Despite the challenges brought with the coronavirus disease (COVID-19) pandemic, 2020 was another year of growth for the clinical trials program at Perlmutter Cancer Center with more than 100 new trials activated.

Combining Chemoradiation with Immunotherapy for Muscle-Invasive Bladder Cancer

Arjun V. Balar, MD, associate professor of medicine, director of the Genitourinary Medical Oncology Program, and medical director of the Clinical Trials Office at Perlmutter Cancer Center, leads a randomized phase 3 clinical trial testing the combination of chemoradiation and pembrolizumab to treat people with muscle-invasive bladder cancer (MIBC).

About one out of four people who get bladder cancer in the United States have MIBC. Chemoradiation is the standard of care for patients who are not candidates for surgery or who do not want to have a radical cystectomy.

The phase 3 study expands on an early phase trial Dr. Balar designed that tested the combination of chemoradiation and pembrolizumab as an alternative to cystectomy. That trial treated about 54 patients, and the preliminary findings were very promising, Dr. Balar says. Patients have done well, and the vast majority have effectively treated their bladder cancer while avoiding surgical removal of the bladder.

The new phase 3 trial tests chemoradiation alone versus chemoradiation plus immunotherapy to determine whether the combination definitively improves cure rates for MIBC. Perlmutter Cancer Center will be the lead site in the United States, with other sites planned to open around the world.

“Findings from this study, if positive, will establish a new standard of care for patients with muscle-invasive bladder cancer who don’t want their bladder removed,” says Dr. Balar, who chairs the scientific advisory committee for the trial.

New Treatments for Non-Small Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) recently approved Retevmo^™ (selpercatinib) as the first drug for the treatment of people with non-small cell lung cancer (NSCLC) whose tumors have alterations in the RET gene. Results from a phase 1/2 clinical trial of Retevmo^™, a selective and potent RET kinase inhibitor, were published on August 27 in the New England Journal of Medicine. Study co-author Vamsidhar Velcheti, MD, associate professor of medicine and director of the Thoracic Medical Oncology Program, led the study at Perlmutter Cancer Center, 1 of 84 sites around the world that participated in the trial.

In the first 105 consecutively enrolled patients with RET-positive NSCLC who had previously received at least platinum-based chemotherapy, the percentage with a measurable response was 64 percent. Among 39 previously untreated patients, the percentage with an objective response was 85 percent, with 90 percent of the responses ongoing at 6 months. Among 11 patients with measurable central nervous system metastasis at enrollment, the percentage with an objective intracranial response was 91 percent.

“The most exciting thing about this agent is that it can cross the blood–brain barrier, so we can actually use it to treat lung cancer that has metastasized to the brain,” says Dr. Velcheti.

Dr. Velcheti is currently conducting a phase 1/2 trial of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation. Conducted in collaboration with Mirati Pharmaceuticals, the trial is testing the hypothesis that combining the KRAS inhibitor MRTX849 with TNO155, an inhibitor of the protein tyrosine phosphatase SHP2, can overcome resistance in patients with KRAS G12C–positive lung cancer.

The trial is based on preclinical work from the lab of Benjamin G. Neel, MD, PhD, professor of medicine and director of Perlmutter Cancer Center, that demonstrated inhibiting SHP2 with KRAS signaling can augment responses to selective KRAS inhibitors.

“This is still an early phase 1 clinical trial, but the science behind it is absolutely fascinating, and we are very excited about it,” Dr. Velcheti says. “My hope is that if we demonstrate safety and if we have early signs of efficacy, this trial would expand to a larger phase 2 trial.”

Testing Antibody–Drug Conjugate in Women with Metastatic Breast Cancer

Yelena Novik, MD, associate professor of medicine, is lead investigator of a phase 3 clinical trial of the antibody–drug conjugate Immu-132, also known as sacituzumab govitecan-hziy, in women with hormone receptor–positive, HER2-negative metastatic breast cancer that has progressed after endocrine therapy as well as two lines of chemotherapy.

In April 2020, the FDA approved Immu-132 for the treatment of metastatic triple-negative breast cancer (TNBC). Because Immu-132 has been effective in treating TNBC, the current phase 3 trial, part of a multisite, international study, is testing the hypothesis that this drug might also be effective in breast cancers that used to be sensitive to hormonal therapy, Dr. Novik says.

Immu-132 combines the cancer drug SN-38 with a Trop2 antibody, which drags it specifically to an antigen frequently seen on cancer cells. Coupling SN-38, a topoisomerase inhibitor, with Trop2 enables targeted delivery of the chemotherapy with potentially fewer side effects.

“By using smarter drug delivery with potentially more effective delivery of the chemotherapy molecule to the tumor, we hope to improve the chances that a woman with metastatic breast cancer can live longer,” Dr. Novik says.

Adjuvant Study Targets Resected Melanoma

More than 20 active trials are underway investigating treatments for melanoma and skin cancers, says Jeffrey S. Weber, MD, PhD, the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine and deputy director of Perlmutter Cancer Center. Dr. Weber conducts the only adjuvant study in Manhattan for resected stage II and stage III melanoma.