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Small Phase I Study Reports 2 to 4 Year Ovarian Cancer Remission in 30% of Women Who Received a NY-ESO-1 Vaccine

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Three of nine patients (33%) remain in complete clinical remission at 25, 38, and 52 months, respectively.

The cancer-testis antigen NY-ESO-1 is expressed in greater than 40% of advanced epithelial ovarian cancers and represents a promising immunotherapeutic target. In a small Phase I (safety and immunogenicity) clinical trial conducted by Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, nine “high-risk” epithelial ovarian cancer patients, who were in first clinical remission after primary surgery and chemotherapy, received NY-ESO-1b peptide and Montanide ISA-51 every 3 weeks in the form of five vaccinations. The “high risk” ovarian cancer patient criterion was defined as a patient who (i) received suboptimal primary debulking (remaining tumor masses with diameter of 1.0 cm or greater), or (ii) experienced a failure to normalize the CA 125 blood tumor marker by the end of the third cycle of first-line chemotherapy. In addition, each patient enrolled in the trial was required to test positive for (i) human leukocyte antigen 2A (HLA-2A) in the blood, and (ii) NY-ESO-1 or LAGE-1 tumor expression. NY-ESO-1 tumor expression was evaluated for each patient by immunohistochemistry (IHC). LAGE-1 tumor expression was evaluated for each patient by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis. For each patient, NY-ESO-1 specific humoral immunity (ELISA), T-cell immunity (tetramer and ELISPOT), and delayed-type hypersensitivity were assessed pre-vaccination and at week #1, week #4, week #7, week #10, week #13, and week #16 of the vaccination period.

The nine patients experienced treatment-related adverse events including: grade 1 fatigue, anemia, pruritus, myalgias, and hyperthyroidism; and grade 2 hypothyroidism. There were no grade 3/grade 4 adverse events. The results of the Phase I trial are set forth below.

  • Three of four patients (75%) with NY-ESO-1-positive tumor showed T-cell immunity.
  • Four of five patients (80%) with NY-ESO-1-negative tumor showed T-cell immunity.
  • At median follow-up of 11.3 months, six of nine patients (67%) have recurred, with a median progression-free survival (PFS) of 13 months.
  • Three of nine patients (33%) remain in complete clinical remission at 25, 38, and 52 months, respectively.

At the end of the Phase I trial, the trial investigators concluded that vaccination of high-risk, HLA-A2-positive epithelial ovarian cancer patients with NY-ESO-1b and Montanide has minimal toxicity and induces specific T-cell immunity in patients with both NY-ESO-1-positive and NY-ESO-1-negative tumors. Also, the trial investigators noted that additional study is necessary. For a copy of the clinical trial protocol associated with this trial, click here.

[Source: “Safety and Immunogenicity Study of NY-ESO-1b Peptide and Montanide ISA-51 Vaccination of Patients with Epithelial Ovarian Cancer in High-Risk First Remission;” Diefenbach, C.S. et. al.; Clin Cancer Res. 2008 May 1;14(9):2740-2748.]

Comment: Prior cancer vaccines targeting NY-ESO-1 overexpression in ovarian cancer tumors produced moderate success in terms of an increase in PFS. This study is particularly provocative because patients who tested positive and negative for NY-ESO-1 tumor expression experienced T-cell immunity, and “high risk” patients (including suboptimally debulked patients) experienced PFS benefit.

Related Information:

Avax Technologies Announces Initiation of Clinical Study With Autologous Ovarian Cancer Vaccine

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“AVAX Technologies, Inc. (OTC Market:AVXT.OB) today announces it has received FDA approval to begin enrollment into a Phase I-II clinical trial of OVax® for patients with advanced, chemotherapy-refractive ovarian cancer. [For a copy of the clinical trial inclusion/exclusion criteria refer to “OVax®: A Feasibility Study Using a DNP-Modified Autologous Ovarian Tumor Cell Vaccine as Therapy in Ovarian Cancer Patients After Relapse.”]. The study will be performed in collaboration with Cancer Treatment Centers of America, Inc (CTCA). It will be centered in the CTCA hospital in Zion, Illinois, although patients also will be referred from other CTCA hospitals in Tulsa and Philadelphia, and its out-patient clinic in Seattle.

