Trial Title:
Personalized Vaccine Immunotherapy in Combination with Checkpoint Inhibitor for Treatment of Triple Negative Breast Cancer
NCT ID:
NCT06324240
Condition:
Anatomic Stage I Breast Cancer AJCC V8
Anatomic Stage IA Breast Cancer AJCC V8
Anatomic Stage IB Breast Cancer AJCC V8
Anatomic Stage II Breast Cancer AJCC V8
Anatomic Stage IIA Breast Cancer AJCC V8
Anatomic Stage IIB Breast Cancer AJCC V8
Anatomic Stage III Breast Cancer AJCC V8
Anatomic Stage IIIA Breast Cancer AJCC V8
Anatomic Stage IIIB Breast Cancer AJCC V8
Anatomic Stage IIIC Breast Cancer AJCC V8
Anatomic Stage IV Breast Cancer AJCC V8
Early Stage Triple-Negative Breast Carcinoma
Locally Advanced Triple-Negative Breast Carcinoma
Metastatic Triple-Negative Breast Carcinoma
Prognostic Stage I Breast Cancer AJCC V8
Prognostic Stage IA Breast Cancer AJCC V8
Prognostic Stage IB Breast Cancer AJCC V8
Prognostic Stage II Breast Cancer AJCC V8
Prognostic Stage IIA Breast Cancer AJCC V8
Prognostic Stage IIB Breast Cancer AJCC V8
Prognostic Stage III Breast Cancer AJCC V8
Prognostic Stage IIIA Breast Cancer AJCC V8
Prognostic Stage IIIB Breast Cancer AJCC V8
Prognostic Stage IIIC Breast Cancer AJCC V8
Prognostic Stage IV Breast Cancer AJCC V8
Recurrent Breast Carcinoma
Unresectable Triple-Negative Breast Carcinoma
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Pembrolizumab
Ipilimumab
Vaccines
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Ipilimumab
Description:
Given IV
Arm group label:
Phase Ib Arm B ( TMV vaccine, ipilimumab)
Other name:
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
Other name:
BMS-734016
Other name:
Ipilimumab Biosimilar CS1002
Other name:
MDX-010
Other name:
MDX-CTLA4
Other name:
Yervoy
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Phase Ib Arm A ( TMV vaccine, pembrolizumab)
Other name:
BCD-201
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
Pembrolizumab Biosimilar BCD-201
Other name:
SCH 900475
Intervention type:
Biological
Intervention name:
Vaccine Therapy
Description:
Given TMV vaccine ID
Arm group label:
Phase Ia (TMV vaccine)
Arm group label:
Phase Ib Arm A ( TMV vaccine, pembrolizumab)
Arm group label:
Phase Ib Arm B ( TMV vaccine, ipilimumab)
Summary:
This phase I trial tests the safety, side effects, and best dose of a personalized
vaccine (tumor membrane vesicle or TMV vaccine) by itself and in combination with
checkpoint inhibitor (pembrolizumab or ipilimumab) in treating patients with triple
negative breast cancer. This vaccine is made by taking a piece of patient's triple
negative breast cancer to design a vaccine to stimulate the immune system's memory.
Patients are treated with the personalized vaccine immunotherapy with or without
monoclonal antibodies, such as pembrolizumab and ipilimumab. This approach may help the
body's immune system attack the cancer, and may interfere with the ability of tumor cells
to grow and spread. Giving personalized TMV vaccine with pembrolizumab or ipilimumab may
help the immune system attack cancer better and reduce the risk of this breast cancer
coming back or growing.
Detailed description:
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of TMV vaccine when delivered intradermally
as monotherapy in patients with early stage TNBC for Phase 1a. II. To determine immune
stimulating activity and an optimal biological dose (OBD) of TMV vaccine when delivered
intradermally as monotherapy for Phase 1a.
III. To determine the safety and tolerability of TMV vaccine under OBD when delivered
intradermally in combination with PD-1-inhibitor pembrolizumab or CTLA-4 inhibitor
ipilimumab in patients with metastatic TNBC (mTNBC) and patients with early stage TNBC
for Phase 1b.
SECONDARY OBJECTIVES:
I. To determine immune stimulating activity of TMV vaccine when delivered intradermally
as in combination with checkpoint inhibitor therapy in adult patients with TNBC (TNBC)
for Phase 1b.
