Arcus Biosciences, Inc. (NYSE:RCUS) and Infinity Pharmaceuticals, Inc. (NASDAQ:INFI) announced on 6/26/2018 that they have entered into a clinical collaboration to evaluate two triple combination therapies in selected tumor types which typically show minimal response to checkpoint inhibition monotherapy.
The collaboration will evaluate IPI-549 in combination with AB928, Arcus’s dual adenosine receptor antagonist, and AB122, Arcus’s anti-PD-1 antibody, as well as IPI-549 in combination with AB928 and chemotherapy in patients with triple negative breast cancer (TNBC) or ovarian cancer in four separate cohorts. These four cohorts will be incorporated into Arcus’s recently initiated Phase 1/1b trial to evaluate AB928 combinations in TNBC and ovarian cancer. As both macrophages and high adenosine levels are believed to play critical roles in creating a highly immune-suppressive tumor microenvironment in TNBC and ovarian cancer, the triple combinations being evaluated could represent a promising approach to treating these tumor types. By intervening in multiple mechanisms that mediate immuno-suppression, the companies hope to address two tumor types that lack effective therapies, particularly in later lines of treatment.
“This partnership with Infinity is important as, for the first time, we will be investigating the potential for the triple combination of a selective PI3K-gamma inhibitor, a dual adenosine receptor antagonist, and either a PD-1 inhibitor or chemotherapy to effectively treat patients with triple negative breast cancer or ovarian cancer,” said Terry Rosen, Ph.D., Chief Executive Officer of Arcus Biosciences. “This collaboration also allows us to expand the number of promising combinations with strong biological rationale that we plan to evaluate in our recently initiated Phase 1/1b trial for AB928. Arcus has carefully considered which immuno-oncology therapies can best target immune suppressive macrophages and has concluded that selective inhibition of PI3K-gamma is a fundamental mechanism for reprogramming macrophages from a pro-tumor to an anti-tumor function.”
“This collaboration with Arcus Biosciences enables an important expansion of our clinical development of IPI-549, investigating IPI-549 in triple-combination therapy with other important immuno-oncology agents as well as with chemotherapy,” said Adelene Perkins, Chief Executive Officer and Chair of Infinity Pharmaceuticals. “Combining these agents may result in enhanced reduction of pro-tumor immune suppression and increased anti-tumor immune activation. We look forward to working with the terrific team at Arcus in investigating these triple-combination therapies as potentially new treatment options for patients with cancers that are not adequately addressed by existing therapies.”
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. AB928 is in Ph I trials.
IPI-549 is an investigational first-in-class, oral, immuno-oncology product candidate targeting tumor-associated myeloid cells through selective phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibition, thereby reducing pro-tumor macrophage function and increasing anti-tumor macrophage function. In preclinical studies, IPI-549 demonstrated the ability to reprogram macrophages from a pro-tumor (M2), immune-suppressive function, to an anti-tumor (M1) immune-activating function and enhance the activity of, and overcome resistance to, checkpoint inhibitors. IPI-549 is currently in Ph I/Ib trials.