ADXS-HPV immunotherapy promising for anal cancer
Preliminary data from a Phase 1/2 trial indicate that Advaxis' immunotherapy ADXS-HPV is effective in patients with HPV-associated locally advanced anal cancer. All ten patients who finished treatment showed a complete response and no evidence of recurrence. Follow-ups ranged from 0.5 to 24 months, while the primary objective is to monitor response after 6 months. Among reported side effects were rigors, fever and nausea.
The full study, conducted at Brown University, enrolled 25 patients who received ADXS-HPV in combination with standard chemotherapy and radiation therapy. The Immunotherapy is based on an engineered Listeria monocytogenes strain that, in preclinical studies, was able to generate T-cell responses as well as inhibit regulatory T cells.
“ADXS-HPV has the potential to be an important advancement in the treatment of HPV-associated anal cancer, and we look forward to reporting the full safety and efficacy data set once all 25 patients have completed the dosing regimen,” said Kimberly Perez of Brown University in a press release.
Anal cancers are relatively rare, and most of the cases are linked to HPV infection. Women with a history of cervical cancer have an increased risk of anal cancer.
Physicians face increasing pressure to delay child vaccinations
Some parents want to spread out the recommended vaccine schedule for their children, and many pediatricians succumb to the pressure, according to a study published in Pediatrics1. In a given month, >90% of physicians, who responded to an email survey, encountered a request to delay vaccination in a child <2 years old. More than a fifth reported that >10% of parents made such a request.
A majority of providers said they sometimes agree to spreading out the schedule, even though they think it puts children at higher risk of getting a disease. “Many physicians reported tension between the need to build trust with families by being willing to compromise on the schedule while simultaneously feeling they were putting children at risk and causing them unnecessary pain by spreading out vaccines on multiple visits,” Allison Kempe of University of Colorado School of Medicine said in a statement.1Kempe A, O'Leary ST, Kennedy A, Crane LA, Allison MA, Beaty BL, Hurley LP, Brtnikova M, Jimenez-Zambrano A, Stokley S. Physician Response to Parental Requests to Spread Out the Recommended Vaccine Schedule. Pediatrics 2015; doi: 10.1542/peds.2014–3474
FDA approved Nivolumab for lung cancer treatment
The U.S. Food and Drug Administration has approved nivolumab (BMS, Opdivo) for patients with progressed non-small cell lung cancer (NSCLC). Nivolumab was reviewed in a priority program for drugs with potential for significant improvement of serious conditions, and the decision came 3 months ahead of the expected date. It is approved for patients whose disease progressed after the conventional platinum-based chemotherapy.
Nivolumab had been approved for advanced melanoma, and BMS recently presented strong results showing extended survival in NSCLC patients. It is a PD-1 inhibitor, which prevents tumors from inhibiting the immune response via the PD-1 pathway.
“This approval will provide patients and health care providers with knowledge of the survival advantage associated with Opdivo and will help guide patient care and future lung cancer trials,” FDA's Richard Pazdur said in a press release.
Lung cancer is the leading cause of cancer death accounting for >150,000 deaths annually in the US alone. NSCLC is the most common form of the disease.
Prevenar 13 approved for adults in Europe
The European Medicines Agency approved Pfizer's pneumococcal vaccine Prevenar 13 for use in adults. The decision came after the CAPiTA trial showed that Prevenar, which contains antigens for 13 pneumococcal strains, is able to decrease the incidence of community-acquired pneumonia in adults >65 years by almost 50%.
“This is particularly important for older adults and those with medical conditions that may make them more vulnerable to this serious, debilitating and potentially deadly disease,” Pfizer's Rene Reinert said in a statement.
Prevenar 13 is the world's best-selling vaccine, and Pfizer is facing some criticism for its high price. Earlier this year, the company lowered the cost in some developed countries from $3.30 to $3.10 per dose, but according to the medical CRO Médecins Sans Frontières, the vaccine should best become available in the developing world for $5 per 3 doses.
Combination immunotherapy successful in preclinical study against melanoma
The combination of BRAF inhibitor dabrafenib, MEK inhibitor trametinib, and immunotherapy (antigen-specific adoptive cell transfer or anti-PD1 antibody) looks promising in treatment of metastatic melanoma. In a preclinical setting, the mixture showed a superior anti-tumor effect and complete tumor regression, according to a study published in Science Translational Medicine2.
“The 2 2-drug combination of BRAF and MEK inhibitors works synergistically and decreases the side effects of the BRAF inhibitor on normal cells. We reasoned that this combo would allows us to synergize with immunotherapy without increasing toxicities,” Antoni Ribas of University of California, Los Angeles, said in a press release.
