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Triple Negative Breast Neoplasms

Breast Diseases

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Pembrolizumab

Vaccines

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

AE37 peptide vaccine every 21 days for 5 doses + Pembrolizumab every 21 days for 2 years (Maximum 35 cycles)

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).

AE37 Peptide vaccine

Pembrolizumab 200 mg IV on day 1 of every 3 week cycle (21 day cycle) for 2 years (35 cycles)

Norman Wolmark, MD

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.

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.

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

A Phase II Clinical Trial of Pembrolizumab in Combination With the AE37 Peptide Vaccine in Patients With Metastatic Triple-Negative Breast Cancer

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 determined by RECIST 1.1 with modifications for progressive disease confirmation

Progression-free survival with pembrolizumab in combination with AE37

Overall survival rate at 1 year from start of therapy.

Clinical benefit rate as measured by disease status by continuous tumor measurement

Adverse events experienced by participants receiving AE37 in combination with pembrolizumab as a measure of toxicity

Spots Global Cancer Trial Database for ae37 peptide vaccine