Arcus Biosciences and Genentech, a Roche company, are partnering on two clinical trials for colorectal and pancreatic cancer. They will evaluate Arcus’s AB928 in various combinations.

The first study will evaluate AB928 in third-line metastatic colorectal cancer. It will have two combination arms, the first AB928 and Roche’s Tecentriq (atezolizumab) and Bayer’s Stivarga (regorafenib), and the second, Stivarga and Tecentriq, all compared to Stivarga monotherapy.

The second trial will be in first-line metastatic pancreatic cancer. It will evaluate the combination of AB928 and Tecentriq and gemcitabine/nab-paclitaxel, a chemotherapeutic, compared to gemcitabine/nab-paclitaxel alone.

AB928 is a dual antagonist of adenosine receptors A2aR and A2bR. It is designed to block the immunosuppressive and cancer cell effects of adenosine.

“We are thrilled to collaborate with Genentech to expeditiously develop the broad potential of AB928 across settings and combinations where blocking the immunosuppressive role of adenosine may be critical,” said Bill Grossman, Arcus’ chief medical officer.

Grossman added, “This collaboration represents a shared commitment from Arcus and Genentech to maximize the potential of innovative combination treatment approaches, based on a deep knowledge of the underlying cancer biology, to address significant unmet needs.”

Specific finances were not disclosed. Each company is supplying its cancer drug and they are jointly funding the trials.

Arcus also announced the publication of the results of the Phase I trial of AB928 in healthy volunteers. The results were published in the journal Investigational New Drugs.

The study evaluated doses between 10 and 200 mg once a day and 100 mg twice a day and enrolled 85 patients. They were randomized 3:1. The drug was well tolerated up to the highest dose and did not demonstrate any physiologic parameters that might indicate sensitivity to adenosine inhibition. There were no safety concerns.

The company noted, “Adenosine is an immunosuppressive metabolite produced at high levels within the tumor microenvironment.”

The study authors wrote, “Clinical development continues with Phase I/Ib trials of AB928 in combination with other immunotherapy agents or chemotherapy in patients with breast or ovarian cancer, gastroesophageal or colorectal cancer, lung cancer, and advanced malignancies.”

Last week, Genentech announced Phase III results from a study of previously untreated BRAF V600 Mutation-positive advanced melanoma. The Phase III IMspire150 trial showed that Tecentriq with Cotellic (cobimetinib) and Zelboraf (vemurafenib) decreased the risk of disease worsening or death compared to placebo plus Cotellic and Zelboraf.

IMspire150 is a Phase III trial whose primary endpoint was investigator-assessed progression free survival (PFS). Key secondary endpoints included PFS by an independent review committee, overall survival, objective response rate, duration of response and various safety and pharmacokinetic data.

Tecentriq is being evaluated in more than 50 ongoing clinical trials, including multiple Phase III studies in lung, kidney, skin, breast, colorectal, prostate, ovarian, bladder, blood, liver and head and neck cancers.

“By combining a cancer immunotherapy with targeted therapies, we hope to offer a new approach that improves outcomes for people with advanced, BRAF-mutant melanoma,” said Levi Garraway, Genentech’s chief medical officer and head of Global Product Development. “We look forward to discussing the results with health authorities around the world.”

 

 

BioSpace source:

https://www.biospace.com/article/arcus-and-roche-partner-on-colorectal-and-pancreatic-cancer-trials