Polaris Group Announces Results of a Phase 1 Clinical Study with its Lead Therapeutic Candidate ADI-PEG 20 in Combination with Pembrolizumab for Advanced Solid Tumors

SAN DIEGO, June 04 2018 – At the American Society Clinical Oncology’s 2018 annual meeting, scientists from National Institute of Cancer Research Taiwan reported results from a phase 1 clinical study, showing that Polaris lead therapeutic candidate ADI‑PEG 20 in combination with pembrolizumab has activity for advanced solid tumors.

The study results showed that ADI‑PEG 20 could be safely combined with pembrolizumab at its full dose (200 mg) for the treatment of advanced solid tumors.  In the dose escalation cohort, two patients, one with thymus cancer and one with nasopharyngeal carcinoma, both in the fourth-line systemic treatment, had a partial response (PR). The main toxicity has been transient and manageable neutropenia. The study is currently enrolling patients in two recommended phase 2 dose cohorts: one for advanced cancers with low PD-L1 expression and one for head and neck cancer. Overall, the study has an objective response rate (ORR) of 27.8% (5/18) in evaluable patients at this time.

In the advanced cancers with low PD-L1 expression cohort, only patients with less than 50% PD-L1 expression are eligible for entry. Of the first 8 evaluable patients in this group, the current ORR is 37.5% as 3 PRs have been observed in heavily pre-treated patients: a third-line mucosal melanoma, a fifth-line cholangiocarcinoma and a fourth-line esophageal carcinoma. These preliminary results suggest that ADI-PEG 20 could potentially be synergistic with program death compounds, and various combinations that include ADI‑PEG 20 and other immunotherapies should be further explored in multiple cancer types.

“Preclinical data indicated that ADI‑PEG 20 could up-regulate PD-L1 expression, turning immune ‘cold’ tumors to express PD-L1 and thus more receptive to programmed death inhibition with agents such as pembrolizumab. We are gratified to see this same scenario occur in patients,” said John Bomalaski, M.D., Executive Vice President, Medical Affairs, of Polaris. “Based on this encouraging data, we now have multiple trials planned with ADI‑PEG 20 and various checkpoint inhibitors, including combinations with both programmed death and CTLA-4 inhibitors. The enhancement of sensitivity to programmed death inhibition, combined with ADI-PEG 20’s efficacy, tolerability, and different mechanism of action make it an ideal agent for incorporation into checkpoint agent therapy,” he added.

About ADI-PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed.  Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.

About Polaris Group

Polaris Group specializes in the research and development of protein drugs to treat cancer and other debilitating diseases. In addition to the ADI‑PEG 20 program, Polaris Group is developing other therapeutic agents, including a small molecule drug program that utilizes a rational structure-based approach to design novel compounds that inhibit the biological function of cancer-related protein targets.