Up to 42 eligible patients with stage III or IV ovarian carcinoma will be enrolled. These patients’ cancers will have progressed despite initial surgery and chemotherapy and failed to respond to one or two salvage chemotherapy regimens. They will undergo debulking surgery, and tumor tissue will be sent to AVAX for production of vaccine. Post-operatively, they will receive intraperitoneal chemotherapy with a taxane and then will be enrolled into the protocol.

Three doses of OVax will be tested, and each of the three doses will be analyzed for immunological efficacy with the goal of optimizing the dose for treatment of patients in future trials.

‘We are enthusiastic about receiving FDA clearance to start this important clinical trial and with the opportunity it affords us to collaborate with CTCA,’ stated Dr. David Berd, Chief Medical Officer of AVAX. ‘Clearly, better treatments for ovarian cancer are needed and we hope that OVax will eventually find its place as a relatively non-toxic therapeutic alternative for these patients. This alliance with CTCA will allow us to expand the therapeutic utility of the AC Vaccine platform along with our ongoing Phase I/II program in non-small cell lung cancer and our recently launched Phase III pivotal registration study in melanoma (MVALDI).’

As part of the business collaboration CTCA has made an up-front payment of $250,000 and will begin to make monthly payments of $25,000 upon the initiation of production of vaccines at AVAX’s Philadelphia manufacturing facility.

‘We are very excited to be part of a new chapter in the fight against ovarian cancer,’ said Dr. Edgar Staren, Chief Medical Officer at Cancer Treatment Centers of America. ‘Ovarian cancer is a very complex cancer that is often resistant to chemotherapy, radiation and surgery. At Cancer Treatment Centers of America, our commitment to cancer patients is to help fight their cancer with the most advanced medical technology available. This partnership with AVAX gives hope to ovarian cancer patients who are told far too often that there is nothing more that can be done for them. This treatment option will work well with our unique integrative care model that combines state-of-the-art traditional medicine with scientifically-based complementary therapies such as aggressive nutritional management and support, naturopathic medicine, physical therapy, mind-body medicine and spiritual support to go beyond treating the tumor and supporting the needs of the whole person – all under one roof.’

About the AC Vaccine Therapeutic

The AC Vaccine is an immunotherapy prepared by attaching a small chemical to the patient’s tumor cells in a process known as haptenization. This hapten modification allows the tumor cells to stimulate a T cell-based immune response to a patients own tumor cells. An early indicator of T cell immune activity is Delayed Type Hypersensitivity (DTH).

An understanding of what AVAX calls the immunopharmacology of the AC Vaccines is critical to their effective use. AVAX believes that the optimal dose, schedule of administration, and route of administration of human cancer vaccines must be established before they enter advanced phase studies, and that some competing vaccine technologies have failed because their developers ignored one or more of these parameters in early phase development. The optimum schedule and best route of administration (intradermal) to be used for OVax were determined by extensive phase I-II studies of MVax. The latest phase I-II trial was completed last year and the results will be presented at the 2008 [Annual] meeting of the American Society of Clinical Oncology (ASCO).”

[Quoted Source: “AVAX Technologies Announces Initiation of Clinical Study with Autologous Ovarian Cancer Vaccine (OVax®),” BusinessWire news release dated April 9, 2008.]

Comment: The OVax®vaccine clinical trial carries great promise. The trial will combine three potent approaches to battling ovarian cancer: (i) debulking surgery, (ii) intraperitoneal chemotherapy with a taxane drug, and (iii) a custom made vaccine created from the ovarian cancer survivor’s own tumor. Please watch the video below regarding the OVax® vaccine for ovarian cancer.

Five Years Later, Patient Participating in Vaccine Trial Remains Free of Ovarian Cancer

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“Like most women with ovarian cancer, 44-year-old Christine Sable of Lancaster, Pennsylvania, did not discover she had the disease until it was in the advanced stages and had spread to other areas of the abdomen. ‘I knew my chances of recurrence were very high-75 to 80 percent at that particular stage-and that the disease would likely recur within a year or two,’she says. ‘Once it recurs, it is difficult to cure.’

