Arcus Biosciences and Infinity Pharmaceuticals have entered into a clinical collaboration to evaluate two triple combination therapies in certain 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.
Arcus Biosciences CEO Terry Rosen said: "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.
"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."
Infinity Pharmaceuticals CEO and chair Adelene Perkins said: "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.
"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."
Under the terms of the agreement, Infinity and Arcus will share equally expenses related to the four triple-combination cohorts to evaluate the safety and activity of IPI-549 + AB928 + AB122 and IPI-549 + AB928 + chemotherapy.
Each of the four triple-combination cohorts will enroll approximately 15 patients. Topline data from these studies are expected in 2019.
Source: Company Press Release