the treating physician, the subject is not likely to require these classes of drugs during the treatment period. Replacement doses of steroids for subjects with adrenal insufficiency are allowed. * Pregnancy or breastfeeding (due to the unknown effects of peptide/mimotope vaccines on a fetus or infant). Women of childbearing potential must have a negative urine pregnancy test within 72 hours prior to starting week 1 and must be counseled to use an accepted and effective method of contraception (including abstinence) while on treatment and for a period of 18 months after completing or discontinuing treatment. Accepted methods of contraception include tubal ligation, oral contraceptives, barrier methods, IUDs, and abstinence. * Any other significant medical or psychiatric conditions, which, in the opinion of the enrolling investigator, may interfere with consent or compliance of the treatment regimen. * Enrollment in any other clinical trial using investigational drug products or devices prior to first post-surgery study lab. Concurrent enrollment in observational studies is allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25) | Number of participants with sufficiently high anti-P10s immunoglobulin-G response Feasibility will be evaluated in terms of 1. Generation of a sufficiently high anti-P10s immunoglobulin-G response 2. Safety and tolerability of the combination of vaccine and chemotherapy |
| Determine the pCR Rate | At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25) | The patient-level primary outcome for this objective is pathological Complete Response (pCR), which is binary yes/no, and the study-level endpoint for this outcome is the rate of pCR, i.e. the percentage of patients that achieved pCR=yes. The patient is assessed at the time of surgery for whether they achieved pCR=yes. They have to do the surgery in order to obtain the tissue samples on which they do their pCR assessment. Pathological Complete Response is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0N0 or ypTisN0 in the AJCC staging system for staging solid tumors in the neoadjuvant setting that was described in a 2014 FDA Guidance for Industry). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| P10s-MAP-Reactive Immunoglobulin Titers | Week 1 through Week 70 | The anti-P10s binding level was measured via ELISA method after incubation with a subject's serum or plasma sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. |
| Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Week 1 through Week 70 | Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, CD16 was not assessable. |
| Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Week 1 through Week 70 | Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, CD69 was not assessable. |
| Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Week 1 through Week 70 | Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, NKp46 was not assessable. |
Countries
United States
Participant flow
Recruitment details
Potential subjects were recruited from the Winthrop P Rockefeller Cancer Institute on the University of Arkansas for Medical Sciences campus and clinics at Highlands Oncology Group.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 - Chemovax Schedule A Feasibility - Chemovax schedule A: Subjects will receive the first cycle of chemotherapy along with the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 1, the subsequent two injections of the vaccine one week apart (week 2 and 3), second cycle of chemotherapy on week 4, and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22).
Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period. | 5 |
| Part 1 - Chemovax Schedule B Feasibility - Chemovax Schedule B: Subjects will receive the first cycle of chemotherapy on week 1, the first injection of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine on week 2, the subsequent two injections of the vaccine one week apart (week 3 and 4), second cycle of chemotherapy on week 4 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22).
Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period. | 5 |
| Part 1 - Chemovax Schedule C Feasibility - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).
Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period. | 5 |
| Part 1 - Chemovax Schedule D Feasibility - Chemovax Schedule D: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 2 (along with second vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 5,8,11,14,17,20,23).
Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period. | 5 |
| Part 1 - Chemovax Schedule E Feasibility - Chemovax Schedule E: Subjects will receive the first injection of vaccine on week 1, the subsequent two injections of the P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine one week apart (week 2 and 3), the first cycle of chemotherapy on week 3 (along with third vaccine injection) and subsequent cycles of chemotherapy every 21 days (week 6,9,12,15,18,21,24).
Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period. | 5 |
| Part 2 - Chemovax Schedule C Primary Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25).
Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period. | 19 |
| Part 3 - Chemovax Schedule C Expanded Efficacy - Chemovax Schedule C: Subjects will receive three weekly injections of P10s-PADRE/MONTANIDE™ ISA 51 VG vaccine (week 1,2,3), then first cycle of chemotherapy (week 4), and subsequent cycles of chemotherapy every 21 days (week 7,10,13,16,19,22,25)..
