Alicia Kalogeropoulos, shown here with her husband, Alex, was diagnosed with low-grade glioma at age 27. Her team at MSK gave her the opportunity to participate in a clinical trial of the experimental drug vorasidenib. The drug halted the growth of her tumor with no side effects.
Doctors at Memorial Sloan Kettering Cancer Center (MSK) pioneered advances in a variety of cancer treatment for patients in 2023. The results from many cutting-edge clinical trials this year are leading to promising new treatments for brain cancer, colorectal cancer, bladder cancer, endometrial cancer, and several different blood cancers.
In addition, the Food and Drug Administration (FDA) approved seven drugs in 2023 based on clinical trials in which MSK played a pivotal role.
“We are living in a transformative age for cancer care, where advances in the lab are moving into the clinic faster than ever before,” says MSK President and CEO Selwyn M. Vickers, MD, FACS. “Across MSK, our doctors, scientists, and other staff are focused on developing precision therapies that are effective against cancer while preserving patients’ quality of life during and after cancer treatment.”
Here are some of the most important developments of 2023, listed in chronological order:
Off-the-Shelf CAR T Cell Therapy for Multiple Myeloma Shows Promise
One of the most advanced treatments for multiple myeloma is CAR T cell immunotherapy, but it can take a month or more to engineer customized immune cells for an individual patient. Now a new approach using donor cells brings the hope of giving off-the-shelf CAR T cell immunotherapy to patients in as little as five days. In a phase 1 clinical trial led by MSK multiple myeloma specialist Sham Mailankody, MBBS, patients were given CAR T cells already banked from other donors, as opposed to their own cells. The results, published in the January 23, 2023, issue of Nature Medicine, demonstrate that this type of CAR T cell donation can be safe and effective.
Testing CRISPR-Edited CAR T Cell Therapy in Lymphoma Clinical Trial
To make CAR T cell therapy even more precise and powerful, a clinical trial was launched at MSK testing CAR T cells that were made using a genome-editing tool called CRISPR/Cas9. This latest advance was made possible by the work of Michel Sadelain, MD, PhD, Director of the Center for Cell Engineering and the Gene Transfer and Gene Expression Laboratory at MSK, in collaboration with MSK’s Cell Therapy and Cell Engineering Facility. Investigators believe the phase 1 clinical trial, led by hematologic oncologist Jae Park, MD, has the potential to change the future of immunotherapy.
Menin Inhibitors: Promising New Drug Treatment for Aggressive Leukemia
Revumenib, a drug in a new class called menin inhibitors, was developed based on research conducted at MSK. It targets certain genetic changes that are commonly found in acute myeloid leukemia and acute lymphocytic leukemia. On March 15, 2023, MSK leukemia specialist and early drug development specialist Eytan Stein, MD, published results from the first-ever clinical trial of revumenib in Nature. More than half of patients with these molecular changes responded to the drug. Based on earlier data presented from this trial, the FDA had already granted revumenib Breakthrough Therapy Designation — indicating its potential over existing therapies to improve outcomes for patients.
For Advanced Endometrial Cancer, Chemotherapy Plus Immunotherapy Improves Outcomes
Endometrial cancer, which makes up about 90% of uterine cancers, is the fourth most common cancer in women and is one of the few cancers that is increasing in incidence and mortality. But until now, very few treatments have been developed specifically for endometrial cancer. Research published March 27, 2023, in The New England Journal of Medicine found that adding the immunotherapy drug pembrolizumab (Keytruda®) to standard chemotherapy greatly improves outcomes, whether or not patients had a genetic marker suggesting they were likely to respond to immunotherapy. The trial, which was also presented at the Society of Gynecologic Oncology’s annual meeting, was overseen by MSK physician-scientist Carol Aghajanian, MD.
For Advanced, HER2-Amplified Bile Duct Cancers, Antibody Treatment Trial Shows Promising Results
Bile duct cancers are rare, aggressive types of gastrointestinal cancer that are difficult to treat. Research published June 2 in The Lancet Oncology found an antibody treatment called zanidatamab helped shrink tumors in some patients with bile duct cancers — specifically, a subset of people whose tumors make a high amount of the HER2 protein, which can cause cells to multiply too quickly. The phase 2b clinical trial, which also was presented at the American Society of Clinical Oncology’s annual meeting, was co-led by MSK gastrointestinal oncologist James Harding, MD.
Rectal Cancer Treatment Without Radiation: A New Option
A large multicenter clinical trial presented at the American Society of Clinical Oncology’s annual meeting studied treating locally advanced rectal cancer without radiation. Researchers found that after five years, people who received a type of chemotherapy called FOLFOX before surgery did just as well as those who underwent both chemotherapy and radiation before surgery. Skipping radiation could mean improvements in quality of life, including the preservation of fertility, sexual function, and more. The study, which was also published in The New England Journal of Medicine on June 4, 2023, was led by gastrointestinal oncologist Deb Schrag, MD, MPH, Chair of MSK’s Department of Medicine.
