Neon Therapeutics’ personalized neoantigen vaccine coupled with Bristol-Myers Squibb’s Opdivo kept cancer at bay longer than Opdivo alone in patients with lung cancer, bladder cancer and melanoma in a phase 1b study.
The data suggest that neoantigen vaccines could be one way to make checkpoint inhibitors like Opdivo—which have seen success in some cancers—work for more patients. Neon is just one of many companies working on agents to deliver alongside these drugs to improve their efficacy. Its approach harnesses neoantigens in a custom-made vaccine that helps the immune system launch an attack against cancer.
“Neoantigens are abnormal proteins that result from mutations and cancer is a set of diseases resulting from mutations … For a variety of reasons, the body is unable to mount an immune attack utilizing these targets to thwart cancer,” Neon Therapeutics CEO Hugh O’Dowd told FierceBiotech.
Neon sequences patients' tumors to identify neoantigens. Its lead program, NEO-PV-01, is made using synthetic peptides that mimic neoantigens found in each patient’s tumor cells. The idea is to “direct the immune system to these [neoantigen] targets to stimulate an immune attack against cancer in a targeted way, while leaving normal, healthy tissues alone,” O’Dowd said.
The topline data come from the NT-001 study involving 82 patients who had advanced or metastatic melanoma, non-small cell lung cancer (NSCLC) linked to smoking or bladder cancer. The patients entered the study at various points of cancer treatment—some had received no prior treatment, while others had undergone multiple lines of therapy—but none been treated with a checkpoint inhibitor. The majority of lung and bladder cancer patients had received prior treatment: 67% and 71%, respectively.
After at least one year of follow-up, the investigators found that the combination staved off cancer for a median of 5.6 months in 27 patients with metastatic lung cancer and 21 patients with bladder cancer, an improvement for both over historical data for checkpoint blockers alone. As for the 34 melanoma patients, they had not yet reached a median progression-free survival after more than 13 months of follow-up.
“We looked at a range of different trials using different checkpoint inhibitors with similar patient groups and found that in melanoma, progression-free survival with checkpoint monotherapy ranges from three to seven months, depending on whether the patient if first-line or later-line,” said Richard Gaynor, M.D., Neon’s president of R&D.
The historical data show that checkpoint inhibitors alone warded off bladder cancer for two to three months and NSCLC for two to four months.
"With these NT-001 results, we are observing consistent prolongation of progression-free survival across all three tumor types compared with historical checkpoint inhibitor monotherapy studies involving patients with similar baseline characteristics," said the study's lead investigator Patrick Ott, M.D. Ph.D., clinical director of the melanoma center at the Center for Immuno-Oncology at the Dana-Farber Cancer Institute, in a statement. "This is an exciting step in establishing the potential of neoantigen-based therapies as a vital component of the cancer treatment landscape."
“What we can say pretty confidently across all three groups of patients is that this combination of personal vaccine with checkpoint inhibitors improved outcomes versus the monotherapy checkpoint,” Gaynor said.
NEO-PV-01 is already in another phase 1b study with Merck's Keytruda and chemotherapy as a first-line treatment in patients with metastatic NSCLC, with data expected in the third quarter of 2020. Next up, Neon will start a phase 2 trial of the vaccine with a checkpoint blockade as a first-line treatment for metastatic melanoma.
“We foresee NEO-PV-01 being really applied in combinations in the frontline metastatic setting across a wide range of cell tumors, whereas we see NEO-PTC-01—our personal adoptive neoantigen T-cell product—positioned in the relapsed/refractor setting to checkpoint inhibitors,” O’Dowd said.
The different approaches allow Neon to “ask and answer unique questions to serve unique patient populations,” he said.
Editor's note: This story has been updated to clarify that Neon identifies neoantigens in patients' tumors and then uses synthetic peptides that mimic those neoantigens in its personalized cancer vaccine.