The Phase 3 Study of the Prostate Cancer Vaccine Prostvac Has Been Discontinued

An independent Data Monitoring Committee (DMC) recommended that the Phase 3 PROSPECT study of Prostvac in men with metastatic hormone-resistant prostate cancer (mCRPC) should be discontinued due to inadequate results. Prostvac did not improve overall survival. The PROSPECT trial (NCT01322490) was a randomized, double-blind, and placebo-controlled Phase 3 trial that included 1,298 mCRPC patients from 200 sites in 15 countries. These men had minimal or no  symptoms associated with their mCRPC. The trial evaluated whether Prostvac, alone or in combination with granulocyte macrophage colony-stimulating factor (GM-CSF), could improve overall survival compared to a placebo. GM-CSF is a cytokine or signaling molecule that can also stimulate the immune system. It stimulates the production of granulocytes and monocytes, two types of cells in the immune system that are important for fighting infections.

Previous studies evaluating more than 2,000 participants suggested that Prostvac immunotherapy was well-tolerated. In a Phase 2 trial, this immunotherapy showed potential in prolonging survival in men with advanced prostate cancer. However, the interim analysis for the Phase 3 PROSPECT trial suggested that Prostvac may not be as effective as hoped. It is hoped that combination therapies including Prostvac may be more effective. Copenhagen, Denmark-based Bavarian Nordic’s hopes of salvaging Prostvac now rest on whether it can boost the effect of other immuno-oncology agents, notably Bristol-Myers’ PD-1 and CTLA-4 checkpoint inhibitors Opdivo and Yervoy. Publicly, Bavarian Nordic has not given up hope that the cancer vaccine can complement these drugs. For further details, see the Sept. 15th FierceBiotech article and Sept. 21st Prostate Cancer News Today.

Prostvac had been in late stage Phase III development (PROSPECT trial) for metastatic, hormone-resistant prostate cancer patients who are either asymptomatic or minimally symptomatic. It is a therapeutic pox virus cancer vaccine directed at PSA-producing cells. It is administered with or without GM-CSF (granulocyte macrophage colony-stimulating factor, a protein secreted by immune system cells that functions as a white blood cell growth factor. Prostvac immunotherapy (administered by s.c. injections) is intended to trigger a specific and targeted immune response against prostate cancer cells and tissue by using virus-based immunotherapies that carry the tumor-associated antigen PSA (prostate-specific antigen) along with 3 natural human immune-enhancing costimulatory molecules collectively designated as TRICOM (LFA-3, ICAM-1, and B7.1 When PSA-TRICOM is presented to the immune system in Prostvac, cytotoxic T lymphocytes (CTLs) are generated that may recognize and kill PSA-expressing cancer cells.

This website has been covering Prostvac development for several years. See blogs posted August 5th, 2014 and May 15th, 2017 among others.

Prostate Cancer Symptoms May Not Always Be Obvious

An article from Fox Chase Cancer Center in Philadelphia published Sept. 21st in the U.S. National Library of Medicine MedlinePlus described a list prostate cancer symptoms. Prostate cancer symptoms may be confused with signs of other common but noncancerous disorders, such as benign prostatic hyperplasia. Symptoms of prostate cancer may include: trouble starting to urinate; weak or interrupted flow of urine; urinating more often, particularly during the night; trouble emptying the bladder; pain or burning during urination; bloody urine or semen; painful ejaculation; and/or chronic pain in the back, hips or pelvis. Although about 1 in 7 men will be eventually be diagnosed with prostate cancer in his lifetime, the warning signs of the disease are often vague and may be confused with other conditions.

Prostate cancer is rare in men younger than 40 years old but once they reach 50, the risk increases. Nearly 6 out of 10 men with prostate cancer are older than 65 years old, the Fox Chase specialists said. Black men are more likely than men of other races and ethnicities to be diagnosed with prostate cancer and die from the disease. Black men are also more likely to develop advanced disease and have the condition at a younger age.

Genetics may also play a role in why some men develop prostate cancer. Men whose father or brother have the disease are more than twice as likely to also be diagnosed. The risk increases if several family members are affected and if these men were diagnosed at a younger age. Men who are 55 and older should discuss their risk factors for prostate cancer with their doctor and determine if screening is right for them.

Additional Studies of Opdivo (nivolumab) in Combination with Rubraca in Prostate Cancer and Other Applications of Opdivo.

Editorial note: I am writing some of this post while awaiting Hurricane Irma to pass my home directly in about 1-2 hours.

Opdivo® (nivolumab) and the prostate cancer vaccine Prostvac are being combined in a National Cancer Institute clinical trial described in posts on this website dated May 15th and August 7th, 2017. Bristol Myers Squibb and Clovis Technology will collaborate to assess the combination of Opdivo® (nivolumab) and the PARP inhibitor, Rubraca (rucaparib) in Phase 2 and 3 clinical studies in patients with different cancer types, including prostate cancer.