Experimental Drug for Low-Grade Glioma With IDH Gene Mutation Shows Promise
Brain tumors are among the deadliest and most difficult cancers to treat. But a new experimental drug called vorasidenib has been shown to slow the growth of low-grade diffuse gliomas with a certain gene mutation called IDH. A phase 3 clinical trial of people with low-grade gliomas containing the mutation found that the drug significantly slowed tumor growth — more than doubling the time before the cancer began to progress compared with a placebo. Results from a clinical trial demonstrating the drug’s potential were presented at the American Society of Clinical Oncology’s annual meeting and published in The New England Journal of Medicine on June 4, 2023. Ingo Mellinghoff, MD, FACP, Chair of MSK’s Department of Neurology, led the research.
Preventing Lynch Syndrome Cancers: New Study Suggests Immunotherapy Could Work
An analysis of patients with an inherited condition called Lynch syndrome found that immunotherapy drugs called checkpoint inhibitors may stop serious tumors from forming, suggesting a possible approach for preventing cancer. Lynch syndrome results from a DNA mismatch repair deficiency, which is caused by a gene mutation that prevents cells from repairing genetic damage. The study found that people who received an immunotherapy drug for tumors due to Lynch syndrome had fewer additional tumors in their internal organs than did patients treated with chemotherapy. The corresponding author of the paper, published October 16, 2023, in Nature Medicine, was MSK gastrointestinal oncologist and clinical geneticist Zsofia Stadler, MD.
New mRNA Pancreatic Cancer Vaccine Trial Starts Next Phase
An experimental approach to treating pancreatic cancer — an mRNA vaccine — has progressed to a phase 2 clinical trial. The new trial follows a phase 1 trial involving 16 MSK patients, reported May 10, 2023, in Nature, which found that patients who mounted an immune response to the vaccine had longer recurrence-free survival. The new study will investigate whether the therapeutic vaccine reduces the risk of pancreatic cancer returning after the tumor is removed by surgery. It will enroll approximately 260 patients at MSK and other sites around the world and is being led by MSK pancreatic cancer surgeon-scientist Vinod Balachandran, MD.
The FDA Approves 7 Drugs in 2023 Based on Significant Contributions From MSK Investigators
These new therapies treat cancers of the breast, urinary system, blood, lung, and soft tissues.
- For certain people with advanced or metastatic breast cancer (stages 3 and 4), the FDA approved the drug therapy elacestrant (Orserdu™) on January 27. Elacestrant was effective in patients whose tumors were ER-positive, HER2-negative; had continued to grow after hormone therapy; and had a mutation in a gene called ESR1. The approval capped a decade of pivotal research led by MSK breast cancer specialist Sarat Chandarlapaty, MD, PhD.
- For people with metastatic urothelial carcinoma — a cancer that primarily arises in the bladder and also occurs in other parts of the urinary system — the FDA approved the drug enfortumab vedotin (Padcev®) plus the immunotherapy drug pembrolizumab (Keytruda®) for two different patient groups on April 3 and December 15. This greatly expands the number of people with bladder cancer who could benefit from these treatments. MSK genitourinary oncologist and bladder cancer specialist Jonathan Rosenberg, MD, led multiple clinical trials testing enfortumab vedotin alone or in combination with other drugs.
- For adults with previously untreated diffuse large B cell lymphoma, the FDA approved the drug polatuzumab vedotin (Polivy®) in combination with rituximab, cyclophosphamide, doxorubicin hydrochloride, and prednisone as a first-line therapy for adults with previously untreated diffuse large B cell lymphoma. This was the first new drug approval in this clinical setting in 20 years. It was based on the results of a study conducted in the United States and Europe. MSK’s Lymphoma Service, led by lymphoma specialist and cellular therapist Gilles Salles, MD, PhD, treated the most U.S. patients in the trial.
- For resistant forms of multiple myeloma, a rare blood cancer that can be difficult to treat, the FDA granted accelerated approval to elranatamab (Elrexfio™) on August 14. Elranatamab is a type of drug known as a bispecific antibody. It targets a protein on myeloma cells called BCMA, as well as a protein on the immune system’s T cells called CD3. MSK myeloma specialist and cellular therapist Alexander M. Lesokhin, MD, led the development and testing of this drug.
- For people with metastatic non-small cell lung cancer with a BRAF V600E mutation, the FDA approved a combination of the targeted drugs encorafenib (Braftovi®) and binimetinib (Mektovi®) on October 11. The combination of the drugs, which are both taken as pills, was already approved for some people with melanoma. The new approval was based on a multicenter phase 2 clinical trial led by MSK thoracic oncologists Gregory Riely, MD, PhD, and Michael Offin, MD.
- For the treatment of locally advanced or metastatic non–small cell lung cancer caused by a mutation called a ROS1 fusion, the FDA granted approval to repotrectinib (Augtyro™) on November 15. The drug appears to be effective even in patients who have developed resistance to other ROS1 inhibitors. The approval was based on results from a phase 1/2 trial led by MSK thoracic oncologist and early drug development specialist Alexander Drilon, MD.
- For adults with desmoid tumors that cannot be treated with surgery alone, the FDA granted approval to the drug nirogacestat (Ogsiveo™) on November 27. The approval was based on research led by investigators at MSK, including sarcoma expert Mrinal Gounder, MD. Nirogacestat is the first targeted therapy ever to be approved for desmoid tumors (also known as aggressive fibromatosis), a type of soft-tissue tumor.