The latest advances in breast cancer therapy

Breast cancer research

A number of companies presented breakthrough data for their investigational breast cancer drugs at the San Antonio Breast Cancer Symposium.

Antibody drug conjugate MBRC-101

MBrace Therapeutics presented preclinical data demonstrating the potential of its novel antibody drug conjugate MBRC-101 for the treatment of solid tumours including hormone receptor-positive (HR+) and triple negative breast cancers.

MBRC-101 targets the EphA5 receptor tyrosine kinase, which is present in multiple cancers, including breast, non-small cell lung (NSCLC), colorectal, gastric and pancreatic cancers.

“The data presented today further characterise the safety and activity of MBRC-101 and support its potential to effectively treat various solid tumours, including difficult-to-treat breast cancers,” said Isan Chen, Co-founder, President and Chief Executive Officer at MBrace. “We are advancing our clinical evaluation of MBRC-101 in breast cancer, as well as for patients with other EphA5-expressing solid tumour cancers for whom there is a significant need for targeted treatment options.”

In the data presented, robust and selective EphA5 expression was detected in greater than 80% of triple negative breast cancer (TNBC) and greater than 80% of HR+ breast cancer tissue samples.

The company demonstrated dramatic preclinical efficacy in vivo, with weekly administration of intravenous MBRC-101 showing dose-dependent, robust, and reproducible anti-tumour activity in patient-derived xenograft murine models of TNBC.

PROTAC ER degrader vepdegestrant

Arvinas and Pfizer presented interim data from a Phase Ib trial of vepdegestrant, a novel oral PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in combination with palbociclib (Ibrance).

The data revealed an overall response rate of 42% and median progression-free survival of 11.1 months in heavily pre-treated patients.

The companies plan to broaden development of vepdegestrant to include new combinations with CDK inhibitors in both the first- and second-line settings.

“We are thrilled to see this level of clinical activity in such a heavily pre-treated patient population,” said John Houston, Chairperson, Chief Executive Officer and President at Arvinas. “Vepdegestrant is the only PROTAC ER degrader in late-stage clinical development. The results from this trial evaluating vepdegestrant in combination with palbociclib help advance our goals of benefitting patients with ER+/HER2- breast cancer. It is encouraging to see preliminary signals of activity in both wild-type and ESR1 mutant tumours, with manageable tolerability and low rates of discontinuation.”

Vepdegestrant is currently being evaluated as a monotherapy in the second-line setting in the ongoing Phase III VERITAC-2 trial and in the first-line setting in combination with palbociclib in the ongoing study lead-in cohort of the Phase III VERITAC-3 trial.

The companies shared five additional abstracts at SABCS, including a vepdegestrant monotherapy VERITAC Phase II dose expansion update, a pharmacokinetic/pharmacodynamic (PK/PD) model evaluating the optimal dosing of palbociclib in combination with vepdegestrant, and three additional Trial in Progress abstracts.

CDK4/6 inhibitor ribociclib

Novartis presented the latest analysis of data from the NATALEE trial of Kisqali (ribociclib), which reinforces 25% reduction in risk of recurrence across broad population of patients with early breast cancer.

With 5.6 months of additional follow-up and 78.3% of patients having completed Kisqali treatment, the updated analysis shows sustained invasive disease-free survival (iDFS) benefit and stability in secondary endpoints including overall survival (OS).

The results show a 25.1% in risk of disease recurrence in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer treated with adjuvant Kisqali plus a non-steroidal aromatase inhibitor as standard endocrine therapy.

Kisqali is currently approved in the metastatic setting, where it has consistently demonstrated statistically significant OS benefit across three Phase III trials.

“The final iDFS analysis of NATALEE represents a significant milestone, building upon the robust evidence supporting Kisqali as a potential new adjuvant treatment for a broad, clinically common and identifiable population of patients with stage II and III HR+/HER2- early breast cancer,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development at Novartis. “We are seeking approval for Kisqali in early breast cancer from health authorities worldwide, aspiring to more than double the number of at-risk patients who could potentially benefit from CDK4/6 inhibitor treatment in this setting.”

Diana Spencer, Senior Digital Content Editor, DDW

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