Ixabepilone Generates Clinical Benefit in Patients With Metastatic Breast Cancer Selected by Companion Diagnostic

Ixabepilone (Ixempra) produced clinical benefit in patients with metastatic breast cancer selected for treatment with the DRP®-IXEMPRA® companion diagnostic (CDx) candidate, according to initial data from a phase 2 trial (NCT04796324) being conducted in Europe.¹

Among 36 patients screened with DRP-IXEMPRA CDx, 5 patients were deemed DRP positive, defined as having a score above 67%. Of the 4 patients evaluable for response at the time of data cutoff, 2 experienced a partial response with tumor shrinkage of 66% and 59%, respectively. Two other patients achieved stable disease for 24 weeks and 19 weeks, respectively.

“We are enthusiastic about these promising very early trial results since the observed clinical benefit rate exceeds what has been historically observed for treatment without the DRP-IXEMPRA CDx patient selection,” Marie Foegh, MD, chief medical officer of Allarity Therapeutics, stated in a news release. “While still early, these data suggest that the use of the DRP-IXEMPRA CDx for patient selection and treatment may help identify patients [with metastatic breast cancer] most able to benefit from this course of treatment, Accordingly, the DRP-IXEMPRA CDx , if approved, may provide clinicians with an important diagnostic to guide patient treatment in this hard-to-treat population.”

Ixabepilone was initially approved by the FDA in 2007, and it is indicated for use in combination with capecitabine for patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated; it is also indicated for use as a single agent in patients with metastatic or locally advanced breast cancer after an anthracycline, a taxane, and capecitabine have failed.²

DRP-IXEMPRA CDx is a clinical-stage companion diagnostic candidate that not yet been approved by the FDA or the European Medicines Agency. The diagnostic features a transcriptomic signature with 191 mRNA biomarkers meant to collectively predict sensitivity or resistance to ixabepilone.¹

The ongoing phase trial being conducted in Europe is enrolling patients at least 18 years of age with histologically or cytologically confirmed locally recurrent or metastatic hormone receptor–positive, HER2-negative or triple-negative breast carcinoma.³

Patients are required to have received no more than 3 prior chemotherapy regimens in the metastatic setting, and prior chemotherapy in any setting must have included a taxane and an anthracycline, unless an anthracycline was not indicated. Any prior number of lines of endocrine therapy are permitted. Patients need to have a DRP score of more than 67%, or more than 33% in the United Kingdom, Belgium, Finland, and the Netherlands. Measurable disease and an ECOG performance status of 0 or 1 are also required.

Key exclusion criteria include HER2-positive tumors; concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drugs during the study period; intracranial disease; clinically significant cardiovascular disease; a stroke within 6 months of day 1 of study treatment; or any other malignancy except for curative intent–treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years of study enrollment.

Patients enrolled to the study are receiving 40 mg/m2 of ixabepilone via a 3-hour intravenous infusion on day 1 of each 3-week cycle.

The primary end point is clinical benefit rate, and secondary end points consist of progression-free survival, overall survival, overall response rate, and safety.

“We are encouraged by these promising, early clinical data suggesting that patients [with metastatic breast cancer] selected for treatment with [ixabepilone ]using our DRP CDx candidate for the drug may have substantially improved clinical benefit versus unselected patients,” James G. Cullem, chief executive officer of Allarity, stated in a press release.¹ “Allarity looks forward to fully enrolling and completing our ongoing phase 2 trial for [ixabepilone] and remains enthusiastic about advancing this program towards market approval in Europe and, if approved, providing European patients [with metastatic breast cancer] with first-time access to this beneficial drug.”

References

1. Initial data from Allarity’s phase 2 trial of Ixempra indicate potential for improved clinical benefit in DRP-selected metastatic breast cancer patients. News release. Allarity Therapeutics. July 5, 2023. Accessed July 6, 2023. https://investors.allarity.com/news/news-details/2023/
2. Ixempra. Prescribing information. R-Pharm US; 2023. Accessed July 6, 2023. https://www.ixempra.com/wp-content/uploads/full_pi.pdf
3. Anti-tumor effect of ixabepilone in metastatic breast cancer (mBC) selected by the ixabepilone DRP. ClinicalTrials.gov. Updated May 31, 2023. Accessed July 6, 2023. https://clinicaltrials.gov/study/NCT04796324