Chemovax - P10s-PADRE/ MONTANIDE™ ISA 51 VG + Doxorubicin + Cyclophosphamide + Docetaxel (or Paclitaxel): Eligible subjects will be enrolled and immunized by SC administration of P10s-PADRE vaccine on each of 3 separate occasions over a three-week period. | 14 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 3 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Part 1 - Chemovax Schedule C | Part 1 - Chemovax Schedule D | Part 1 - Chemovax Schedule E | Part 1 - Chemovax Schedule A | Part 1 - Chemovax Schedule B | Part 2 - Chemovax Schedule C | Part 3 - Chemovax Schedule C | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 17 Participants | 13 Participants | 49 Participants |
| Age, Continuous | 57.6 years STANDARD_DEVIATION 11.69 | 54.8 years STANDARD_DEVIATION 15.42 | 43.4 years STANDARD_DEVIATION 15.24 | 59 years STANDARD_DEVIATION 12.37 | 53 years STANDARD_DEVIATION 10.2 | 52.58 years STANDARD_DEVIATION 10.73 | 46.86 years STANDARD_DEVIATION 10.73 | 50.15 years STANDARD_DEVIATION 10.94 |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage IA | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage IB | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage II | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 5 Participants |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage IIA | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 2 Participants | 11 Participants |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage IIB | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants | 4 Participants | 17 Participants |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage III | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 6 Participants |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage IIIA | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage IIIB | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 8 Participants |
| American Joint Committee on Cancer (AJCC) Tumor Staging Stage not reported/given | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 Fully active, able to carry on all pre-disease | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 18 Participants | 13 Participants | 53 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 Restricted in physically strenuous activity but ambulatory and able to carry out work | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants | 6 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 9 Participants | 6 Participants | 40 Participants |
| Pre-Treatment Tumor Size | 4.82 centimeters STANDARD_DEVIATION 2.03 | 3.76 centimeters STANDARD_DEVIATION 2.56 | 1.96 centimeters STANDARD_DEVIATION 0.82 | 2.9 centimeters STANDARD_DEVIATION 0.84 | 4.06 centimeters STANDARD_DEVIATION 1.44 | 4.13 centimeters STANDARD_DEVIATION 2.67 | 5.43 centimeters STANDARD_DEVIATION 2.19 | 4.03 centimeters STANDARD_DEVIATION 2.38 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 5 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 3 Participants | 14 Participants | 8 Participants | 45 Participants |
| Region of Enrollment United States Central Arkansas at University of Arkansas for Medical Sciences | 2 Participants | 1 Participants | 0 Participants | 5 Participants | 5 Participants | 10 Participants | 14 Participants | 37 Participants |
| Region of Enrollment United States Northwest Arkansas at Highlands Oncology Group | 3 Participants | 4 Participants | 5 Participants | 0 Participants | 0 Participants | 9 Participants | 0 Participants | 21 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 19 Participants | 14 Participants | 58 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumor Grade Grade I | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 6 Participants |
| Tumor Grade Grade II | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 4 Participants | 9 Participants | 4 Participants | 26 Participants |
| Tumor Grade Grade III | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 8 Participants | 6 Participants | 25 Participants |
| Tumor Grade Grade X (Unknown) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Tumor Type Luminal A | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 12 Participants |
| Tumor Type Luminal B | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 13 Participants |
| Tumor Type Not collected | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 19 Participants | 14 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 1 / 33 |
| other Total, other adverse events | 5 / 5 | 5 / 5 | 5 / 5 | 5 / 5 | 5 / 5 | 33 / 33 |
| serious Total, serious adverse events | 4 / 5 | 4 / 5 | 3 / 5 | 1 / 5 | 3 / 5 | 19 / 33 |
Outcome results
Primary
Determine the pCR Rate
The patient-level primary outcome for this objective is pathological Complete Response (pCR), which is binary yes/no, and the study-level endpoint for this outcome is the rate of pCR, i.e. the percentage of patients that achieved pCR=yes. The patient is assessed at the time of surgery for whether they achieved pCR=yes. They have to do the surgery in order to obtain the tissue samples on which they do their pCR assessment. Pathological Complete Response is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0N0 or ypTisN0 in the AJCC staging system for staging solid tumors in the neoadjuvant setting that was described in a 2014 FDA Guidance for Industry).
