Trials / Unknown

UnknownNCT04197687

TPIV100 and Sargramostim for the Treatment of HER2 Positive, Stage II-III Breast Cancer in Patients With Residual Disease After Chemotherapy and Surgery

Phase II Trial to Evaluate Immune-Related Biomarkers for Pathological Response in Stage II-III HER2-Positive Breast Cancer Receiving Neoadjuvant Chemotherapy With Subsequent Randomization to Multi-Epitope HER2 Vaccine vs. Placebo in Patients With Residual Disease Post-Neoadjuvant Chemotherapy

Status: Unknown
Phase: Phase 2
Study type: Interventional
Enrollment: 480 (estimated)

Sponsor: Academic and Community Cancer Research United · Academic / Other
Sex: Female
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial studies how well TPIV100 and sargramostim work in treating patients with HER2 positive, stage II-III breast cancer that has residual disease after chemotherapy prior to surgery. It also studies why some HER2 positive breast cancer patients respond better to chemotherapy in combination with trastuzumab and pertuzumab. TPIV100 is a type of vaccine made from HER2 peptide that may help the body build an effective immune response to kill tumor cells that express HER2. Sargramostim increases the number of white blood cells in the body following chemotherapy for certain types of cancer and is used to alert the immune system. It is not yet known if TPIV100 and sargramostim will work better in treating patients with HER2 positive, stage II-III breast cancer.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate invasive disease free survival (iDFS) of multi-epitope HER2 vaccine versus (vs.) placebo in combination with ado-trastuzumab emtansine (TTT-DM1) in patients with stage II-III HER2 positive (+) breast cancer (BC) with residual disease post-neoadjuvant chemotherapy. II. To evaluate the safety of multi-epitope HER2 vaccine given concurrently with ado-trastuzumab emtansine (T-DM1) maintenance therapy. SECONDARY OBJECTIVES: I. To evaluate immunogenicity of multi-epitope HER2 vaccine in combination with T-DM1 maintenance therapy. II. To evaluate the immune-related tissue and blood biomarkers for complete pathological response in patients with stage II-III HER2+ BC receiving neoadjuvant chemotherapy. CORRELATIVE RESEARCH OBJECTIVES: I. To determine host immune factors which are critical to prevent disease recurrence in HER2+ BC patients. Ia. To determine if the development of T cell immunity, as assessed by IFN-gamma enzyme-linked immunospot (ELISpot), to HER2 correlates with improved iDFS. Ib. To determine the distribution of the helper T cell response among helper T cell differentiation states. Ic. To determine if augmenting CD4 helper T cell immunity augments HER2-specific antibody immunity induced by trastuzumab. Id. To determine if human leukocyte antigen (HLA) genotypes are associated with antibody responses before and after neoadjuvant therapy and vaccination. Ie. To determine gene expression levels in tumors from patients who did not achieve complete pathological response (pCR) that are associated with recurrence. II. To determine tumor intrinsic genotyping and phenotyping features associated with therapeutic failure to HER2 immune-based approaches. IIa. To determine whether HER2 monoclonal antibody therapy induces HER2 loss and modulation of HER2-specific adaptive immune responses. IIb. To determine loss-of-function mutations in breast tumor that associate with lack of pCR and lack of immune response to HER2+ neoadjuvant treatment. OUTLINE: pCR AFTER NEOADJUVANT CHEMOTHERAPY AND SURGERY: Patients receive standard of care maintenance therapy with trastuzumab and pertuzumab for 1 year in the absence of disease progression or unacceptable toxicity. NO pCR AFTER NEOADJUVANT CHEMOTHERAPY AND SURGERY: Patients are randomized to 1 of 2 arms. ARM I: Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive TPIV100 intradermally (ID) and sargramostim ID on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive two additional booster injections of TPIV100 ID and sargramostim ID at 3 and 12 months after completion of trastuzumab emtansine maintenance therapy. ARM 2: Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive placebo intradermally (ID) and sargramostim ID on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive two additional booster injections of placebo ID and sargramostim ID at 3 and 12 months after completion of trastuzumab emtansine maintenance therapy.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Multi-epitope HER2 Peptide Vaccine TPIV100	Given ID
BIOLOGICAL	Pertuzumab	permitted at physician's discretion
OTHER	Placebo Administration	Given ID
BIOLOGICAL	Sargramostim	Given ID
BIOLOGICAL	Trastuzumab	therapy are at the discretion of the treating physicians
BIOLOGICAL	Trastuzumab Emtansine	at the discretion of the treating physicians.

Timeline

Start date: 2020-02-20
Primary completion: 2025-01-15
Completion: 2025-01-15
First posted: 2019-12-13
Last updated: 2023-12-18

Locations

30 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04197687. Inclusion in this directory is not an endorsement.