After aggressive surgery and chemotherapy, the only other option her doctor could offer was more chemotherapy. But the first round had been ‘very hard,’ Sable recalls. ‘I wanted to find something that would work with my own immune system and not be so harsh on my body.’

Then she learned about a Phase I clinical research study of an ovarian cancer vaccine developed by Kunle Odunsi, MD, PhD, Surgeon in Gynecologic Oncology and Co-Leader of the Tumor Immunology and Immunotherapy Program at Roswell Park [Cancer Institute]. The vaccine is designed to trigger an immune response in the significant number of women who have tumors that test positive for the antigen NY-ESO-1.

The study was open to patients who had completed their initial treatments and who had no further evidence of disease; Sable fit the profile. She says the day she was accepted into the study was ‘one of the most exciting days of my life.’ She began treatment at Roswell Park in February 2004, and her immune system responded so strongly to the first five doses of vaccine that she received another five, then another five, each time experiencing a better response-with no side effects. Now 49 and still cancer-free, she returns to Roswell Park just once a year for continued monitoring.

Odunsi is currently leading a team of Roswell Park researchers who are working to improve the vaccine’s effectiveness. The vaccine is an important new focus in the search for better treatments for ovarian cancer, which is often difficult to treat. Sable says participating in the trial ‘was a very good experience; I was very well cared for. Dr. Odunsi is a gentle, kind man, brilliant and dedicated and very compassionate.’ In May of 2008, Sable will mark the fifth anniversary of her diagnosis and survival. ‘To have had this many years cancer-free is really amazing.’

The study in which she participated was supported by the Cancer Vaccine Collaborative Program of the Cancer Research Institute and Ludwig Institute for Cancer Research, and results were reported in the … [NY-ESO-1 Peptide Vaccine Phase I Clinical Trial Results, Odunsi, K et. al., Proceedings of the National Academy of Sciences, Vol. 141, no 31, July 31, 2007].” [Quoted Source: Science Daily News Release dated April 7, 2008.]

In March 2008, The Ovarian Cancer Research Fund (OCRF) awarded a $900,000 research grant to Dr. Odunsi and his colleagues at the Roswell Park Cancer Institute (RPCI) to fund a collaborative study with the stated goal of developing a promising vaccine to unleash the power of the immune system against cancer. The prestigious award will allow Dr. Odunsi and the RPCI research team to combine four different immunotherapy approaches, all designed to enhance the immune system’s response to ovarian cancer. [Source: “Roswell Park Cancer Institute awarded three-years funding for ovarian cancer vaccine,” a News-Medical.Net News Release dated April 7, 2008.]

Comment: Vaccine or immunotherapy can play an important role in an ovarian cancer survivor’s overarching treatment strategy. This aspect of treatment is often overlooked. It is important to be aware of the availability of vaccine therapy as early as possible in treatment because most clinical trials utilizing vaccine therapy require an extremely low disease “tumor burden” or no (macroscopic) evidence of disease as a prerequisite for patient eligibility. Low tumor burden or no evidence of disease is generally present immediately after chemotherapy treatment(s) resulting in “complete remission,” and/or surgery resulting in “optimal debulking/cytoreduction.” Christine Sable is an excellent example of an ovarian cancer survivor who is proactively managing her care through enrollment in a beneficial clinical trial.

The Roswell Park Cancer Institute, as of this writing, is currently recruiting Stage II through IV ovarian cancer participants for a Phase II vaccine clinical trial involving the use of “Recombinant Vaccinia-NY-ESO-1 (rF-NY-ESO-1) and Recombinant Fowlpox-NY-ESO-1 (rF-NY-ESO-1) in Patients With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen.” For more information with respect to this clinical trial, contact the Roswell Park Cancer Institute Clinical Trials Office at 877-275-7724.

I encourage you to watch the video segment below which addresses Christine Sable’s case, including an interview with Kunle Odunsi, M.D., Ph.D.., the Co-Leader of the Tumor Immunology and Immunotherapy Program at Roswell Park.

MediaSourceTV Video Segment Re

Christine Sable and Roswell Park Cancer Institute Clinical Trial Vaccine Program