SOME OF MY OBSERVATIONS DURING IMMUNOVATIVE’S PHASE I/II TRIAL IN CARLSBAD, CALIFORNIA

I am a board certified Emergency Physician who participated in Immunovative Therapies Ltd.’s Phase I/II trial in Carlsbad, California.  I was responsible for onsite patient safety and functioned as a co-investigator in this first-in-human clinical trial in which AlloStim® administration was combined with cryoablation of a selected tumor lesion.  The results of this study, along with three-year follow-up data, are currently being prepared for submission to a peer-reviewed journal.  An abstract, entitled “Response of HER2+ breast cancer patients to allogeneic cell immunotherapy” was presented at the 2012 ASCO Annual Meeting and describes the responses of the trial’s breast cancer patients at the one year follow-up

 The study group was comprised of 42 extremely unfortunate, severely debilitated, metastatic cancer patients who were heavily pre-treated and who had chemotherapy-resistant disease.  Their average ECOG score was 2.2 and they averaged 22.2 metastatic lesions.  These patients were mostly referred from hospice settings. We estimated that these patients had an average life expectancy of 60 days.  Many of these patients had large, extremely disfiguring lesions and were in constant, severe pain.  Some were wheelchair-bound due to pathological fractures secondary to progressive bone metastases.  All study patients’ immune systems were compromised by previous surgery, radiation, and chemotherapy.

The tumor debulking I witnessed during this trial was nothing short of remarkable.  All study patients appeared to respond to the AlloStim® infusion protocol.  Also, all patients reported a subjective improvement in well-being after the first few AlloStim® injections.  It is unclear if this was a placebo effect or was due to the fact that the patients were no longer on toxic chemotherapy drugs.  Later we found that those patients with the highest IL-12 levels achieved the most prolonged survival.  Below I describe three of the more dramatic cases that I witnessed:

1 – A 52-year-old female presented with two visible large, fungating lesions breast cancer lesions.  One had recurred at the site of her left breast mastectomy and the other had broken through the skin in the area of her axillary nodes.  These surface lesions gave off a strong odor of rotting flesh.  This patient also had metastatic lesions in her lungs, liver, bones and other multiple lymph nodes.  This patient had volunteered for the trial primarily to try and minimize the odor and disfiguring surface lesions which prevented her grandchildren from wanting to be near her.  She received the three weekly intradermal AlloStim® injections followed by cryoablation of a liver lesion + intravenous AlloStim®.  She later received additional intravenous AlloStim® booster doses.  Tumor regression was easily visible on the surface lesions at 30 days after initiation of treatment, and the lesions were almost completely healed at three months.   Six months after treatment, the skin over the patient’s breast lesions had completely regrown and the strong odor had disappeared.   I felt this was a dramatic example of successful immune debulking of a rapidly progressive, chemotherapy-resistant and inoperable tumor.  This patient went on to live over two years after treatment (photographs of this patient’s progress can be seen by clicking here and scrolling to page 16).

2 – A 68-year-old male presented with very advanced metastatic malignant melanoma.  He had failed all conventional treatment, and his tumor was rapidly progressing.  He had refused chemotherapy, and the melanoma had grown into an extremely large mass, measuring approximately 15 cm x 20 cm x 15 cm, on his anterior right chest.  This mass was comprised entirely of solid tumor with only a small area of central necrosis.  After the first three weekly intradermal AlloStim® injections, cryoablation was performed on this mass and intra-lesional and intravenous AlloStim® boosters were administered.  A second cryoablation and intravenous injection was planned due to the patient’s very large tumor burden.  When cryoablation of the large chest wall mass was attempted the second time, it was noted that the mass had almost entirely liquefied.  I was amazed as over four liters of liquefied contents were removed from the lesion with a suction apparatus!   This huge mass of metastatic melanoma had been almost entirely debulked with immune therapy.  This unfortunate patient had such a massive tumor burden involving such extensive organ spread and bone destruction that he was unable to stand or walk, had to be moved using a specially designed crane, and required complete daily care.  Although this patient ultimately died from pneumonia six months after the experimental treatment, his case further demonstrated to me AlloStim®’s remarkable immune debulking activity against solid tumors.

3 – A 51-year-old female entered the trial with metastatic breast cancer.  She had extensive bone metastases and was confined to a wheelchair a good part of each day.  She had exhausted all conventional treatment options and had a life expectancy of two months or less.  This patient’s PET scan showed extensive involvement of the spine and peripheral skeleton.  After starting the AlloStim®/cryoablation protocol, this patient had markedly decreased pain and increased mobility, eventually improving to the point where she was able to walk normally and even go scuba diving with her family!  A post-treatment PET scan showed a dramatic decrease in the amount of bone and liver involvement.  This patient maintained a markedly improved quality of life until her death over two years after her initial treatment. This patient’s husband wrote extensively about his experiences as he supported his wife during her treatment and guided her through the stresses of experimental therapy. You can read this blog at www.caringbridge.com/visit/marl.

These remarkable cases are only a few of the many positive responses I personally witnessed during the Carlsbad Phase I/II study.   In my opinion, virtually all treated patients, with their wide range of tumor types, achieved some benefit.  One interesting observation was that the radiologic imaging did not show decreasing tumor size, even though the patients seemed to live longer than expected. We hypothesized that the tumors were actually swollen by an immune response and thus only appeared larger.

I spoke regularly with the patients’ referring oncologists.  They were also amazed that the patients continued to improve even though the radiologists regularly reported progressive disease.   Although this was a preliminary non-randomized trial, the survival of these very ill patients was a median of 163 days at the two year follow up, as compared with an expected survival of only about 60 days. The observed tumor debulking, improved quality of life and appearance of increased survival gave us the confidence to advance AlloStim® to Phase IIa/b trials to optimize the protocol dosing and frequency and to select a single indication for Phase II/III testing. 

The patients in this Phase I/II study had immune systems that were already ravaged by chemotherapy, radiation, and massive tumor burdens.  In spite of this, many exhibited dramatic immune tumor debulking.   This raised the questions: How would a less immune compromised patient with a smaller tumor respond to AlloStim®?  If AlloStim® was used earlier in the disease course, could it completely rid the patient of disease?  These are exciting questions that need to be answered as the clinical applications of this unique immunotherapy evolve.

I will continue to collaborate with Immunovative Therapies, Ltd. in future trials here in the United States.

Michael H. Bishop D.O.

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Treatment strategy designed to use the power of the human immune system to kill tumors and prevent their recurrence.
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