Phase 1 Clinical Trial of a Personalized Cancer Vaccine (PCV) Strategy +/- AB248 (CD8-selective IL-2 Mutein Fusion Protein) in Patients With a New Diagnosis of Triple Negative Breast Cancer Undergoing Neoadjuvant Chemoimmunotherapy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine (PCV) strategy with or without CD8-selective IL-2 mutein fusion protein in patients with triple negative breast cancer undergoing neoadjuvant chemoimmunotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Step 0 Inclusion Criteria:
- •Newly diagnosed, previously untreated, locally advanced non-metastatic triple negative breast cancer (as defined by the most recent ASCO/CAP guidelines). Permissible staging per AJCC is as follows:
- •T1c, N1-N2
- •T2, N0-N2
- •T3, N0-N2
- •At least 18 years of age.
- •Adequate tissue available for nucleic acid isolation/PCV design or willing to undergo biopsy if adequate tissue is not available.
- •Adequate cardiac function per treating physician and a candidate for the KEYNOTE 522 regimen (or receiving the KEYNOTE 522 regimen for no more than one month). Note that patients who are already receiving the KEYNOTE 522 regimen at the time of screening must have adequate archival tissue for nucleic acid isolation/PCV design (biopsy will not be permitted).
- •TIL percentage < 10% (performed on SOC biopsy).
- •Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
排除标准
- •Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
- •Received prior chemotherapy, targeted therapy, or radiation therapy within the past 12 months.
- •Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor.
- •Currently receiving any other investigational agents.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in the study.
- •Received a live vaccine within 30 days of the first dose of pembrolizumab.
- •Active autoimmune disease that has required systemic treatment in the past 2 years.
- •Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.
- •History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
- •Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
- •Known history of active TB (bacillus tuberculosis).
- •Known history of HIV.
- •Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
- •History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
- •Step 1 Inclusion Criteria:
- •ECOG performance status ≤ 1 within 10 days of initiation of PCV
- •Adequate bone marrow and organ function within 28 days of initiation of PCV as defined below:
- •Absolute neutrophil count ≥ 1.0 K/cumm
- •Platelets ≥ 100 K/cumm
- •Hemoglobin ≥ 8.0 g/dL
- •Total bilirubin ≤ 1.5 x IULN
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- •Creatinine clearance > 30 mL/min by Cockcroft-Gault
- •The effects of the PCV on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after last dose of PCV. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
- •Received at least 4 months of the KEYNOTE 522 regimen.
- •Step 1 Exclusion Criteria:
- •Currently receiving any other investigational agents.
- •Pregnant and/or breastfeeding.
- •Experiencing ongoing AEs related to the SOC KEYNOTE 522 regimen that have not resolved to < grade
- •Patients may be permitted to enroll with a grade 3 AE with approval of the PI and treating physician.
- •QTcF > 470 msec.
研究组 & 干预措施
Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Personalized cancer vaccine (PCV) (Biological)
Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: pVAC tools neoantigen prediction algorithm (Other)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Personalized cancer vaccine (PCV) (Biological)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: pVAC tools neoantigen prediction algorithm (Other)
Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Doxorubicin (Drug)
Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Paclitaxel (Drug)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: AB248 (Drug)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: poly-ICLC (Drug)
Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: poly-ICLC (Drug)
Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Pembrolizumab (Drug)
Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Carboplatin (Drug)
Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Cyclophosphamide (Drug)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Doxorubicin (Drug)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Cyclophosphamide (Drug)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Pembrolizumab (Drug)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Paclitaxel (Drug)
Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCV + Pembrolizumab+AB248
Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen. Approximately 2 weeks after the conclusion of SOC neoadjuvant therapy but prior to SOC surgery, patients will start the personalized cancer vaccine (PCV). Patients will receive 5 doses of the PCV + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCV + poly-ICLC on days 43, 64, and 85 along with SOC adjuvant pembrolizumab.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Treatment-emergent adverse events (TEAEs)
时间窗: Step 1 enrollment to 30 days after completion of PCI treatment (estimated time of 115 days)
Treatment-emergent adverse events (TEAEs) will be assessed via CTCAE v5.
Treatment-related adverse events (TRAEs)
时间窗: Step 1 enrollment to 30 days after completion of PCI treatment (estimated time of 115 days)
Treatment-related adverse events (TRAEs) will be assessed via CTCAE v5.
Serious adverse events (SAEs)
时间窗: Step 1 enrollment to 30 days after completion of PCI treatment (estimated time of 115 days)
Serious adverse events (SAEs) will be assessed via CTCAE v5.
Feasibility as determined by number of enrolled patients with triple negative breast cancer
时间窗: Completion of enrollment (1 day for patient)
Defined as enrolling 24 evaluable patients in 36 months.
Feasibility as determined by time required for PCI design and manufacture
时间窗: Start of Step 0 Enrollment to PCI completion (estimated time of 24 weeks)
Defined as completion of design and manufacture within 24 weeks.
Feasibility as determined by rate of successful PCI delivery
时间窗: Day 1
Defined as at least 70% of patients receiving at least one dose of PCI.
Treatment-emergent adverse events (TEAEs)
时间窗: Step 1 enrollment to 30 days after completion of PCV treatment (estimated time of 115 days)
Treatment-emergent adverse events (TEAEs) will be assessed via CTCAE v6.
Treatment-related adverse events (TRAEs)
时间窗: Step 1 enrollment to 30 days after completion of PCV treatment (estimated time of 115 days)
Treatment-related adverse events (TRAEs) will be assessed via CTCAE v6.
Serious adverse events (SAEs)
时间窗: Step 1 enrollment to 30 days after completion of PCV treatment (estimated time of 115 days)
Serious adverse events (SAEs) will be assessed via CTCAE v6.
Feasibility as determined by time required for PCV design and manufacture
时间窗: Start of Step 0 Enrollment to PCV completion (estimated time of 24 weeks)
Defined as completion of design and manufacture within 24 weeks.
Feasibility as determined by rate of successful PCV delivery
时间窗: Day 1
Defined as at least 70% of patients receiving at least one dose of PCV.
次要结局
- Immune response as evaluated by ELISPOT analysis.(Step 0 Enrollment to 12 months after PCI completion (estimated time of 18 months and 85 days))
- Recurrence-free survival (RFS)(Step 1 enrollment through completion of follow up (estimated time of 5 years and 85 days))
- Immune response as evaluated by ELISPOT analysis.(Step 0 Enrollment to 12 months after PCV completion (estimated time of 18 months and 85 days))