II. To assess the disease control rate (DCR) and overall response rate (ORR) of TMV
vaccine in combination with checkpoint inhibitor therapy when administered to adult
patients with mTNBC.
III.To assess effect of TMV vaccine monotherapy and in combination with checkpoint
inhibitor therapy on progression-free survival (PFS) and overall survival (OS) when
administered to adult patients with TNBC
EXPLORATORY OBJECTIVES:
I.To examine the association of PD-L1 expression with the immune stimulating activity of
TMV vaccine when administered as monotherapy and in combination with checkpoint inhibitor
therapy.
II. To assess association of TIL density with the immune stimulating activity of TMV
vaccine when administered as monotherapy and in combination with checkpoint inhibitor
therapy.
III. To assess association of BRCA 1/2 mutation status with the immune stimulating
activity of TMV vaccine when administered as monotherapy and in combination with
checkpoint inhibitor therapy.
OUTLINE: This is a phase Ia dose-escalation study of TMV vaccine followed by a phase Ib
dose-expansion study.
PHASE IA: Patients receive TMV vaccine intradermally (ID) at weeks 1, 3, and 5 in the
absence of disease progression or unacceptable toxicity.
PHASE IB: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive TMV vaccine ID at weeks 1, 3, and 5 in the absence of disease
progression or unacceptable toxicity. Patients also receive pembrolizumab intravenously
(IV) on day 1. Treatment with pembrolizumab repeats every 21 days for 6-9 cycles in the
absence of disease progression or unacceptable toxicity.
ARM B: Patients receive TMV vaccine ID at weeks 1, 3, and 5 in the absence of disease
progression or unacceptable toxicity. Patients also receive ipilimumab IV on day 1.
Treatment with ipilimumab repeats every 21 days for 4 cycles in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for up to 2
years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Written informed consent and Health Insurance Portability and Accountability Act
(HIPAA) authorization for release of personal health information
- Must be age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14
days prior to tissue consent
- Absolute neutrophil count > 1500/mcL (obtained within 14 days prior to vaccine
administration)
- Absolute lymphocyte count >= 600 cells/µl (obtained within 14 days prior to vaccine
administration)
- Platelets > 100,000 mm (obtained within 14 days prior to vaccine administration)
- Hemoglobin > 9.0 g/dL (obtained within 14 days prior to vaccine administration)
(NOTE: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >
9.0g/dl is acceptable)
- Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine
clearance >= 60 mL/min using Cockcroft-Gault equation for patients with creatinine
levels > 1.5 x institutional ULN (obtained within 14 days prior to vaccine
administration)
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< 1 x ULN (obtained within 14 days
prior to vaccine administration)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
unless liver metastases are present, in which case they must be =< 5 x ULN (obtained
within 14 days prior to vaccine administration)
- Bilirubin =< 1.5 X ULN (except in participants with documented Gilbert's disease,
who must have a total bilirubin =< 3.0 mg/dL) (obtained within 14 days prior to
vaccine administration)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless
patient is receiving anticoagulant therapy as long as PT or partial thromboplastin
time (PTT) is within therapeutic range of intended use of anticoagulants (obtained
within 14 days prior to vaccine administration)
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of
intended use of anticoagulants (obtained within 14 days prior to vaccine
administration)
- TNBC as defined by estrogen receptor (ER)/progesterone receptor (PR) =< 10% if
Allred =< 3; Her2/neu negative as defined by scores of 0 or 1+ by
immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ
hybridization (FISH) ratio of < 2.0 or < 6 Her2 copies per cell
- Patients with metastatic or inoperable locally advanced disease: Metastatic or
inoperable locally advanced disease is defined as either histologically confirmed
metastatic breast cancer by biopsy; or locally advanced breast cancer that, in the
opinion of the treating physician, is not amenable to curative intent surgical
resection; or, radiological or clinical evidence suggestive and supportive of
metastatic disease
- Documented metastatic biopsy is not required provided the patient has a prior
diagnosis of TNBC that otherwise meets the eligibility criteria
- Eligible patients must have =< 3 lines of chemotherapy in the
