NC318 Plus Keytruda Shows Promise in Pretreated Lung Cancer

A combination of the novel drug, NC318 plus the immunotherapy agent, Keytruda (pembrolizumab), demonstrated a clinical benefit in patients with advanced non-small cell lung cancer (NSCLC) that progressed on or after a PD-1 axis inhibitor, according to findings from an ongoing phase 2 study announced by NextCure, the manufacturer of NC318.

The ongoing trial is evaluating NC318 alone or in combination with Keytruda in 141 patients with pretreated NSCLC. In the two-drug portion of the study that included 18 patients with pretreated NSCLC, findings showed that 28% of patients experienced a durable clinical benefit (disease shrinking or disease that stopped growing for six months or more), including three patients experiencing a confirmed response, meaning that their disease shrunk.

All confirmed responses were observed in patients with PD-L1—negative tumors, meaning that their cancer cells had little to no expression of the PD-L1 protein. However, according to a press release issued by NextCure, patients benefitted from the treatment regardless of their PD-L1 status.

NC318 is a monoclonal antibody that blocks the interactions of the S15 protein and myeloid cells and T lymphocytes (immune cells) within the tumor microenvironment. By doing so, it blocks the inhibitory signaling that would otherwise stop T cells from finding and attacking cancer. Similarly, Keytruda blocks the PD-1 pathway, which also helps cancer cells hide from the immune system.

“We are excited that this investigator-initiated trial, part of our NCI Lung SPORE (Specialized Program of Research Excellence), is providing new insights into the mechanisms and treatment of immune therapy resistance. We look forward to reporting more data in the future,” said Dr. Roy Herbst, Ensign professor of medicine (medical oncology) and professor of pharmacology; deputy director, Yale Cancer Center; chief of medical oncology, Yale Cancer Center and Smilow Cancer Hospital; assistant dean for Translational Research, Yale School of Medicine; director, Center for Thoracic Cancers, Yale Cancer Center and Smilow Cancer Hospital, said in a press release.

So far, treatment with NC318 has been well tolerated — both in the combination and single-agent setting — according to the press release. The most common moderate (grade 3) side effects observed in the trial were: transverse myelitis (spinal cord inflammation), infusion reactions, rash and pneumonitis (inflammation of the lungs). Less severe (grade 2) side effects observed were infusion reactions, pericarditis (inflammation around the heart) and psoriasis (itchy, scaly skin patches).

The phase 2 trial is still ongoing, with an estimated study completion date of June 2025, according to the study’s listing on clinicaltrials.gov.

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