Same vaccine as Lani posted? If not, is anyone getting this?

[hutchibk]

(Reuters) - Galena Biopharma said its breast cancer vaccine received a patent granting it exclusivity until 2028.

The vaccine, NeuVax, gives immunity against the relapse of breast cancer in patients who have low-to-intermediate levels of HER2 ~ a protein that can affect the growth of cancer cells.

NeuVax is being tested in a late-stage study under a special protocol assessment agreement with the U.S. Food and Drug Administration.

['lizbeth]

Galena Biopharma provides E75 (Neuvax) which is the first generation vaccine. This is being used in a clinical trial for lower expressors of Her2 that do not qualify for Herceptin. My clinical trial nurse, Karen Escamilla, is helping to obtain more enrollment. If you know of anyone who is a lower expressor of Her2 please direct them to the clinical trial information on the internet, put them in touch with Karen at Brooke Army Medical Center, or contact me and I'll pass along the contact information.

Antigen Express provides the second generation vaccine, AE37 - which Dr. Peoples is overseeing the the Walter Reed vaccine trial. This is the vaccine that SandraGA is receiving in her arm of "our" vaccine trial. Anna4969 and I are participating in this trial in the GP2 arm.

In our trial the difference is based on HLA-A2+ or HLA-A2-, a human leukocyte antigen. I'm positive, hence the GP2. Sandra is negative and in the AE37.

I'm very enthusiastic about these vaccine clinical trials, along with TDM1, pertuzumab - and anything else that mobilizes that immune system to conquer our cancer. I'm very unhappy about any treatment that uses chemotherapy that wipes out healthy cells along with cancer cells.

Again, if you know of any ladies who are lower expressors of Her2 (maybe in your support groups or going through treatment at the same time) please encourage them to consider a NeuVax clinical trial.

[anna4969]

I absolutely agree with Lizbeth to encourage any low expressors to enroll or at least investigate the neuvax. It has has wonderful results thus far. My doctor is the principal investigator for this trial and she is brilliant. If I was a low expressor, I would travel from here to the moon to get the neuvax that is how strongly I feel about it. These vaccine are so safe with minimal side effects.

[hutchibk]

1. Are these trials for stage IV?
2. Does it cross the BBB?
3. If you have had Herceptin, do you qualify?

['lizbeth]

Breast cancer vaccine shows survival benefit in subset of low HER2 expressors


By CAROLINE HELWICK | May 1, 2008






SAN DIEGO—Adjuvant treatment with a HER2/neu E75 peptide vaccine significantly reduced mortality in a subset of women with breast cancer, according to a multi-institutional study led by investigators at Brooke Army Medical Center, San Antonio. The study, reported at the 2008 American Association of Cancer Research annual meeting (abstract 2545), showed a survival benefit in women who were “low expressors” of the HER2 protein (particularly IHC 1+ patients).

Linda C. Benavides, MD, a general surgery resident at Brooke Army Medical Center, reported the results. The project’s director is George Peoples, MD, director of the Cancer Vaccine Development Program and chief of surgical oncology at Brooke Army Medical Center.

E75 is a peptide sequence from the HER2/neu protein. E75 stimulates peptide-specific cytotoxic T lymphocytes, which recognize and lyse HER2 cells. It is being developed by Apthera, Scottsdale, Arizona, as NeuVax (see Figure).



The Cancer Vaccine Development Program has conducted clinical trials with the E75 vaccine in node-positive and node-negative patients with varying levels of HER2 expression. In this study, investigators wanted to determine whether the level of HER2 expression affected the response to the vaccine.

The study included 163 patients with early-stage breast cancer (node positive or high-risk node negative) who were categorized according to their level of HER2 expression. Over-expression was defined as FISH ≥ 2.0 or IHC 3+, while low-expression was defined as IHC 1+, IHC 2+, or FISH < 2.0. After HLA typing, patients who were HLA-A2+/A3+ received the novel vaccine intradermally while those who were HLA-A2-/A3- served as controls.

Results were available for 85 patients in the vaccination group (29 over-expressors and 56 low-expressors) and for 66 patients in the control group (22 over-expressors and 44 low-expressors). (Several antigen-naïve, ie, IHC 0, additional patients were included in some of the analyses.)

HER2 over-expressors were similar to the low-expressors regarding prognostic and treatment factors, except that a significantly larger number of vaccinated over-expressors had hormone-receptor-negative tumors. Clinicopathologic factors were not significantly different between controls and vaccinated low-expressors.

Some interesting results

Following vaccination, immunologic responses were similar between over-expressors and low-expressors, as measured by delayed-type hypersensitivity reactions.

“The E75 vaccine was capable of inducing an immune response in all IHC categories,” Dr. Benavides said. Patients who were IHC 1+ demonstrated the greatest immunological response.


At a median follow-up of 30 months, disease recurred at a similar rate among vaccinated HER2 over-expressors and unvaccinated over-expressing controls. Recurrence rates were 18.2% and 13.8%, respectively. However, vaccinated over-expressors who had a recurrence had a 50% lower mortality rate than control patients with recurrence (25% vs 50%), although the difference did not reach statistical significance, Dr. Benavides reported.

Most interesting, she said, was that recurrences were substantially reduced for vaccinated patients with low HER2 expression. Vaccinated low-expressors had a recurrence rate of 10.7%, compared with 18.2% for unvaccinated low-expressors. Importantly, no deaths occurred among the vaccinated low-expressors, while the mortality rate was 38% among the unvaccinated low-expressors (P = .08).

