First-line treatment for pancreatic cancer! CD73 inhibitor AB680 plus chemotherapy and anti-PD-1 therapy has strong efficacy: total remission rate of 41%, disease control rate of 85%!

January 16, 2021 // -- Arcus Biosciences is a biopharmaceutical company focused on oncology dedicated to creating best-in-class cancer therapies.
, the company released preliminary data on the increased dose of ARC-8 in the AB680 therapeutic metastatic pancreatic cancer phase I/Ib study at the 2021 American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCO GI).
AB680 is the first small molecule CD73 inhibitor to enter the clinic.
data show that, to date, the objective remission rate (ORR) of AB680 therapy has been 41% in the first four treatment queues in the increased dose portion of the ARC-8 study, showing superiority over current standard care options.
(results detailed in: ARC-8: Phase 1/1b Study to Evaluate Safety and Tolerability of AB680 , Between and Zimberelimab (AB122) in Patients Treatment with-Naive Metastatic Pancreatic Adenocarcinoma AB68 0 (Photo source: tsbiochem.com) AB680 is an ultra-powerful, selective small molecule CD73 inhibitor designed to provide benefits different from monoclonal antibodies, such as stronger inhibition of CD73 enzyme activity (soluble and cell-binding) and deeper tumor penetration.
CD73 is the main enzyme that generates immunosuppressive adenosine in tumor microenviron environment, which converts single adenosine monophosphate (AMP) into adenosine, thus forming immunosuppression in tumor microenviron environment.
high expression of CD73 was associated with significantly poor prognosmology of a variety of tumor types, including pancreatic cancer.
By effectively eliminating Adenosine derived from CD73, AB680 can improve the efficacy of treatments that are expected to cause an anti-cancer immune response (e.g., platinum chemotherapy programmes based on combination/unlinked anti-PD-1 therapy).
AB680 showed good safety and a longer half-life in a healthy volunteer study.
, AB680 is currently undergoing phase I/Ib studies for the first-line treatment of metastatic pancreatic cancer.
ARC-8 is an open-label, multi-center Phase I/Ib clinical trial that is evaluating the safety and clinical activity of AB680 combined nab-yew alcohol and gisithamine (NP/Gem) and zimberelimab (AB122, an anti-PD-1 antibody) for first-line treatment in patients with metastatic pancreatic catheter adenocarcinoma (PDAC).
safety results (safe DCO as of November 11, 2020): 19 patients received AB680-NP/Gem-zimberelimab, and AB680 was given a dose range of 25-100 mg every 2 weeks.
in all four dose incremental queues, no significant overlay toxicity of AB680-NP/Gem-zimberelimab was observed to exceed the expectation of NP/Gem-anti-PD-1 combined medication.
A case of dose-limiting toxicity (level 2 autoimmune hepatitis) occurred in the 50mg AB680 queue;
most common adverse therapeutic reactions (AEs) were fatigue (68 per cent), anemia (53 per cent), hair loss (42 per cent), diarrhoea (42 per cent) and decreased neutral granulocyte count (42 per cent).
results are very similar to the expected results of using NP/Gem alone.
no other dose-limiting toxicity has been reported since the safety of DCO.
Preliminary Efficacy Results (DCO as of December 9, 2020): Of the 19 patients in the phase I dose incremental part of the group, 17 patients were assessed for efficacy, 16 of whom were still receiving treatment at the time of the efficacy assessment.
data show that 88% of patients (n-15/17) experienced at least some lesions.
in all dose incremental queues, ORR for AB680 codes was observed at 41% (7/17), with one patient achieving complete remission (CR).
for patients treated for more than 16 weeks, the disease control rate (DCR) of AB680 co-medication was 85% (n-11/13).
treatment benefits seemed to be long-lasting: 10 out of 12 (83%) of the assessable patients in the first three dose-incremental queues continued treatment, with a medium treatment time of 180 days.
in pancreatic cancer, the last drug approved for first-line treatment of metastatic pancreatic cancer is abraxane (nab-yew alcohol).
as the FDA-approved label for the first-line treatment of metastatic pancreatic cancer by Abraxane and Gissinabin states, the ORR registered for Phase 3 studies is 23% and the DCR is 48% (>16 weeks).
Bill Grossman, chief medical officer of Arcus, said:
A 100mg dose of AB680 has been selected every 2 weeks as the dose of the extended phase 1b of the trial, based on the results to date.
in view of the fact that the toxicity observed so far with the addition of AB680 to chemotherapy and anti-PD-1 treatment has not increased, we are also evaluating a 125 mg dose every 2 weeks in a queue.
believe AB680 has the potential to represent the first meaningful advance in pancreatic cancer treatment since Abraxane was approved in 2013.
Origin: Arcus Biosciences Presents Proy Initial Data from Phase 1 Part of ARC-8 Study for AB680 in Metastatic Pancreatic Cancer