Trial of Odetiglucan Plus Pembrolizumab for Metastatic Breast Cancer Starts Dosing

Alison Stopeck, MD

The first patients with metastatic hormone-refractory breast cancer in a phase 2 study have been dosed with the combination of odetiglucan (Imprime PGG) and pembrolizumab (Keytruda), announced HiberCell, in a press release.¹

“New treatments to overcome tumor resistance to immunotherapies remain a serious unmet medical need. The fact that the first patients have been dosed with odetiglucan is a positive step forward in our clinical development program. We anticipate that this trial will provide important clinical data to support our understanding of the potential benefits of odetiglucan in combination with pembrolizumab,” said Alison Stopeck, MD, chief of the division of hematology/oncology, associate director of clinical and translational research at the Stony Brook University Cancer Center and chair of the trial steering committee, in a press release.

The multicenter, open-label study (NCT05159778) has a target enrollment of 47 adult patients who have progressed on prior hormone therapy with at least 1 CDK4/6 inhibitor and up to 2 lines of chemotherapy. Following a Simon’s 2-stage design, stage 1 of the study will include 23 patients and stage 2 will include 24 patients. Those enrolled will receive odetiglucan 4 mg/kg via intravenous infusion (IV) over a 2-hour infusion time on days 1, 8, and 15 of each 3-week treatment cycle with pembrolizumab at a fixed dose of 200 mg IV over 30 minutes on day 1 of each 3-week treatment cycle after the infusion of odetiglucan.²

Overall response rate by RECIST v1.1 following treatment with the investigational combination is the primary end point of the study. The secondary survival-related end points include the median progression-free survival (mPFS), PFS rate at months 6, 9, 12, 18, and 24, median overall survival (mOS), and OS rate at months 6, 9, 12, 18, and 24. The study will also evaluate disease control rate and duration of response as secondary efficacy end points.

Safety is another secondary end point of the study along with the correlate changes in immune cell activation marker in tumor samples and in peripheral blood immune cells with treatment outcomes, correlate PD-L1 status and changes in the tumor immune microenvironment with treatment outcomes, correlate levels of serum anti-β-glucan antibody with treatment outcome, and correlate treatment outcome in select metastatic breast cancer subpopulations.

Patients are eligible to enroll given they are at least 18 years of age or older with histologically confirmed metastatic breast cancer that is estrogen receptor- and progesterone receptor-positive. Patients are also required to have peripheral blood levels of IgG anti-β-glucan antibody of greater than, or equal to 20 mcg/mL, documented radiographic or clinical disease progression after treatment CDK4/6 inhibition, measurable disease as per RECIST v1.1, and ECOG performance status of 0 or 1, and a life expectancy of at least 3 months.

Other eligibility requirements for the study include having resolved any prior treatment-related toxicities to a grade 1 or lower, having a negative PCR test at screening for SARS-COV-2 RNA, and having adequate organ function.

Eligible patients are currently being recruited at sites in Minnesota, Missouri, New Mexico, and New York.

“The first patients dosed clinical milestone is a significant step forward in the development of odetiglucan that builds on these prior clinical trials. Importantly, this study continues our patient-centric, patient-first approach that leverages our differentiated therapeutic pipeline to address metastatic disease,” commented Alan Rigby, PhD, president and chief executive officer at HiberCell, in the press release.¹

_REFERENCES:

_{1. HiberCell announces first patients dosed in phase 2 clinical trial of odetiglucan in combination with Keytruda® (pembrolizumab) in adult patients with metastatic, hormone-refractory breast cancer. New release. HiberCell. April 28, 2022. Accessed April 29, 2022. https://bit.ly/3F3zqPB}

_{2. Phase 2 study of Imprime PGG and pembrolizumab in patients with hr+/her2- metastatic breast cancer (mBCA). Clinicaltrials.gov. Updated April 21, 2022. Accessed April 29, 2022.}