AstraZeneca has struck a deal to combine its anti-PD-L1 drug with NewLink Genetics’ IDO pathway inhibitor. The collaborators will jointly fund a phase 2 trial of the combination in pancreatic cancer patients.
NewLink will sponsor the randomized, placebo-controlled metastatic pancreatic cancer phase 2. The study will assess the effect of adding a combination of AstraZeneca’s Imfinzi and NewLink’s indoximod to the standard-of-care chemotherapy regimen, Abraxane and gemcitabine. The trial will also feature a small cohort of patients who receive just Imfinzi and chemotherapy.
The study gives NewLink a chance to show its IDO inhibitor is complementary to PD-1/PD-L1 drugs in another indication, while also providing AstraZeneca’s laggard checkpoint inhibitor with a new opportunity.
“As recent data have indicated, indoximod combinations with immunotherapy and chemotherapy show promise of improving outcomes for patients with multiple tumor types,” NewLink CEO Charles Link, Jr., M.D., said in a statement.
PD-1-IDO combinations have generated the most excitement to date in melanoma. Incyte has early clinical data suggesting the combination of its IDO inhibitor epacadostat and Keytruda may deliver better outcomes than PD-1-CTLA-4 cocktails in advanced melanoma patients. NewLink is plugging away at the indication, too, most notably through a phase 2 trial that has teed it up to move into a pivotal study that will test indoximod in combination with Keytruda or Opdivo.
The thinking behind testing the combination in pancreatic cancer mirrors that which has driven progress in melanoma. IDO is an immune modulator that helps tumor cells escape the attention of the immune system. Disrupting the pathway could therefore limit the evasiveness of tumors, enabling checkpoint inhibitors to orchestrate full-force attacks against cancer cells.
NewLink has some clinical data suggesting the concept will work in pancreatic cancer patients. An interim analysis of a phase 1/2 trial of indoximod plus chemotherapy linked the regimen to a 37% overall response rate. That compares to the 23% achieved in a separate trial of the chemotherapy combination, although that was in a larger trial and study-to-study comparisons don’t necessarily reflect differences in efficacy.