The companies plan to launch a Phase 2 study to investigate the safety and effectiveness of the combination treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). All studies are expected to begin before the end of 2017.

“We are very enthusiastic about studying Rubraca and Opdivo® in combination, and the potential to create new treatment options for patients with multiple tumor types, as well as for patients beyond those with BRCA mutations,” according to Patrick J. Mahaffy, Clovis Oncology’s president and CEO. “This substantial clinical collaboration in ovarian, triple-negative breast and prostate cancers represents a significant effort by Clovis and Bristol-Myers Squibb to realize that potential,” he said.

Cancer cells are constantly multiplying, but the division process is sometimes associated with errors that may cause their death, such as DNA breaks. If cancer cells repair these breaks, they survive and keep multiplying.

Rubraca is an oral inhibitor of PARP proteins (PARP-1, PARP-2, and PARP-3), which are involved in DNA repair. By inhibiting these proteins, Rubraca prevents cancer cells to repair their DNA. Indeed, previous studies have shown that PARP inhibition promotes inflammation, cell death, and increases the action of T-cells within tumors.

Opdivo® acts upon a protein called programmed cell death-1 (PD-1), which inhibits the immune system’s ability to detect cancer cells. By inhibiting PD-1, Opdivo® restores the body’s capacity to activate the anti-tumor response and fight cancer cells. Because of its potential role as an enhancer of the immune system’s response, Opdivo® is under evaluation in a broad range of clinical trials across all phases in a variety of tumor types. For more information, see the following.

Additional results involving Opdivo® include an article published September 11th in MedlinePlus describing research suggesting that Opdivo® — a drug that works with the immune system to fight melanoma — is more effective than the current standard of care for patients who’ve had surgery to remove advanced tumors. In addition, an August 17th post from the National Cancer Institute Current Contents stated that the Food and Drug Administration has approved Opdivo® for patients with metastatic colorectal cancer that has one of two specific genetic features and whose disease has progressed after chemotherapy.

Everything You Need to Know About the PSA Test from the National Cancer Institute

The National Cancer Institute (NCI, the largest of the institutes of the National Institutes of Health, NIH) recently published an excellent fact sheet describing many aspects related to prostate-specific antigen (PSA) testing. Specific subjects addressed include: a) what is the PSA test? b) Is the PSA test recommended for prostate cancer screening? c) What is a normal PSA result? d) What if screening shows an elevated level? e) Limitations and potential harms of using the PSA test for prostate cancer screening; f) Recent research on prostate cancer screening; g) How is the PSA test used in men who have been treated for prostate cancer? h) What does a PSA increase mean for men who have been treated? i) How are researchers trying to improve the PSA test?

Osteoporosis Therapies Like Prolia Improve Bone Health in Prostate Cancer Patients

Decreasing bone mineral density (BMD) is also an undesirable side effect of androgen deprivation (hormonal) therapy (ADT). The therapy is associated with many potential adverse effects, including significant bone loss and increased risk for low trauma or fragility fractures similar to that in persons with primary osteoporosis. A recent review of clinical trial results revealed that patients with non-metastatic prostate cancer receiving ADT can benefit from osteoporosis therapies, known as bisphosphonates e.g. (Fosamax, Boniva), and from Prolia (denosumab), which significantly increase bone mineral density (BMD). The review, entitled “Bone Health and Bone-Targeted Therapies for Nonmetastatic Prostate Cancer” was recently published in the journal Annals of Internal Medicine.

 The new study by researchers at the University of Toronto found that non-metastatic prostate cancer patients starting or continuing ADT had significantly less BMD loss when they were given bisphosphonates (a class of medicines that slow down or prevent bone loss) and Prolia (the only FDA-approved therapy for cancer treatment-induced bone loss), compared with those receiving a placebo, normal care, or other active treatments.

The review set out to evaluate the effectiveness of drug, supplement, and lifestyle interventions currently employed as measures to prevent fractures, improve BMD, and delay osteoporosis in non-metastatic prostate cancer patients. Bisphosphonates were found to increase BMD over a placebo, but had no effect at preventing fractures among patients with non-metastatic prostate cancer. Prolia, administered subcutaneously every six months in a 60 mg concentration, improved BMD and reduced the incidence of new vertebral fractures, according to the results of one clinical trial.

According to Dr. David Samadi, MD, chairman of urology at New York’s Lenox Hill Hospital, “this study should remind all urologists of the gap in regards to bone health care for men with prostate cancer. More testing of bone mineral density both before and during ADT treatment is an important step in identifying those men who may be at risk. One beginning step is to do a risk assessment tool evaluating men with prostate cancer receiving ADT and educating them on the adverse effects of ADT. We also need to be mindful of talking to our patients about their diet and lifestyle making sure they are getting adequate sources of calcium and exercising regularly,” Samadi said.