Time frame: At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)
Population: Clinical Response was determined for participants in Part 2 and 3. Part 2 Chemovax Schedule C was Stage 1 of the Simon 2-stage design. Stage 1's efficacy decision was a rule-based decision. If Stage 1 had 2 or more pCRs, then we could open up Stage 2 and start enrolling patients on it. Part 3 Chemovax Schedule C was Stage 2 of the Simon 2-stage design. It was supposed to enroll 22 subjects, but it had enrolled only 14 subjects by the time the study was closed to enrollment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - Chemovax Schedule A | Determine the pCR Rate | 0 Participants |
| Part 1 - Chemovax Schedule B | Determine the pCR Rate | 0 Participants |
| Part 1 - Chemovax Schedule C | Determine the pCR Rate | 0 Participants |
| Part 1 - Chemovax Schedule D | Determine the pCR Rate | 0 Participants |
| Part 1 - Chemovax Schedule E | Determine the pCR Rate | 0 Participants |
| Part 2 - Chemovax Schedule C | Determine the pCR Rate | 3 Participants |
| Part 3 - Chemovax Schedule C | Determine the pCR Rate | 1 Participants |
Primary
Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently.
Number of participants with sufficiently high anti-P10s immunoglobulin-G response Feasibility will be evaluated in terms of 1. Generation of a sufficiently high anti-P10s immunoglobulin-G response 2. Safety and tolerability of the combination of vaccine and chemotherapy
Time frame: At the time of definitive surgery (4-8 weeks after chemo, which is between Week 22 and Week 25)
Population: This was defined as a \>4-fold increase in a subject's anti-P10s-MAP IgG titer at Week 7 or later (at least 4 weeks after the 3rd immunization) relative to her pre-immune titer. For 1 participant, the Week 7 antibody titer was NA.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - Chemovax Schedule A | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Less than 4-fold increase | 2 Participants |
| Part 1 - Chemovax Schedule A | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Greater than or equal to 4-fold increase | 3 Participants |
| Part 1 - Chemovax Schedule B | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Greater than or equal to 4-fold increase | 2 Participants |
| Part 1 - Chemovax Schedule B | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Less than 4-fold increase | 3 Participants |
| Part 1 - Chemovax Schedule C | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Less than 4-fold increase | 1 Participants |
| Part 1 - Chemovax Schedule C | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Greater than or equal to 4-fold increase | 4 Participants |
| Part 1 - Chemovax Schedule D | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Greater than or equal to 4-fold increase | 2 Participants |
| Part 1 - Chemovax Schedule D | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Less than 4-fold increase | 3 Participants |
| Part 1 - Chemovax Schedule E | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Greater than or equal to 4-fold increase | 4 Participants |
| Part 1 - Chemovax Schedule E | Identify a Feasible Schedule of Vaccination Relative to SoC Neoadjuvant Chemotherapy When the Chemovax Are Administered Concurrently. | Less than 4-fold increase | 1 Participants |
Secondary
Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16
Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, CD16 was not assessable.
