Immunotherapy, which has revolutionized the treatment of many types of cancer, is undergoing extensive study in patients with ovarian cancer. Although much of this research is in the early stages, it has produced some intriguing findings about the promise of this approach to treatment.
Clinical trials are exploring a variety of types and combinations of immunotherapy agents. Trials of immune checkpoint inhibitors — therapies that expose tumor cells to a potent immune system attack — have produced responses in about 10% of patients with advanced ovarian cancer. To improve on those results, researchers are pairing these agents with a range of drugs that may work together. Other forms of immunotherapy, including bispecific antibodies and therapeutic vaccines, are in early phases of clinical trials as well.
Examples of these approaches include:
One strategy is to combine checkpoint inhibitors with other agents. Examples of this approach include:
- A phase II clinical trial led by Dana-Farber’s Joyce Liu, MD, MPH, found that the checkpoint inhibitor nivolumab plus bevacizumab — an angiogenesis inhibitor that impedes tumors’ access to the bloodstream — was active in patients with relapsed ovarian cancer, particularly in those whose cancer responds to platinum-based chemotherapy.
- In another trial, Liu and her colleagues have evaluated the effectiveness of a combination of a checkpoint inhibitor, bevacizumab, and a PARP inhibitor (a drug that hampers cancer cells’ ability to repair damage to their DNA). Results from the trial will be presented early in 2021.
- In a trial led by Dana-Farber’s Panos Konstantinopoulos, MD, PhD, a combination of a checkpoint inhibitor and PARP inhibitor produced encouraging results in some patients.
- The Javelin 100 trial is testing the tandem of avelumab, a checkpoint inhibitor, with platinum-based chemotherapy in patients with stage III and IV epithelial ovarian cancer; and the IMagyn050 trial is testing a four-drug regimen of the checkpoint inhibitor atezolizumab, the chemotherapy drugs paclitaxel and carboplatin, and bevacizumab in patients with newly diagnosed stage III or IV ovarian cancer.
A relatively new form of therapy, bispecific antibodies are two-armed proteins that lock onto tumor cells with one arm and immune system T cells with the other, bringing the cells into close proximity. The convergence activates the T cells and promotes the destruction of the tumor cells.
- Liu is leading a clinical trial of a bispecific antibody that latches on to T cells and to a protein called MUC16 on ovarian cancer cells. The trial is evaluating the antibody alone and in combination with cemiplimab, an immune checkpoint inhibitor.
Therapeutic cancer vaccines work by “teaching” a patient’s immune system to recognize specific proteins, called antigens, on tumor cells and to attack cells displaying those antigens.
- Konstantinopoulos is leading a trial of a personalized neoantigen cancer vaccine for patients newly diagnosed with ovarian cancer. The vaccine is made by sending each patient’s surgically removed tumor tissue to a lab where the tumor cells are engineered to produce new antigens associated with cancer. Injected back into the patient, the neoantigen-bearing cells provoke a potent immune system attack on cancer cells in the body.
The number and diversity of immunotherapy trials for ovarian cancer is an indication of our determination to find new and more effective ways of treating this disease. A full list of the clinical trials of ovarian cancer therapies, including immunotherapies, at Dana-Farber can be found here.