metastatic/advanced disease setting. For patients who have relapsed within 6
months of systemic therapy given within curative intent, that therapy will
count as a line of metastatic therapy. Last cycle of cytotoxic therapy must be
>= 21 days prior to cycle (C)1 day (D)1 of vaccine. Last cycle of checkpoint
inhibitor therapy be >= 28 days prior to C1D1 of vaccine. Last dose of
radiotherapy must be >= 14 days prior to C1D1 of vaccine
- Prior checkpoint inhibitor is permitted. Patients who are known to have PD-L1
positive with combined positive score (CPS) >= 10 will be required to have had
pembrolizumab therapy prior to enrollment
- Patients who are metastatic or inoperable, locally advanced will only be
eligible for the Phase 1b combination cohort. They will not be eligible for the
Phase 1a dose escalation cohort. Patients who have received prior anti-CTLA-4
antibody will preferentially be enrolled to cohort B (combination of TMV
vaccine with pembrolizumab). Patients who have received prior PD-L1 or PD-1
antibody therapy will preferentially be enrolled to cohort C (combination of
TMV vaccine with ipilimumab). Patients with metastatic disease who have
received no prior immune checkpoint inhibitor therapy will be assigned to a
treatment arm based on available slots and discretion of treating physician
- Patients with early stage TNBC: Early stage TNBC is defined as clinical or
pathologic Stage I-III TNBC
- After resection of disease in the breast and axilla, early stage patients are
eligible for either the Phase 1a dose escalation of TMV vaccine monotherapy
Cohort A or the Phase 1b combination arm of the vaccine with immune checkpoint
inhibitor (ICI)
- Patients will be required to have completed adjuvant radiotherapy (if
indicated) >= 14 days prior to initiation of vaccine on trial
- Patients who have residual disease after completion neoadjuvant therapy that
proceed with adjuvant capecitabine can enroll >= 28 days after completion of
final dose of capecitabine. Patients electing to enroll onto the Phase 1a
Cohort A monotherapy arm can enroll prior to initiation of capecitabine,
however must not initiate capecitabine prior to the Week 12 blood draw
(measurement of immune biomarkers) on study
- Patients who have a germline BRCA 1/2 mutation that meet the Food and Drug
Administration (FDA) indication for use of adjuvant Olaparib can enroll >= 28
days after completion of final dose of olaparib. Patients electing to enroll
onto the Phase 1a Cohort A monotherapy arm can enroll prior to initiation of
olaparib, however must not initiate olaparib prior to the Week 12 blood draw
(measurement of immune biomarkers) on study
- Patients who undergo upfront surgery: Patients may initiate injection of
vaccine >= 28 days after completion of final cycle of adjuvant chemotherapy
- Patients who have early stage breast cancer that have residual disease after
completing neoadjuvant chemotherapy with the KEYNOTE 522 regimen (pembrolizumab
at a dose of 200 mg every 3 weeks plus weekly paclitaxel and carboplatin for 4
cycles followed by pembrolizumab-doxorubicin-cyclophosphamide or of
pembrolizumab-epirubicin-cyclophosphamide every 3 weeks for 4 cycles):
- Patient enrolling onto Phase 1a Cohort A will initiate injection of
vaccine >= 28 days after completion of final cycle of standard of care
adjuvant pembrolizumab
- Patient enrolling onto Phase 1b Cohort B or C will initiate injection of
vaccine >= 28 days surgical resection. Patients who have received
pembrolizumab as part of the preoperative KEYNOTE 522 regimen will
preferentially be enrolled to cohort B (combination of TMV vaccine with
pembrolizumab) and will receive up to 9 cycles of adjuvant pembrolizumab
every 3 weeks as per standard of care. Vaccine will be administered every
2 weeks for 3 doses prior to the first three ICI cycles
- Patients who have early stage breast cancer that have that have residual
disease after completing neoadjuvant chemotherapy with either dose-dense
doxorubicin-cyclophosphamide followed by paclitaxel or
docetaxel-cyclophosphamide:
- Patient enrolling onto Phase 1a Cohort A will initiate injection of
vaccine >= 28 days surgical resection
- Patient enrolling onto Phase 1b Cohort B or C will initiate injection of
vaccine >= 28 days surgical resection. Patients will be assigned to
receive either pembrolizumab (Cohort B) every 3 weeks for 6 cycles or
ipilimumab (Cohort C) every 3 weeks for 4 cycles in combination with TMV
vaccine based on available slots in each arm and discretion of treating
physician. Vaccine will be administered every 2 weeks for 3 doses; the TMV
vaccine will be administered prior to the ICI cycle if ICI is due.
