Alpine Immune Sciences turned heads a year ago when AbbVie formed a deal with the company worth up to $805 million in milestone payments for a first-in-class lupus drug that inhibits a protein on the immune system’s T cells called CD28. But the company is also pursuing one strategy for stimulating CD28 to improve the immune response to cancer—and it has early evidence its plan may be working.
Alpine presented initial data from an ongoing phase 1 trial of its immuno-oncology candidate ALPN-202, a CD28 costimulator, during the American Society of Clinical Oncology (ASCO) virtual annual meeting. The treatment was well tolerated, Alpine said, and 61% of the 23 patients who were able to be evaluated derived some clinical benefit, which the company defined as stable disease or better.
By binding CD28, ALPN-202 primes T cells for activation. The drug also binds to and antagonizes the immune checkpoints CTLA-4 and PD-L1, freeing up the immune system to attack cancer, the company explained during the ASCO presentation.
The 32 participants in Alpine’s phase 1 study of ALPN-202 have a variety of tumor types, including pancreatic, colorectal and uterine cancers. The patients had “generally received many prior lines of therapy” before enrolling in the trial, though few had received immunotherapy, said Stanford Peng, M.D. Ph.D., president and head of R&D at Alpine, during the ASCO presentation.
The company’s analysis of the patients in the trial found several markers of immune stimulation, including a proliferation of beneficial memory T cells and downregulation of regulatory T cells, which can suppress immune activity.
“Most of the participants enrolled in the study had tumors traditionally considered unresponsive to immunotherapy,” Peng said. “Nonetheless, evidence of clinical benefit appears to be present at this early stage.”
Alpine is not the only company pursuing CD28-targeted therapies in immuno-oncology. Regeneron is working on several CD28 costimulatory bispecific antibodies, which it has explored in combination with its PD-1 inhibitor Libtayo. Last year, Regeneron reported 70.8% survival in a mouse model of colon cancer for a bispecific targeting PSMA and CD28 combined with PD-1 blockade. That was a significant improvement over either the bispecific or the anti-PD-1 drug alone.
Targeting CD28 has proven challenging, however, because of safety concerns. Some patients in early clinical trials suffered the severe inflammatory reaction cytokine release syndrome, prompting developers to shelve CD28-targeted drugs.
Alpine said during ASCO that none of the participants in its phase 1 trial experienced cytokine release syndrome. Half of participants did have side effects, most of which were skin conditions such as rashes, the company said.
The phase 1 study will continue for the rest of the year, after which Alpine will choose the tumor types to be included for further study in an expansion trial. The company is also planning to launch a trial of the drug in combination with a PD-1 inhibitor, Peng said.