Researchers have made significant advances in the treatment of cancer, enabling people to live longer with a better quality of life. In 2021, the U.S. Food and Drug Administration (FDA) granted approval for numerous novel drugs. Clinical trials conducted at NYU Langone Health’s Perlmutter Cancer Center played a role in generating data that led to the FDA’s approval of new treatments for people with bladder cancer, non-small cell lung cancer (NSCLC), endometrial cancer, and melanoma.
“Clinical trials are important because they are often the first way people can get access to a lifesaving drug before that drug gets to the market,” says Janice Mehnert, MD, professor in the Department of Medicine at NYU Grossman School of Medicine and associate director for clinical research at Perlmutter Cancer Center.
Antibody–Drug Conjugates for Metastatic Bladder Cancer
Antibody–drug conjugates, which can deliver cancer-killing drugs directly to a tumor without harming healthy adjacent cells, are becoming an important tool for treating cancer. In 2021, two of these innovative agents were approved for people with metastatic bladder cancer.
On April 13, sacituzumab govitecan (Trodelvy) received accelerated approval for patients with locally advanced or metastatic bladder cancer who previously received a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor. Sacituzumab govitecan couples a cancer drug called SN-38 with a Trop2 antibody that targets an antigen frequently seen on cancer cells.
On July 9, enfortumab vedotin (Padcev) was approved for adults with locally advanced or metastatic bladder cancer who have previously received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy. It also was approved for patients who are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy. Enfortumab vedotin carries a tumor-killing drug called monomethyl auristatin E (MMAE) linked to an antibody that targets Nectin-4, a receptor found on the surface of many cancer cells, but particularly in bladder cancer.
Both trials were led at Perlmutter Cancer Center by the Genitourinary Disease Management Group.
“These novel medications are now another weapon in the armamentarium for treating metastatic bladder cancer that otherwise would be rapidly progressive and fatal,” says Gary D. Steinberg, MD, director of the Goldstein Urology Bladder Cancer Program at Perlmutter Cancer Center.
Dr. Steinberg, who was not directly involved in the two trials that led to FDA approval, is leading a phase 1 clinical trial at Perlmutter Cancer Center that is testing enfortumab vedotin as an intravesical medication for people with high-risk, non–muscle-invasive bladder cancer that has recurred despite treatment with intravesical Bacillus Calmette-Guérin.
“Antibody–drug conjugates are changing the way we manage metastatic bladder cancer and are moving the field forward and helping these patients live longer,” says Dr. Steinberg, professor in the Department of Urology at NYU Grossman School of Medicine. “I personally know a number of patients who have responded very well to these medications.”
Targeted Therapies for Non-Small Cell Lung Cancer
In May 2021, two drugs were approved for NSCLC. On May 21, accelerated approval was granted to amivantamab (Rybrevant) for adults with locally advanced or metastatic NSCLC and EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Joshua K. Sabari, MD, assistant professor in the Department of Medicine at NYU Grossman School of Medicine, was the principal investigator at Perlmutter Cancer Center for this phase 1, first-in-humans clinical trial.
There have been many advances in targeted therapy development that have allowed people to live longer and better with stage 4 lung cancer, Dr. Sabari notes. Mutations in the EGFR gene in exon 19 and 21 are quite common, and there are FDA-approved matched targeted therapies with excellent activity and safety profiles. EGFR exon 20 insertion mutations are far less common, and until recently there have been no approved agents for patients with this alteration.
“Amivantamab is the first FDA-approved therapy for people with an EGFR exon 20 insertion mutation and is an important step forward for patients with this alteration,” Dr. Sabari says. “More work is needed to better understand resistance as well as central nervous system activity of these and other agents.”
On May 28, sotorasib (Lumakras) was approved as the first treatment for adult patients with NSCLC whose tumors have a KRAS-G12C mutation and who have received at least one prior systemic therapy. Vamsidhar Velcheti, MD, associate professor in the Department of Medicine at NYU Grossman School of Medicine and director of the Thoracic Medical Oncology Program at Perlmutter Cancer Center, was the principal investigator of the phase 1/2 trial.
Sotorasib inhibits KRAS-G12C, preventing cancer cells from growing. This allele is the most frequently seen mutation in NSCLC, and accounts for a significant percentage of KRAS mutants in colorectal cancer.
“Sotorasib is the first-of-its-kind treatment option for people with NSCLC tumors with KRAS-G12C mutations,” Dr. Velcheti says. “We now have a drug that is FDA-approved, effective, and much better tolerated than chemotherapy.”
Checkpoint Inhibitor for Advanced Endometrial Cancer
On April 22, dostarlimab (Jemperli), a checkpoint inhibitor, was granted accelerated approval for adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen. Bhavana Pothuri, MD, professor in the Departments of Obstetrics and Gynecology and Medicine at NYU Grossman School of Medicine and director of gynecologic oncology clinical trials at Perlmutter Cancer Center, was principal investigator of this phase 1 trial.
“Patients with advanced or recurrent endometrial cancer represent a true unmet need; we don’t have many other active therapies,” Dr. Pothuri says. “Dostarlimab’s approval is important in terms of having agents for the treatment of advanced endometrial cancer and represents a real win for our patients with endometrial cancer.”
First Approved Therapy for Stage 2 Melanoma
On December 3, the checkpoint inhibitor pembrolizumab (Keytruda) was approved for the adjuvant treatment of adult and pediatric (12 years of age and older) patients with stage 2B or 2C melanoma following complete resection. Dr. Mehnert has served as the principal investigator of this phase 3 study.
The standard of care for completely resected stage 2 melanoma was observation—not adjuvant therapy—and patients with stage 2B and 2C melanoma are at the same risk of disease recurrence and death as those with stage 3A and 3B melanoma. The results of the trial suggest that pembrolizumab as adjuvant therapy should be the new standard of care for stage 2 melanoma.
“This is the first time we have an approved therapy for patients with stage 2 disease,” Dr. Mehnert says. “Now, we need a better understanding of which patients will benefit from this therapy based on biomarker identification.”
Choosing to Join a Clinical Trial at Perlmutter Cancer Center
The decision to participate in a clinical trial can be a difficult one for patients, but there are circumstances where a patient might consider enrolling. For example, clinical trials can be an option for people who have not benefited from multiple lines of therapy. Dr. Mehnert notes that once a trial has advanced to phase 2 or 3, there is a battery of evidence behind it that shows the promise.
“The drugs we have discussed above, in fact, wound up being very successful,” Dr. Mehnert says. “It was certainly an advantage for our patients that we were able to offer those trials before the drugs were approved.”
Dr. Mehnert notes that people who need cancer treatment have excellent options to choose from in the New York City area. What sets Perlmutter Cancer Center apart, she says, is its mission to meet patients where they are with research. The cancer center’s clinical trials portfolio is designed to meet the needs of patients, considering that cancer does not travel well, and patients want to receive treatment closer to home. The expansion of clinical trial options in Brooklyn and on Long Island is part of this process. Dr. Mehnert also cites the patient experience at Perlmutter Cancer Center as an advantage.
“We try to do whatever we can to cater to the patient experience, which at Perlmutter Cancer Center is excellent,” Dr. Mehnert says. “The staff is engaged, and everybody here tries to go the extra mile to help our patients. And that is not something that is found everywhere.”