IHC 1+ patients had the greatest reduction in relapses and the most significant reduction in mortality: The mortality rate was 0% for vaccinated IHC 1+ patients vs 20% for IHC 1+ controls (P = .04).

“All vaccinated patients benefited clinically. The vaccinated low-expressors and the IHC 1+ group had the greatest reduction in mortality risk,” Dr. Benavides said. “The exciting thing is that more than 50% of breast cancer patients are low-expressors.”

A theory

The investigators have a theory as to why HER2 low-expressors benefit more than over-expressors.

“We think it has to do with the mechanisms of action of the vaccine and the sensitization or tolerance of the tumor cells,” Dr. Benavides said.

She said that the vaccine stimulates the cytotoxic T-cells to kill any tumor cell expressing any amount of HER2.

“If the immune system has seen a lot of something—in this case an over-expression of HER2—it will not react as robustly,” she said. “It will be sensitized. The vaccine does work in the HER2 over-expressors, but less potently. This is different than trastuzumab(Drug information on trastuzumab) [Herceptin]. Our vaccine is more applicable to the whole spectrum of HER2.”

Phase III trials

The E75 vaccine will be evaluated in two randomized phase III trials. The study in HER2 low-expressors is expected to begin within 6 months and will enroll 700 women at 80 sites worldwide. The second will enroll over-expressors who have completed trastuzumab. The vaccine will also be studied for safety in combination with trastuzumab in over-expressors.

['lizbeth]

Hutchibk,

Here is one that starts "July 2012" for low expressors. These vaccine trials have focused more on primary and early breast cancer. This treatment uses E75 and Herceptin.

http://clinicaltrials.gov/ct2/show/N...rceptin&rank=1

Criteria
Inclusion Criteria:

• Patients will be included in the study based on the following criteria:
  
  • Women 18 years or older
  • Node-positive breast cancer (AJCC N1, N2, or N3)
  • Node-negative breast cancer if negative for both estrogen (ER) and progesterone (PR) receptors and has received chemotherapy as standard of care
  • Clinically cancer-free (no evidence of disease) after standard of care therapy (surgery, chemotherapy, radiation therapy as directed by NCCN guidelines). Hormonal therapy will continue per standard of care. Neoadjuvant chemotherapy is allowed.
  • HER2 expression of 1+ or 2+ by IHC. FISH testing must be performed on IHC 2+ tumors and shown to be non-amplified (≤2.0).
  • HLA-A2 and/or HLA-A3 positive
  • LVEF >50%
  • ECOG 0,1
  • Signed informed consent
  • Adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms)

Exclusion Criteria:

• Patients will be excluded from the study based on the following criteria
  
  • Node-negative breast cancer (AJCC N0 or N0(i+)) unless negative for both estrogen (ER) and progesterone (PR) receptors and has received chemotherapy as standard of care
  • Clinical or radiographic evidence of distant or residual breast cancer
  • HER2 negative (IHC 0) or HER2 3+ or FISH amplified (FISH >2.0)
  • Non-HLA-A2/3 positivity
  • History of prior Herceptin therapy
  • NYHA stage 3 or 4 cardiac disease
  • LVEF <50%
  • Immune deficiency disease or HIV, HBV, HCV
  • Receiving immunosuppressive therapy including chemotherapy, chronic steroids, methotrexate, or other known immunosuppressive agents
  • ECOG ≥2
  • Tbili >1.8, creatinine>2, hemoglobin<10, platelets<50,000, WBC<2,000
  • Pregnancy (assessed by urine HCG)
  • Breast feeding
  • History of autoimmune disease
  • Active pulmonary disease requiring medication to include multiple inhalers
  • Involved in other experimental protocols (except with permission of the other study PI)

[hutchibk]

I guess a call to BAMC is in order... because the original article states "NeuVax is being tested in a late-stage study under a special protocol assessment agreement with the U.S. Food and Drug Administration."

And these Qs will be asked:
1. Are any trials for stage IV/Late stage? Where are they located?
2. Does it cross the BBB?
3. If you have had Herceptin, do you qualify?

['lizbeth]

For the GP2/AE37 trial we started within 6 months after finishing Herceptin or treatment. I messaged Karen about stage IV and BBB.

['lizbeth]

Vaccine Therapy in Treating Patients With Stage IV Breast Cancer

This study is currently recruiting participants.
Verified January 2012 by Fred Hutchinson Cancer Research Center


This phase I/II trial is studying the side effects and best dose of adoptive T cell therapy in treating patients with stage IV breast cancer. Vaccines are given to patient prior the expansion of a person's white blood cells may help the body build an effective immune response to kill tumor cells that overexpress human epidermal growth factor receptor 2 (HER2)

http://www.clinicaltrials.gov/ct2/show/NCT00791037

[hutchibk]

Thank you!! I guess I don't meet protocol if I ever needed it because my platelets hover around 65,000. And I can't afford travel to Seattle, I don't think... but who knows.

Also, even though lapatinib is protocol expected as late stage/heavily pretreated, still no answer to the BBB question for the vaccine...

['lizbeth]

Hutchbik,

I don't know about the BBB, I wonder if it is too early to tell. Also the data might be skewed in the phase II as there were a couple that they suspected might have had undiagnosed brain mets before enrollment. The larger phase III data will improved the picture of what the vaccines can accomplish.

I'm on board with you, it can't be soon enough before we have targeted therapies, or vaccines, or something other than WBR or laser or surgery for brain mets.