AB122 Controls Disease in Half of Solid Tumor Patients in Phase 1 Trial

AB122 Controls Disease in Half of Solid Tumor Patients in Phase 1 Trial

A potential antibody treatment called AB122 enabled tumor reduction and stable disease in half of patients with ovarian cancer and other types of advanced tumors, according to early results of an Arcus Biosciences Phase 1 trial.

The findings from a small number of patients also revealed that AB122 benefits were similar to that of the approved therapies Opdivo (nivolumab) and Keytruda (pembrolizumab).

AB122 is a monoclonal antibody that selectively targets a protein receptor called PD-1 in immune T-cells, blocking its binding to PD-L1 and PD-L2 in cancer cells. This binding is used by tumor cells to evade immune attack.

According to Arcus, preclinical work has shown that the biological and pharmacological properties of AB122 are similar to those of Bristol-Myers Squibb’s Opdivo and Merck’s Keytruda, which are immune checkpoint inhibitors also targeting PD-1 antibodies.

In a press release, Joyson Karakunnel, MD, Arcus’ vice president of clinical development, said the data “represent an important step in confirming these results in patients.”

The Phase 1 dose-escalation trial intends to assess the safety, immunogenicity — the ability to trigger an immune response — and clinical activity of AB122. Three dosing regimens — 80 mg, 240 mg, and 360 mg — are being evaluated to identify doses of AB122 that can be administered every two, three, or four weeks.

At the time of the analysis — Oct. 5, 2018 — 20 patients had been treated, including seven with ovarian cancer, three with colorectal cancer, three with endometrial cancer, two with gastroesophageal cancer, and one each with either bladder, head and neck, breast, non-small cell lung, or prostate cancer.

In patients treated every two weeks, 80 mg dosing was evaluated in three patients, 240 mg in six, and 360 mg in one. Also, 360 mg and 480 mg (five patients each) are being evaluated for the every-three-week and every-four-week dosing regimens, respectively.

In agreement with the approved anti-PD-1 antibodies, the 240-mg dose enabled full and sustained PD-1 receptor occupancy on peripheral blood T-cells across all time points in most patients. The results “support the selection of 240 mg as the AB122 dose for administration every two weeks,” Karakunnel said.

Two patients on the every-two-week regimen showed reduced tumor size, one with ovarian cancer on 360 mg and the other with head and neck cancer on 80 mg. Also, treatment enabled stable disease in one patient with ovarian cancer, two with colorectal cancer, and one with head and neck cancer, accounting for a disease control rate of 50%.

Treated patients stayed on study from 0.8 to 9.9 months. AB122 was well-tolerated at all doses, with most treatment-emergent adverse events being mild to moderate. The most common were fatigue, diarrhea, and nausea. Three patients had serious adverse events — respiratory tract infection, fever, and elevated liver function tests secondary to the formation of gallstones — none of which was considered related to AB122.

The trial continues to enroll patients for the every-three-week and every-four-week regimens to identify the appropriate doses. Also, Arcus is planning to start an expansion group in non-small cell lung cancer to confirm whether AB122 has similar clinical activity to that of the approved anti-PD-1 medications.

The research, “Preliminary results from an ongoing Phase 1 study of AB122, an anti-programmed cell death-1 (PD-1) monoclonal antibody, in patients with advanced solid tumors,” was recently presented at the 33rd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in Washington, D.C. Arcus will make the nine posters presented at SITC available on its website.

Ongoing Phase 1/1b trials are testing the combination of AB122 with AB928 — a dual blocker of A2A and A2B adenosine receptors (NCT03629756) — and with AB154, which targets a different T-cell protein called TIGIT (NCT03628677). Both trials are currently enrolling participants and preliminary data of the study on AB122 and AB928 are expected in the second quarter of 2019.

Terry Rosen, PhD, Arcus’ CEO, said that having an anti-PD-1 antibody to maximize the value of the company’s own product candidates guided Arcus’ decision to obtain a development and marketing license from WuXi Biologics, which originally developed AB122.