Ovarian Cancer Immunotherapy

Ovarian Cancer

Ovarian cancer is one of the major cancer types for which powerful, immune-based cancer treatments are now in development. This page features information on ovarian cancer and immunotherapy clinical trials for ovarian cancer patients, and highlights the Cancer Research Institute’s role in working to bring effective immune-based cancer treatments to ovarian cancer patients.

Ovarian cancer is the leading cause of death from gynecologic cancer in the United States. Each year nearly 22,280 women in the United States will be diagnosed with ovarian cancer, and 14,240 will die. Ovarian cancer is sometimes called “the cancer that whispers,” because the disease often progresses before symptoms arise. Nine out of 10 ovarian cancers are epithelial ovarian cancers— deriving from the outer (epithelial) layer of the ovary.

The most important risk factor for ovarian cancer is a strong family history of breast or ovarian cancer. Women who have had breast cancer or who have tested positive for inherited mutations in BRCA1 or BRCA2 genes are at increased risk.

Despite advances in surgery and chemotherapy over the past 20 years, only modest progress has been made in improving overall survival in patients with ovarian cancer. Although the majority of women with advanced ovarian cancer respond to first-line chemotherapy, most responses are not durable. More than 80% of patients will have a recurrence of their disease after first-line treatment, and more than half will die of recurrent disease within 5 years of diagnosis.

The poor survival in advanced ovarian cancer is due both to late diagnosis, as well as to the lack of effective second-line therapy for patients who relapse. The clinical course of ovarian cancer patients is marked by periods of remission and relapse of sequentially shortening duration until chemotherapy resistance develops. Therefore, new treatment modalities and paradigms are needed in order to significantly improve the prognosis of women diagnosed with epithelial ovarian cancer.

Treatment

First-line treatment for ovarian cancer includes surgery followed by a chemotherapy regimen combining a platinum-based (usually carboplatin) and a taxane-based (usually paclitaxel) treatment, which achieves a complete response in approximately 80% of patients. (A complete response means no visible evidence of disease on imaging scans and normal blood tests.) Patients who respond but who relapse after a period of six months or more may undergo the same therapy. Patients who progress during first-line treatment or who relapse within six months following successful first-line treatment are considered refractory or resistant to platinum-based treatments. For these patients, there are several chemotherapeutic options; however, each has shown only marginal benefit. Therefore, patients with platinum-resistant disease are encouraged to enter clinical trials.

When Should Ovarian Cancer Patients Consider a Clinical Trial? 

Women with stage 1, grade 1 tumors (in whom survival is greater than 95% after comprehensive surgery), do not generally need to consider clinical trials. Patients in all other stages of ovarian cancer are encouraged to enter clinical trials for both primary and recurrence therapy. Specifically, clinical trials may be recommended for the following:

  • Patients with stage 2, 3, and 4 ovarian cancer who are in complete remission after first-line treatment;
  • If cancer doesn’t respond to or progresses during first-line treatment;
  • Cancer recurs within 6 months of first-line treatment after complete remission;
  • Cancer that is stage 2, 3, or 4 and only partly responds to chemotherapy (“partly shrunk”);
  • Cancer recurs more than 6 months after complete remission with first-line chemotherapy;
  • Cancer responds to second or subsequent lines of chemotherapy, and the patient is in remission;
  • Cancer responds to second or subsequent lines of chemotherapy, but recurs again.

A number of immune-based therapies are being investigated in early-phase clinical trials for patients with ovarian cancer. Go to our Cancer Immunotherapy Clinical Trial Finder to find clinical trials of immunotherapies for ovarian cancer that are currently enrolling patients.

Immunotherapy For Ovarian Cancer 

Current immunotherapies for ovarian cancer fall into six broad categories: monoclonal antibodies; checkpoint inhibitors and immune modulators; therapeutic vaccines; adoptive T cell transfer; oncolytic viruses; and adjuvant immunotherapies. Most of these therapies are still in early-phase testing (phase I and II) for ovarian cancer, but their successful use in other types of cancers suggests that they may ultimately prove useful for ovarian cancer as well.

Monoclonal Antibodies

Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors. Bevacizumab (Avastin®), which targets vascular endothelial growth factor (VEGF), is FDA-approved for the treatment of ovarian cancer. Several monoclonal antibodies are currently being tested in clinical trials:

  • A phase II trial of farletuzumab that targets folate receptor alpha, which is highly expressed in ovarian cancer, in patients with low CA-125 platinum-sensitive ovarian cancer (NCT02289950).
  • A phase II study of mirvetuximab soravtansine (IMGN853) in patients with folate receptor alpha-positive advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer (NCT02631876).
  • A phase I study of mirvetuximab soravtansine (IMGN853) in patients with folate receptor alpha-positive advanced ovarian, primary peritoneal, or fallopian tube cancer (NCT02606305).
  • A phase I trial of mirvetuximab soravtansine (IMGN853) in patients with ovarian cancer that expresses folate receptor alpha (NCT01609556).
  • A phase I/II trial testing IMMU-132, an antibody-drug conjugate targeting Τrop-2, in patients with epithelial cancers (NCT01631552).
  • A phase I trial of DNIB0600A, an antibody conjugated to the anti-mitotic agent MMAE, for patients with platinum-resistant ovarian cancer (NCT01363947).
  • A phase I trial of DNIB0600A for patients with platinum-sensitive ovarian cancer (NCT01995188).
  • A phase I/II trial to test demcizumab (OMP-21M18), a monoclonal antibody targeting Delta-like ligand 4 (DLL4), an activator of the Notch signaling pathway (which is known to be important in cancer stem cells and cancer), in patients with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer (NCT01952249).
  • A phase I trial of monalizumab, targeting NKG2A receptors, in patients with ovarian, fallopian tube, and peritoneal cancer (NCT02459301)

Checkpoint Inhibitors and Immune Modulators

Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.

