Short summary

The primary objective of the study is to evaluate the safety and tolerability of ALECSAT ("Autologous Lymphoid Effector Cells Specific Against Tumor") in combination with carboplatin and gemcitabine in patients with locally advanced inoperable or metastatic TNBC.

Rationale

The treatment of mTNBC remains the largest unmet need within advanced breast cancer. Chemotherapy has been the primary systemic treatment, with the use of taxanes or anthracyclines as first-line therapy, but duration of responses are short-lasting. No standard of care currently exists for the treatment for metastatic TNBC in any setting.

The adaptive immune system is activated as part of the fight of cancer. However, the cancer cells are able to evade the adaptive immune system, and this is believed to be a key mechanism by which cancer cells survive and relapse. Two main types of cancer immunotherapies have experienced significant progress within the past decade: Immune checkpoint inhibitors and adoptive cell therapy (ACT). A limitation to the use of the ACTs is the toxicity experienced by the patients.

ALECSAT is the acronym for "Autologous Lymphoid Effector Cells Specific Against Tumor". It is a personalized ACT directed towards cancer testis antigens expressed on most solid cancers, incl. TNBC. ALECSAT is an autologous product that induces an immune response against a broad repertoire of CTAs expressed on cancer cells (including TNBC) leading to killing of these cells. Whereas CTAs are silent in normal cells (except germ cells of the testis), they are aberrantly re-expressed in most human solid cancers due to promoter demethylation. Their stable and specific expression on cancer cells and lack of expression on normal tissues make them an attractive target for cancer. Moreover, CTAs are immunogenic, which make them promising candidate targets for cancer immunotherapy.

When combining adaptive cancer immune therapy with chemotherapy, a regimen requiring minimal prednisolone (antiemetic or to avoid infusion-related reactions) as carboplatin/gemcitabine is preferred to maximize the potential for a robust immune response. The chemotherapy regimen gemcitabine/carboplatin is included in ESMO guidelines. ALECSAT has the potential to address the unmet medical need in TNBC. The study population will consist of female patients with locally advanced inoperable breast cancer who cannot be treated with curative intent or with metastatic breast cancer. The potential benefits from treatment with ALECSAT in the study will outweigh the potential risks.

Description of the cohort

Patients treated at the Dept. of Oncology, Odense University Hospital with histologically or cytologically TNBC (defined by absence of HER2 and estrogen receptor (ER) expression on primary tumor) confirmed by local pathologist. Patients initially diagnosed with hormone receptor-positive and/or HER2-positive breast cancer must have confirmation of TNBC in a tumor biopsy obtained from a local recurrence or distant metastasis site.

Patients must be eligible for treatment with carboplatin and gemcitabine.

Data and biological material

Medical records (diagnosis, scans, blood samples, survival, adverse events etc.)