Time frame: Week 1 through Week 70
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Chemovax Schedule A | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Pre-Immune CD16 | 26065 Median Fluorescence Intensity (MFI) | Standard Deviation 7976.46 |
| Part 1 - Chemovax Schedule A | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Post-Immune CD16 | 19745.4 Median Fluorescence Intensity (MFI) | Standard Deviation 5182.72 |
| Part 1 - Chemovax Schedule B | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Pre-Immune CD16 | 26580 Median Fluorescence Intensity (MFI) | Standard Deviation 2261.51 |
| Part 1 - Chemovax Schedule B | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Post-Immune CD16 | 20993.4 Median Fluorescence Intensity (MFI) | Standard Deviation 7061.48 |
| Part 1 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Pre-Immune CD16 | 25171.8 Median Fluorescence Intensity (MFI) | Standard Deviation 6493 |
| Part 1 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Post-Immune CD16 | 27998.6 Median Fluorescence Intensity (MFI) | Standard Deviation 10142.41 |
| Part 1 - Chemovax Schedule D | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Pre-Immune CD16 | 28546 Median Fluorescence Intensity (MFI) | Standard Deviation 7197.16 |
| Part 1 - Chemovax Schedule D | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Post-Immune CD16 | 22959.8 Median Fluorescence Intensity (MFI) | Standard Deviation 6020.06 |
| Part 1 - Chemovax Schedule E | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Pre-Immune CD16 | 24897 Median Fluorescence Intensity (MFI) | Standard Deviation 5334.72 |
| Part 1 - Chemovax Schedule E | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Post-Immune CD16 | 25711.75 Median Fluorescence Intensity (MFI) | Standard Deviation 20572.69 |
| Part 2 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Pre-Immune CD16 | 67445.83 Median Fluorescence Intensity (MFI) | Standard Deviation 31389.28 |
| Part 2 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Post-Immune CD16 | 62323.05 Median Fluorescence Intensity (MFI) | Standard Deviation 24021.75 |
| Part 3 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Pre-Immune CD16 | 68619.59 Median Fluorescence Intensity (MFI) | Standard Deviation 27944.66 |
| Part 3 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD16 | Post-Immune CD16 | 65410.12 Median Fluorescence Intensity (MFI) | Standard Deviation 24645.52 |
Secondary
Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69
Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, CD69 was not assessable.
Time frame: Week 1 through Week 70
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Chemovax Schedule A | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Pre-Immune CD69 | 268.2 Median Fluorescence Intensity (MFI) | Standard Deviation 50.08 |
| Part 1 - Chemovax Schedule A | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Post-Immune CD69 | 307 Median Fluorescence Intensity (MFI) | Standard Deviation 72.29 |
| Part 1 - Chemovax Schedule B | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Pre-Immune CD69 | 300.8 Median Fluorescence Intensity (MFI) | Standard Deviation 88.02 |
| Part 1 - Chemovax Schedule B | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Post-Immune CD69 | 329.6 Median Fluorescence Intensity (MFI) | Standard Deviation 26.23 |
| Part 1 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Pre-Immune CD69 | 291.4 Median Fluorescence Intensity (MFI) | Standard Deviation 38.55 |
| Part 1 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Post-Immune CD69 | 275 Median Fluorescence Intensity (MFI) | Standard Deviation 25.25 |
| Part 1 - Chemovax Schedule D | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Pre-Immune CD69 | 294.6 Median Fluorescence Intensity (MFI) | Standard Deviation 57.27 |
| Part 1 - Chemovax Schedule D | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Post-Immune CD69 | 278.4 Median Fluorescence Intensity (MFI) | Standard Deviation 27.87 |
| Part 1 - Chemovax Schedule E | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Pre-Immune CD69 | 296.25 Median Fluorescence Intensity (MFI) | Standard Deviation 34.37 |
| Part 1 - Chemovax Schedule E | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Post-Immune CD69 | 311.25 Median Fluorescence Intensity (MFI) | Standard Deviation 16.76 |
| Part 2 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Pre-Immune CD69 | 428 Median Fluorescence Intensity (MFI) | Standard Deviation 133 |
| Part 2 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Post-Immune CD69 | 489.44 Median Fluorescence Intensity (MFI) | Standard Deviation 139.9 |
| Part 3 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Pre-Immune CD69 | 445.5 Median Fluorescence Intensity (MFI) | Standard Deviation 169.17 |
| Part 3 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune CD69 | Post-Immune CD69 | 505.97 Median Fluorescence Intensity (MFI) | Standard Deviation 161.11 |
Secondary
Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46
Activated-NK-cell profiles will be determined via flow cytometry as the expression levels of different activation markers on NK cells in the subject's blood sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group. For some participants, NKp46 was not assessable.
