AACR21 roundup: Arcus rolls out PhI data on adenosine blocker for CRC; Codiak's engineered exosome for IL-12 shows early promise
Arcus Biosciences’ adenosine blocker etrumadenant showed some benefit in extending patients’ lives as part of a Phase I/Ib trial in third-line-or-later colorectal cancer patients, according to data presented Saturday at the virtual AACR annual meeting.
Etrumadenant, a dual adenosine A2aR/A2b receptor antagonist, is designed to inhibit adenosine’s role in preventing lympocytes like CD8+ effector T cells and NK cells from infiltrating the tumor microenvironment, the company said. A combination of etrumadenant and chemotherapy regimen FOLFOX-6 posted a median PFS of 4.2 months, a median OS of 13.6 months and an objective response rate of 9.1%. The drug showed consistent benefits in BRAF/RAS mutated cancer cells, the company said.
The ARC-3 study wasn’t powered to compare that combination against placebo so it’s hard to know exactly what significance these results hold. But Arcus did highlight that patients on two established standards of care in that late-line setting reported a median PFS of 2 and 1 months, a median OS of 7.1 and 6.4 months and ORR of 1.6% and 1%, respectively. The study also showed that patients with high tumoral mutation burden and expression of CD73 within the tumor posted improved outcomes.
The results are promising enough that Arcus plans to advance etrumadenant into a Phase II/IIb study dubbed ARC-9 that will evaluate the drug in combination with the biotech’s anti-PD-1 antibody zimberelimab and FOLFOX with or without bevacizumab in second- and third-line metastatic colorectal cancer.
Codiak ekes out some early promise for its engineered exosome for IL-12
Codiak Biosciences is chasing a whole new class of drugs using engineered exosomes, and now it has super early human data it says may eventually provide proof of concept there.
Codiak’s exoIL-12, an exosome engineered to present IL-12 on its surface and attack tumors with a limited dose, posted new pharmacodynamic data at AACR showing no systemic production of interferon gamma, a byproduct of IL-12 activation associated with serious side effects. Those data are part of a randomized, placebo-controlled Phase I study Codiak is running in healthy volunteers.
Earlier results showed no systemic exposure to IL-12 and no site or systemic treatment-related adverse events. A 6-nanogram dose of the drug was present in the skin 24 hours after treatment, which Codiak believes could lasting IL-12 pathway activation. The drugmaker will take that dose into an expanded Phase II trial.
Hookipa touts early T cell boost for HPV cancer immunotherapies
Hookipa’s T cell immunotherapy candidates posted early immunogenicity wins as part of a Phase I trial targeting HPV16+ tumor types, the company said.
Candidates HB-201 and HB-202 drove an increase in HPV16-specific T cells, including an 8% jump in circulating CD8+ effector T cells after a single dose. HB-201 uses a single arenavirus vector while HB-202 employs two vectors, but both express the same antigen, an E7E6 fusion protein derived from HPV16.
The results come as part of a Phase I/II dose-escalation study trying HB-201 as a monotherapy, as part of an alternating regimen with HB-202 and in combination with a PD-1 blocker.