Researchers have begun 2 clinical trials to test safety and efficacy of the combination. According to WHO, >130,000 cases of melanoma occur globally each year and the rate is increasing.2Hu-Lieskovan S, Mok S, Homet Moreno B, Tsoi J, Robert L, Goedert L, Pinheiro EM, Koya RC, Graeber TG, Comin-Anduix B, Ribas A. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAFV600E melanoma. Sci Transl Med 2015; doi: 10.1126/scitranslmed.aaa4691
Promoting HPV vaccination among boys might be cost-effective
Allocating resources to increased HPV vaccination of boys could be more cost-effective than trying to further increase coverage in young females, according to a modeling study published in Epidemics3. Although HPV infection is most commonly associated with cervical cancer, males also are at risk. According to Centers for Disease Control, ˜1/3 of HPV-related cancers occur in men, with head and neck cancers rising in incidence.
Vaccination rates are stagnating, at least in the US, with only 37% of girls and 14% of boys receiving all 3 recommended doses. “The gender with the lowest coverage is the low-hanging fruit,” Marc Ryser of Duke University said in a statement. “Stagnating vaccination rates, coupled with parental opposition, suggest that it could cost less to raise coverage in boys from, say, 14 to 15% than to raise coverage in girls from 37 to 38%.” Making the right trade-off might be beneficial to the entire population.3Ryser MD, McGoff K, Herzog DP, Sivakoff DJ, Myers ER. Impact of coverage-dependent marginal costs on optimal HPV vaccination strategies. Epidemics 2015; 11:32–47
Type 1 diabetes vaccine candidate enters phase 2 trial
The Swedish company Diamyd Medical has initiated a Phase 2 trial of its type 1 diabetes (T1D) vaccine. 80 children, in whom the autoimmune process leading to T1D has already started, will be given Diamyd or placebo and monitored for 5 years.
Diamyd on its own failed a Phase 3 trial. In this trial, it is administered with vitamin D, which should strengthen the vaccine's efficacy.
T1D is an autoimmune disease in which the patient's insulin-producing β cells are attacked. If clinical symptoms develop, the patient must be treated daily with insulin in order to survive.
ACIP recommended Meningitis B vaccination for high-risk groups
The US. Centers for Disease Control's Advisory Committee on Immunization Practices (ACIP) has recommended 2 Meningitis B vaccines for use in high-risk populations, i.e., immunodeficient individuals and people in proximity of ongoing outbreaks.
The Food and Drug Administration has approved the 2 vaccines, Pfizer's Trumenba and Novartis' Bexsero, for the age group 10–25 in the past. The companies would like ACIP's recommendation to be as broad. Unlike other drugs, vaccines often need ACIP's agreement before physicians routinely use them.
Phase 2 trial initiated for pancreatic cancer vaccine plus immunotherapy
Aduro Biotech has begun Phase 2 trial of a vaccine combination targeted at metastatic pancreatic cancer. It contains a mixture of GVAX and CRS-207 vaccines and it is administered with the PD-1 inhibitor nivolumab (BMS, Opdivo), or alone in a control group. This trial, which takes place at 5 US sites, will enroll 88 patients who had one prior chemotherapy.
GVAX and CRS-207 are being investigated in another Phase 2 trial, in which patients receive the combination, CRS-207 only, or standard chemotherapy. The FDA granted the 2 vaccines ‘Breakthrough Therapy’ designations last year.
GVAX is a vaccine derived from a genetically modified human cancer cell line expressing the cytokine granulocyte-macrophage colony-stimulating factor for activating T-cell immunity. CRS-207 is an engineered strain of Listeria monocytogenes that induces potent innate and adaptive immune responses by overexpressing the tumor-associated antigen mesothelin.
England wants to fight rise in Meningitis with a vaccination program
England will offer Meningococcal conjugate vaccine to all teens aged 14–18. According to the health officials, it is a response to the rise of this deadly disease with 117 cases last year compared to 22 in 2009. The program will offer a combination vaccine from GSK protecting against meningitis A, C, W and Y.
“We are working with NHS England, Public Health England and the vaccine manufacturer to develop a plan to tackle the rising number of MenW cases,” John Watson, England's deputy chief medical officer, told The Telegraph.
Two immunotherapeutics combined in clinical trial with renal cell carcinoma
Celldex has teamed up with Roche to enter a Phase 1/2 study of a combination of their 2 immunotherapeutics, varlilumab and MPDL3280A. They will be investigated for safety, tolerability and efficacy against renal cell carcinoma. Varlilumab has shown promising effects in a previous dose-escalation trial involving patients with advanced, refractory tumors.
Varlilumab is a human monoclonal antibody targeting CD27, which is highly exprssed in some cancers, thereby inducing potent antitumor T-cell response. MPDL3280A belongs to a class of PD-1 inhibitors that block the PD-1 pathway in the T-cells, which is hijacked by some tumors to shut down immune response. The combination of the 2 drugs thus have the potential to boost the patient's immune system to fight the tumor.