Time frame: Week 1 through Week 70
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Chemovax Schedule A | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Pre-Immune NKp46 | 685.2 Median Fluorescence Intensity (MFI) | Standard Deviation 390.469 |
| Part 1 - Chemovax Schedule A | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Post-Immune NKp46 | 1391 Median Fluorescence Intensity (MFI) | Standard Deviation 489.819 |
| Part 1 - Chemovax Schedule B | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Pre-Immune NKp46 | 590.4 Median Fluorescence Intensity (MFI) | Standard Deviation 204.147 |
| Part 1 - Chemovax Schedule B | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Post-Immune NKp46 | 1115.6 Median Fluorescence Intensity (MFI) | Standard Deviation 485.348 |
| Part 1 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Pre-Immune NKp46 | 724.2 Median Fluorescence Intensity (MFI) | Standard Deviation 422.436 |
| Part 1 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Post-Immune NKp46 | 1084.2 Median Fluorescence Intensity (MFI) | Standard Deviation 930.867 |
| Part 1 - Chemovax Schedule D | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Pre-Immune NKp46 | 794.2 Median Fluorescence Intensity (MFI) | Standard Deviation 355.618 |
| Part 1 - Chemovax Schedule D | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Post-Immune NKp46 | 1168.2 Median Fluorescence Intensity (MFI) | Standard Deviation 324.282 |
| Part 1 - Chemovax Schedule E | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Pre-Immune NKp46 | 744.25 Median Fluorescence Intensity (MFI) | Standard Deviation 251.998 |
| Part 1 - Chemovax Schedule E | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Post-Immune NKp46 | 1505.5 Median Fluorescence Intensity (MFI) | Standard Deviation 1031.69 |
| Part 2 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Pre-Immune NKp46 | 1360.33 Median Fluorescence Intensity (MFI) | Standard Deviation 638.97 |
| Part 2 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Post-Immune NKp46 | 1412.13 Median Fluorescence Intensity (MFI) | Standard Deviation 645.68 |
| Part 3 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Pre-Immune NKp46 | 1650.08 Median Fluorescence Intensity (MFI) | Standard Deviation 878.64 |
| Part 3 - Chemovax Schedule C | Activation Profiles of NK Cells: Pre-Immune and Post-Immune NKp46 | Post-Immune NKp46 | 1813.56 Median Fluorescence Intensity (MFI) | Standard Deviation 879.38 |
Secondary
P10s-MAP-Reactive Immunoglobulin Titers
The anti-P10s binding level was measured via ELISA method after incubation with a subject's serum or plasma sample. Data was collected at multiple timepoints throughout the study. Values were averaged for each group.
Time frame: Week 1 through Week 70
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - Chemovax Schedule A | P10s-MAP-Reactive Immunoglobulin Titers | 10.72 titers | Standard Deviation 14.97 |
| Part 1 - Chemovax Schedule B | P10s-MAP-Reactive Immunoglobulin Titers | 9.76 titers | Standard Deviation 13.91 |
| Part 1 - Chemovax Schedule C | P10s-MAP-Reactive Immunoglobulin Titers | 42.25 titers | Standard Deviation 71.94 |
| Part 1 - Chemovax Schedule D | P10s-MAP-Reactive Immunoglobulin Titers | 4.38 titers | Standard Deviation 5.1 |
| Part 1 - Chemovax Schedule E | P10s-MAP-Reactive Immunoglobulin Titers | 6.74 titers | Standard Deviation 7 |