  • Three phase II trials of pembrolizumab (Keytruda®, MK-3475), an anti-PD-1 antibody, in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancer (NCT02608684, NCT02440425, NCT02537444).
  • A phase I/II trial of durvalumab (MEDI4736), an anti-PD-L1 checkpoint inhibitor, in patients with recurrent ovarian cancer (NCT02484404).
  • A phase I/II trial of durvalumab (MEDI4736) and motolimod, a Toll-like receptor 8 agonist, for patients with ovarian, primary peritoneal, or fallopian tube cancer for whom doxorubicin is indicated (NCT02431559). This is sponsored by the Cancer Research Institute.
  • A phase I study of durvalumab (MEDI4736) and tremelimumab, a CTLA-4 checkpoint inhibitor, for patients with advanced solid tumors, including ovarian, primary peritoneal, or fallopian tube cancer (NCT01975831). This is sponsored by the Cancer Research Institute.
  • A phase I/II study to test nivolumab (Opdivo®), a PD-1 antibody, combined with INCB024360, an IDO1 inhibitor, in patients with advanced cancer, including ovarian, fallopian tube, or primary peritoneal cancer (NCT02327078).

Therapeutic Vaccines

Scientists have identified several ovarian cancer-associated antigens—molecules on or in cells that are capable of eliciting an immune response—that can serve as targets for immune recognition and attack. These include several “cancer-testis” antigens, which are expressed only by cancer cells and not by healthy tissues (with the exception of the testis and, occasionally, placenta), making them promising targets for cancer immunotherapy. One of these, NY-ESO-1, is under investigation by researchers in the CRI/Ludwig Clinical Trials Network. Research by CRI investigator Kunle Odunsi, M.D., Ph.D., has shown that NY-ESO-1 expression may be found in up to 43% of ovarian cancers.

Several studies of antigen-based vaccines are currently recruiting patients with ovarian cancer, including:

  • A phase II/III trial of gemogenovatucel-T (Vigil™) for patients with stage 3/4 high-grade ovarian, fallopian tube, and primary peritoneal cancer (NCT02346747).
  • A phase II trial of TroVax® (MVA-5T4), targeting the 5T4 antigen, versus placebo in patients with relapsed asymptomatic ovarian cancer (NCT01556841).
  • A phase II trial of a dendritic cell vaccine for patients with advanced ovarian cancer (NCT00703105).
  • A phase I/II trial combining CDX-1401, which targets the NY-ESO-1 protein, epacadostat (INCB024360), an IDO1 inhibitor, and Poly-ICLC, a Toll-like receptor 3 stimulant, in ovarian, fallopian tube, or primary peritoneal cancer in remission (NCT02166905).
  • A phase I/II study of a dendritic cell vaccine for patients with advanced ovarian, fallopian tube, or peritoneal cancer (NCT02432378).
  • A phase I trial of CMB305 in patients with locally advanced, relapsed, or metastatic cancer that expresses NY-ESO-1, including ovarian cancer (NCT02387125).
  • A phase I study of a p53 vaccine for patients with ovarian, fallopian tube, or peritoneal cancer (NCT02275039).
  • A phase I trial of a vaccine given with Montanide and Poly-ICLC, a Toll-like receptor 3 stimulant, for patients with ovarian, fallopian tube, or peritoneal cancer ( NCT02452775).
  • A phase I trial in metastatic solid tumors, including ovarian cancer, of a vaccine targeting the HER2 antigen (NCT01376505).
  • A phase I trial testing ID-LV305, a vaccine targeting the NY-ESO-1 antigen, in patients with solid tumors, including ovarian cancer (NCT02122861).

Adoptive Cell Transfer

A fourth major avenue of immunotherapy for ovarian cancer is adoptive T cell transfer. In this approach, immune cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several phase I and II trials of adoptive T cell transfer techniques are currently under way for patients with ovarian cancer, including:

  • A phase II trial to test white blood cells genetically engineered to recognize NY-ESO-1 for patients with metastatic cancer (NCT01967823).
  • White blood cells genetically engineered to recognize NY-ESO-1, given along with dendritic cells pulsed with NY-ESO-1 antigen as a vaccine, in a phase II trial for patients with stage IV, advanced, or refractory malignancies (NCT01697527).
  • A phase I/II trial testing T cells genetically engineered to target the MAGE-A3 antigen in patients with ovarian cancer (NCT02111850)
  • A phase I/II study to test chimeric antigen receptor (CAR) T cell therapy targeting mesothelin, which is overexpressed in ovarian cancer, pancreatic cancer, and mesothelioma (NCT01583686).
  • A phase I/II trial to test T cells genetically engineered to target the MAGE-A3 or NY-ESO-1 antigens in patients with ovarian cancer (NCT01567891).

Oncolytic Viruses

Oncolytic virus therapy uses a modified virus that can cause tumor cells to self-destruct and generate a greater immune response against the cancer.

  • A phase II trial testing a measles virus genetically enhanced to express the thyroidal sodium symporter gene (MV-NIS) in patients with ovarian, fallopian tube, or peritoneal cancer (NCT02364713).

Adjuvant Immunotherapies

Adjuvant immunotherapies are substances that are either used alone or combined with other immunotherapies to boost the immune response even more.

  • A phase I study of epacadostat (INCB024360), an IDO1 inhibitor, for patients with ovarian, fallopian tube, or peritoneal cancer (NCT02118285).

Go to our Cancer Immunotherapy Clinical Trial Finder to find clinical trials of immunotherapies for ovarian cancer that are currently enrolling patients.

To read more about ovarian cancer and immunotherapy on CancerResearch.org, click here.

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