On June 11, 2018 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage biopharmaceutical company focused on creating innovative cancer immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has cleared Investigational New Drug (IND) applications for the Company’s two most advanced product candidates, AB928 and AB122 (Press release, Arcus Biosciences, JUN 11, 2018, View Source [SID1234527262]). Clearance of the first IND for AB928 allows the Company to proceed with its planned Phase 1/1b trial to evaluate the safety, tolerability and preliminary efficacy of AB928 in combination with other agents, including AB122 (the Company’s anti-PD-1 antibody) and chemotherapy, in patients with breast and gynecologic malignancies. Two additional IND applications will be submitted this month which, if cleared, will enable the Company to proceed with trials of AB928 combinations in gastrointestinal malignancies, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). In parallel, the Company has been completing the regulatory process to evaluate the combination of AB928 and AB122 in patients in Australia and expects to dose its first patient with this combination shortly.
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"We are thrilled to receive our first IND clearances to permit dosing in patients for AB928, our dual adenosine receptor antagonist, in combination with other anti-cancer agents," said Terry Rosen, Ph.D., Chief Executive Officer at Arcus. "For our initial Phase 1/1b combination trials for AB928, we have selected tumor types that we believe will be most responsive to adenosine 2 receptor antagonism and combination partners that we expect to be synergistic with this mechanism, specifically immunogenic cell death (ICD) inducing chemotherapy and anti-PD-1 therapy. We have designed our Phase 1/1b program for AB928 to provide us with significant flexibility to open new arms to evaluate promising combinations and to expand or close existing arms based on the emerging data. We are extremely pleased to begin testing in patients the first adenosine 2 receptor antagonist that was specifically designed to be a therapeutic for cancer."
The Phase 1/1b program for AB928 will initially evaluate AB928 in combination with AB122 and with chemotherapy in three tumor-specific trials. The Phase 1/1b program will begin with a dose-escalation phase to identify the optimal dose of AB928 to be combined with fixed doses of AB122 and with each of the three different ICD-inducing chemotherapy regimens. Once the recommended dose of AB928 for each combination has been selected, the tumor-specific trials will enroll expansion cohorts to evaluate AB928 in combination with AB122 or chemotherapy in the following selected tumor types:
Breast and Gynecologic Malignancies. This trial will initially evaluate AB928 in combination with AB122 and with DOXIL in triple negative breast cancer and ovarian cancer. The FDA has cleared the IND application for this trial.
Gastrointestinal Malignancies. This trial will initially evaluate AB928 in combination with AB122 and with mFOLFOX in gastroesophageal and colorectal cancers. The IND application for this trial will be submitted this month.
Lung Cancer and Renal Cell Carcinoma. This trial will initially evaluate AB928 in combination with AB122 in NSCLC and RCC as well as AB928 in combination with a platinum-based chemotherapy regimen in NSCLC. The trial design will also allow for the exploration of additional AB928 combinations, including triple combinations, and AB928 in combination with other anti-PD-1 antibodies. The IND application for this trial will be submitted this month.
Each trial was designed to allow for the addition of new AB928 combination arms in the future. In the dose-escalation portion of the trials, the Company will assess evidence of immune engagement to enable a mechanistic understanding of early clinical responses and will evaluate the suitability of several potential biomarkers for patient enrichment in the dose-expansion cohorts and in future trials.
Data from the dose-escalation portion of the Phase 1/1b program are expected to be available in the first half of 2019.
About AB928
AB928 is an orally bioavailable, highly potent antagonist of the adenosine 2a and 2b receptors. The activation of these receptors by adenosine interferes with the activity of key populations of immune cells and inhibits an optimal anti-tumor immune response. By blocking these receptors, AB928 has the potential to reverse adenosine-induced immune suppression within the tumor microenvironment. AB928 was designed specifically for the oncology setting, with a profile that includes potent activity in the presence of high concentrations of adenosine and a minimal shift in potency due to non-specific protein binding, both essential properties to be efficacious in the tumor microenvironment. AB928 has other attractive features, including high penetration of tumor tissue and low penetration through the healthy blood-brain barrier. In a Phase 1 trial in healthy volunteers, AB928 has been shown to be safe and well tolerated and to have pharmacokinetic and pharmacodynamic profiles consistent with a once-daily dosing regimen.