Ixabepilone CDx May Effectively Identify DRP+ Metastatic Breast Cancer

Among 36 screened patients, DRP-IXEMPRA CDx identified 5 patients who were positive for DRP. Investigators identified signs of clinical benefit in 4 of these patients, including 1 with a partial response (PR) and 66% tumor shrinkage, 1 with a PR and 59% tumor shrinkage, 1 with 24 weeks of stable disease, and 1 with 19 weeks of stable disease.

Drug Response Predictor (DRP®)-IXEMPRA® companion diagnostic (CDx) demonstrated promise in identifying patients eligible for treatment with ixabepilone (Ixempra), which appeared clinically beneficial in several patients, according to a press release on findings from a European phase 2 clinical trial.¹

Among 36 screened patients, DRP-IXEMPRA CDx identified 5 patients who were positive for DRP. Investigators identified signs of clinical benefit in 4 of these patients, including 1 with a partial response (PR) and 66% tumor shrinkage, 1 with a PR and 59% tumor shrinkage, 1 with 24 weeks of stable disease, and 1 with 19 weeks of stable disease.

According to the press release, the current FDA-approved label for ixabepilone highlights an objective response rate (ORR) of 12.4% and a clinical benefit rate (CBR) of 24.8% when administered on its own to patients with metastatic or locally advanced breast cancer. Based on interim data from the study, developers believe that patient selection with the DRP-IXEMPRA CDx may elicit a higher ORR and CBR compared with the rates listed on the FDA-approved label for ixabepilone monotherapy.

Investigators expect to have a readout of further data before the end of 2023.

“We are enthusiastic about these promising very early trial results since the observed clinical benefit rate exceeds what has been historically observed for [ixabepilone] treatment without the DRP-IXEMPRA CDx patient selection,” Marie Foegh, MD, chief medical officer at Allarity Therapeutics, said in the press 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.”

The DRP-IXEMPRA CDx is designed to select patients who may have a high probability of responding to treatment with ixabepilone based on the genetic signature of their cancer. Specifically, the assay includes 191 mRNA biomarkers, which collectively predict tumor sensitivity or resistance to ixabepilone. Developers hypothesize that selecting and treating patients with a sufficiently high DRP score may significantly boost therapeutic responses.

Investigators of the ongoing, open-label, single-arm, European phase 2 study are evaluating the efficacy of ixabepilone among patients with locally recurrent or metastatic breast cancer previously treated with 3 or fewer lines of chemotherapy, which must include a taxane and an anthracycline. Patients underwent screening with the DRP-IXEMPRA CDx and subsequently received a DRP score. Those with a DRP score higher than 67% proceeded to treatment with ixabepilone.

The primary goal of the study is refining the DRP-IXEMPRA CDx criteria and expanding the enrollment of the patients with metastatic breast cancer who may benefit from ixabepilone.

Investigators previously announced that the first patient enrolled on the European phase 2 trial in March 2021.²

“I am pleased to see the first patient enrolled in our European phase 2 trial for [ixabepilone],” Foegh said in a press release at the time of the trial’s initiation. “We look forward to further evaluating the clinical and therapeutic value of [DRP-IXEMPRA CDx], and to providing individuals with metastatic breast cancer another therapeutic option through our personalized medicine approach.”

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, Inc. July 5, 2023. Accessed July 6, 2023. https://shorturl.at/oCU47
2. Allarity Therapeutics initiates phase 2 trial of IXEMPRA® in Europe for the treatment of metastatic breast cancer. News release. Allarity Therapeutics. March 4, 2021. Accessed July 6, 2023. https://bit.ly/3XE3t9M