- Weight of tumor tissue for production of vaccine must be at least 1 gram. In
metastatic patients, preferentially, invasive tumor in breast or lymph node tissue
will be retrieved by excisional biopsy to ensure sufficient yield. In metastatic
patients who undergo initiation of first-line standard of care systemic therapy off
study (i.e. pembrolizumab and chemotherapy in a PD-L1 positive patient), then
ideally collection of tumor tissue will occur prior to treatment initiation of
standard of care therapy to maximize cellularity. Metastatic patients who have
undergone mastectomy during curative treatment initially or have no invasive disease
in the breast, chest wall, or accessible regional lymph nodes, will be evaluated for
image-guided core biopsies of liver metastasis or video-assisted thorascopic wedge
resection of lung metastasis
- In patients with early stage TNBC undergoing upfront surgery, the tumor tissue
will be retrieved during lumpectomy/mastectomy. In early stage patients who are
identified as high risk of having residual disease after neoadjuvant
chemotherapy or undergo upfront resection, tissue will be retrieved during
planned lumpectomy or mastectomy
- Measurable disease is not required in metastatic patients but patients must have
sufficient tumor to yield 1g on biopsy to enable production of personalized TMV
vaccine product
- Patients will undergo germline testing to assess for a BRCA1/BRCA2 deleterious
mutation. Knowledge of germline status is not required to enroll on the study
- Able and willing to complete the entire study according to the study schedule
- Patients must give written informed consent. A copy of the signed informed consent
form will be retained in the patient's chart
Exclusion Criteria:
- Weight of the tumor tissue is less 1 gram
- Clinically significant comorbid conditions such as cardiovascular disease or
significant peripheral vascular (e.g., uncontrolled hypertension, myocardial
infarction, unstable angina) within 6 months of study entry, serious cardiac
arrhythmia requiring medication, and uncontrolled infection
- No second malignancy except prior breast cancer or except non-melanomatous skin
cancer within the past 5 years
- Ongoing or planned systemic anti-cancer therapy or radiation therapy. Last cycle of
cytotoxic therapy must be >= 21 days prior to C1D1 of vaccine. Last cycle of
checkpoint inhibitor therapy be >= 28 days prior to C1D1 of vaccine. Last dose of
radiotherapy must be >= 14 days prior to C1D1 of vaccine
- Pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the pre-screening or screening visit
through 120 days after the last dose of study treatment
- Has a known history of active tuberculosis (Bacillus Tuberculosis)
- History of allogeneic organ transplant
- Known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate
provided they are stable (without evidence of progression by imaging for at least 4
weeks prior to the first dose of study treatment and any neurologic symptoms have
returned to baseline), have no evidence of new or enlarging brain metastases, and
are not using steroids for management of brain metastases for at least 7 days prior
to study treatment. This exception does not include carcinomatous meningitis which
is excluded regardless of clinical stability
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of study
treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic
corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid
- Active autoimmune disease that has required systemic treatment in the past 2 years
(i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment
- Known history of non-infectious pneumonitis that required steroids or any evidence
of active pneumonitis
- Failure to recover from grade 3 or 4 toxicity from previous treatment
- For the combination cohort: prior grade 4 immune-related adverse events due to
previous ICI. Patients who experienced grade 2 or 3 toxicity with prior ICI therapy
may enroll if toxicity reverted to =< grade 1
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Grady Health System
Address:
City:
Atlanta
Zip:
30303
Country:
United States
Facility:
Name:
Emory University Hospital Midtown
Address:
City:
Atlanta
Zip:
30308
Country:
United States
Contact:
Last name:
Deborah Omoyege
Email:
deborah.omoyege@emory.edu
Contact backup:
Last name:
Keerthi Gogineni, MD, MSHP
Facility:
Name:
Emory University Hospital/Winship Cancer Institute
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Contact:
Last name:
Deborah Omoyege
Email:
deborah.omoyege@emory.edu
Contact backup:
Last name:
Keerthi Gogineni, MD, MSHP
Facility:
Name:
Emory Saint Joseph's Hospital
Address:
City:
Atlanta
Zip:
30342
Country:
United States
Contact:
Last name:
Deborah Omoyege
Email:
deborah.omoyege@emory.edu
Contact backup:
Last name:
Keerthi Gogineni, MD, MSHP
Start date:
December 31, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Emory University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Emory University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06324240