Personalized Vaccine Immunotherapy in Combination With Checkpoint Inhibitor for Treatment of Triple Negative Breast Cancer

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.