RECAST DCIS

The Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: Ductal Carcinoma In Situ (RECAST DCIS) Platform Trial is a landmark Phase 2 trial that is changing the lens through which we treat DCIS. The study is aimed at preventing the progression of DCIS to breast cancer and is evaluating three investigational endocrine therapy arms.

With the objective to avoid over-treatment of low-risk DCIS patients, this new trial offers DCIS patients endocrine therapy with the intent to identify patients who are responsive to non-invasive treatment and have the option to omit surgery and be monitored via long-term active surveillance. A key element in reducing over treatment of DCIS is identifying biomarkers that reflect the risk of progression so that those with low-risk lesions are spared surgery. RECAST DCIS features the assessment of MRI imaging and molecular-based biomarker analyses in addition to evaluating new investigational agents in this setting. If patients and their physicians agree, they may be able to stay on endocrine therapy for up to three years.

DCIS Treatment, Re-Imagined

The three collaborators for this trial, Atossa Therapeutics, Havah therapeutics, and Stemline, all aim to find alternative solutions for DCIS patients and are providing different agents for assessment.

Atossa’s (Z)-endoxifen

Atossa’s (Z)-endoxifen has the potential to mitigate breast cancer risk ; to reduce cancer cell activity before surgery; and to reduce the risk of recurrent or new breast cancer after the initial treatment. According to published studies, (Z)-endoxifen is a competitive inhibitor of ER and represses ER transcriptional activity. (Z)-endoxifen is 100-fold more potent in anti-estrogen activity compared to other Selective Estrogen Receptor Modulators (SERMs). In addition to its potent anti-estrogen effects, (Z)-endoxifen at higher concentrations has been shown to target PKCβ1, a known oncogenic protein. (Z)-endoxifen also appears to deliver similar or even greater bone agonistic effects while resulting in little or no endometrial proliferative effects compared with tamoxifen. The National Cancer Institute (NCI) and others have studied (Z)-endoxifen and have demonstrated promising results in the treatment of breast cancer as well as for the treatments of other solid tumors. Treatment with (Z)-endoxifen may avoid off target effects of tamoxifen and remaining metabolites, potentially increasing adherence by improving the safety profile.

Havah Therapeutics' HAVAH T+Ai™

Havah therapeutics’ HAVAH T+AiTM combines testosterone, the natural ligand for the androgen receptor and an aromatase inhibitor (Ai) which inhibits the conversion of testosterone to estradiol, to modulate the growth of abnormal breast tissues. HAVAH T+AiTM is a proprietary combination subcutaneously delivered system to overcome hormonal symptoms by balancing hormonal irregularities in the breast, developed from more than 10 years of clinical research into hormonal regulation in women. Havah has extensive clinical experience using HAVAH T+AiTM to address pre- and postmenopausal prevention of breast disease, and the company generated data from more than 1,000 women with breast disease through an ongoing open-label cohort study (More than 8,200 implants), with critical safety pharmacokinetic and early efficacy data already demonstrated.

Stemline’s Elacestrant (ORSERDU)

Stemline’s Elacestrant (ORSERDU) is a selective estrogen receptor degrader, taken orally once daily as a tablet. It is an antagonist that selectively binds to ERa and acts to inhibit estrogen receptor expression via degradation and estradiol-mediated cell proliferation. ORSERDU was approved by the U.S. Food & Drug Administration in January 2023 for the treatment of post-menopausal women or adult men with estrogen receptor (ER)-positive, HER2-negative, ESR-1 mutated advanced or metastatic breast cancer, following at least one line of endocrine therapy. For more information about prescribing guidelines, please visit https://www.orserdu.com/