Establishing the Recommended Biological Dose for AE37 Peptide Vaccine in Combination With Pembrolizumab That Will Enhance the Tumor-specific Immune Response and Demonstrate Efficacy in Patients With Advanced Triple-negative Breast Cancer (NSABP FB-14)
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|ClinicalTrials.gov Identifier: NCT04024800|
Recruitment Status : Recruiting
First Posted : July 18, 2019
Last Update Posted : July 18, 2019
This study will look to establish the recommended biologic dose of AE37 in combination with pembrolizumab that will enhance the tumor-specific immune response and demonstrate efficacy in patients with advanced triple-negative breast cancer.
This study will take place in two parts. Stage 1 will be the safety cohort (13 patients) to determine the recommended dose of AE37 vaccine that can safely be administered with pembrolizumab. Stage 2 will be an expansion cohort (16 patients) that will consist of the recommended dose of AE37 determined in Stage 1.
|Condition or disease||Intervention/treatment||Phase|
|Triple-negative Breast Cancer||Biological: AE37 Peptide vaccine Biological: Pembrolizumab||Phase 2|
The FB-14 is an open label, phase II study using pembrolizumab in combination with AE37 peptide vaccine (AE37) in patients with metastatic triple-negative breast cancer (mTNBC).
This study will have a Simon two-stage design. In Stage I (safety cohort), 13 patients will receive combination therapy of AE37 vaccine (without granulocyte macrophage-colony stimulating factor [GM-CSF] adjuvant) 1000 micrograms in two split intradermal injections on Day 1 of cycles 1 through 5 and pembrolizumab 200 mg intravenous infusion (IV) given Day 1 of each cycle for 2 years (1 cycle equals 21 days).
All patients (safety and expansion cohorts) will receive two delayed type hypersensitivity inoculations (DTH): the first within one week prior to beginning study therapy, which must meet the parameters of negative inoculation site assessment for eligibility as described in the protocol; and the second approximately 42 days after the last AE37 vaccine dose.
During a safety run-in, the first 3 patients will be closely followed for 6 weeks following the first dose of study therapy (2 cycles) without further accrual of patients. If one or less of the first 3 patients experience greater than or equal to Grade 3 systemic dose limiting toxicity (DLT) attributable to study therapy during the observation period, the safety run-in portion of the study will proceed with enrollment at the proposed study therapy dose (AE37 1000 micrograms and pembrolizumab 200 mg IV infusion). If there are two or more patients in the safety run-in with DLT during Cycle 1, the dose of AE37 will be decreased to dose level −1 (500 micrograms) to complete stage I accrual. The definition of a DLT is found in the protocol.
If DLT is observed during the safety run-in or in greater than 25% (4 or more) of patients in stage I, the AE37 dose will be de-escalated to 500 micrograms (dose level −1) for all patients to complete stage I accrual. If systemic toxicity occurs in greater than or equal to 3 patients at dose level −1, accrual will be halted and the toxicity reviewed by the study team.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Clinical Trial of Pembrolizumab in Combination With the AE37 Peptide Vaccine in Patients With Metastatic Triple-Negative Breast Cancer|
|Actual Study Start Date :||May 3, 2019|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||June 30, 2024|
Experimental: Arm 1
AE37 peptide vaccine every 21 days for 5 doses + Pembrolizumab every 21 days for 2 years (Maximum 35 cycles)
Biological: AE37 Peptide vaccine
Starting dose: AE37 vaccine 1000 micrograms split into 2 doses given as intradermal injection on day 1 of every 3 week cycle (21 day cycle) for 5 cycles.
Should ≥ grade 3 systemic toxicities (DLT) occur in > 25% (4) of the first 13 patients (4 or more) the study therapy vaccine dose will be de-escalated to 500 micrograms (dose level −1).
Other Name: AE37
Pembrolizumab 200 mg IV on day 1 of every 3 week cycle (21 day cycle) for 2 years (35 cycles)
Other Name: MK-3475
- Recommended dose [ Time Frame: Day 1, within 72 hours of vaccination (48-72 hours), and as adverse events occur in each cycle (21 days) of study therapy (first 13 patients). ]Recommended dose of AE37 that can be safely administered with pembrolizumab. If dose limiting toxicities occur in 4 of the first 13 patients the study therapy vaccine dose will be de-escalated to 500 micrograms (dose-level 1). If fewer than 4 patients experience DLTs then the expansion cohort of 16 patients will be added.
- Objective response rate [ Time Frame: From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) )or two years. ]Objective response rate determined by RECIST 1.1 with modifications for progressive disease confirmation
- Progression-free Survival [ Time Frame: From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years. ]Progression-free survival with pembrolizumab in combination with AE37
- Overall Survival [ Time Frame: From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years. ]Overall survival rate at 1 year from start of therapy.
- Clinical benefit rate [ Time Frame: From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years. ]Clinical benefit rate as measured by disease status by continuous tumor measurement
- Overall Toxicity [ Time Frame: Adverse events assessed from the beginning of study therapy through 90 days after the last dose of study therapy ]Adverse events experienced by participants receiving AE37 in combination with pembrolizumab as a measure of toxicity
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04024800
|Contact: Diana Gosik, RN, BS||412-339-5333||Diana.firstname.lastname@example.org|
|United States, Illinois|
|Cancer Care Specialists of Central Illinois||Recruiting|
|Decatur, Illinois, United States, 62526|
|Crossroads Cancer Center||Recruiting|
|Effingham, Illinois, United States, 62401|
|Cancer Care Specialists of Central Illinois-Swansea||Recruiting|
|Swansea, Illinois, United States, 62226|
|United States, West Virginia|
|West Virginia University||Recruiting|
|Morgantown, West Virginia, United States, 26506|
|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation Inc|