Established 5 years ago, the Phase 1 Drug Development Program at NYU Langone Health’s Perlmutter Cancer Center has grown to offer nearly 40 phase 1 clinical trials, with 10 new trials since March 2019 that cover a wide array of drug strategies and tumor types.

“A cancer center that provides access to the most novel, cutting-edge therapies for its patients can enrich all the other disease groups,” says Daniel C. Cho, MD, associate professor in the Department of Medicine and director of the Phase 1 Drug Development Program. “For example, a successful phase 1 trial might lead to subsequent trials in lung cancer, melanoma, bladder cancer, and other diseases.”

A Novel Immunotherapy Drug with the Promise of Treating a Broad Range of Cancers

Immunotherapies comprise the bulk of phase 1 trials offered at Perlmutter Cancer Center, including a first-in-human clinical trial in solid tumors targeting the Siglec-15 pathway, an important immune suppressor in the PD-L1–null tumor microenvironment. This exciting trial is currently underway at Perlmutter Cancer Center and four other sites in the United States.

Agents targeting the PD1/PD-L1 immune checkpoint axis (or pathway) have revolutionized the treatment of melanoma and some other solid tumors. Unfortunately, with the exception of a fraction of melanomas, other solid tumors respond only transiently or not at all. Preclinical research by Jun Wang, PhD, assistant professor in the Department of Pathology, indicates that tumors with high levels of PD-L1 tend to have low Siglec-15 expression, whereas tumors low in PD-L1 tend to have high Siglec-15. Overall, only about 3 percent of tumors express both markers. Since patients with tumors high in PD-L1 tend to be the group that responds to PD1/PD-L1 inhibitors, a therapy that selectively targets the PD-L1–low population could significantly increase the number of patients who benefit from immunotherapy.

Targeting a Specific Mutation in KRAS

Perlmutter Cancer Center will be a site for several studies on a KRAS inhibitor that targets the so-called “G12C” mutation in KRAS, one of the most frequently mutated oncogenes in all cancer. This mutation accounts for 12 percent of all KRAS G12 mutations and 40 percent of KRAS mutations in non-small cell lung carcinomas.

“We have struggled to target KRAS since the advent of oncology, so having a drug that can be effective in the particular subset of this mutation is very exciting,” Dr. Cho says.

NKTR-214 Trial Leads to Later Phase Trials

One of the program’s more exciting studies, Dr. Cho says, is a phase 1 trial of an immunotherapy drug called NKTR-214, a novel “pegylated” version of IL-2, which is being studied in combination with nivolumab, as well as with ipilimumab and nivolumab, across several different tumor types. This novel approach, which combines an immune checkpoint inhibitor with a cytokine driver to deepen the response, has led to two phase 3 trials in melanoma and renal cancer and two phase 2 trials in lung and bladder cancer.

Karen Peterson, a patient with triple-negative breast cancer (TNBC), did exceedingly well with NKTR-214. Diagnosed with stage I disease in 2015, Ms. Peterson’s cancer became metastatic two years later. She identified an immunotherapy trial for breast cancer at Perlmutter Cancer Center and received a call from Dr. Cho, who suggested she wait for the NKTR-214 trial to open. After 20.7 months of treatment, Ms. Peterson reached maximum clinical benefit with a 100 percent reduction in her target tumors—and continues to show disease stability. This outcome has resulted in a planned phase 2 trial for NKTR-214 in TNBC.

Nearly all of the phase 1 trials are sponsored by pharmaceutical companies. However, Perlmutter Cancer Center is one of the lead sites on a UM1 application for an early therapeutics grant that would provide membership in the National Cancer Institute’s Experimental Therapeutics Clinical Trials Network (ET-CTN). ET-CTN membership, in turn, would provide grant support to conduct investigator-initiated trials under the auspices of the Cancer Therapy Evaluation Program.

“Drug development has evolved to the point where most trials are either phase 1 or phase 3, with fewer phase 2 trials than there used to be,” Dr. Cho says. “This grant presents an opportunity for cancer centers who devote resources to phase 1 studies to get involved early on and make a substantial and substantive impact on not just drug development but patient care.”

While growth in phase 1 trials has been substantial, Dr. Cho and Perlmutter Cancer Center leadership hope to continue to increase the size of the program as well as expand it to additional Perlmutter Cancer Center locations, including NYU Winthrop Hospital and NYU Langone Hospital—Brooklyn.