HER2 vaccine showed benefits for gastric cancer patients in an early trial
The cancer vaccine HER-Vaxx (IMU-131, Imugene) was well tolerated in 10 evaluable gastric cancer patients who received three doses together with standard-of-care chemotherapy in a Phase 1b study. Five subjects reported partial responses in shrinking tumors by ≥30%, and four subjects showed disease stabilization.
HER-Vaxx is a fusion peptide of three HER2 epitopes designed to stimulate a B-cell response. It was shown in preclinical studies and in a Phase 1 study in breast cancer to elicit polyclonal antibodies against different regions of the HER2 receptor.
Influenza vaccination rates increased in the US
Uptake of the seasonal influenza vaccine in the US reached 45% through mid-November, according to estimates by the Centers for Disease Control and Prevention (CDCP). That represents an increase of >6 percentage points from the previous season. While the numbers may change by the end of the season, the majority of people get their vaccine before the end of November, according to the CDCP.
The 2017/8 influenza season was one of the most severe in recent years, with almost one million hospitalizations and 80,000 deaths in the US alone.
Checkpoint inhibition better than chemotherapy in a late-stage trial
The PD-1 inhibitor pembrolizumab (Keytruda, Merck & Co Inc.) was more effective and less toxic than standard-of-care chemotherapy in treating chemotherapy-resistant head-and-neck cancer.1 The international, randomized, open-label Phase 3 study of 500 patients showed that median survival was 8.4 months for the pembrolizumab cohort and 6.9 months for the chemotherapy group. The median duration of response was 18 and 5 months, and one-year survival was 37% and 27%, respectively.
“It’s fairly clear that patients whose tumors express PD-L1 are most likely to benefit from this type of immunotherapy drug,” lead investigator Ezra Cohen of University of California in San Diego said. “In this trial, overall survival was driven by PD-L1 expression. Only patients whose tumors expressed PD-L1 had a response to pembrolizumab, and those responses tended to be durable.”
1. Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ; KEYNOTE – investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2018; doi: 10.1016/S0140-6736(18)31999-8
First pediatric hexavalent vaccine approved in the US
The US Food and Drug Administration (FDA) has approved the hexavalent vaccine Vaxelis (Sanofi & Merck & Co. Inc.) for children aged six weeks to four years. The vaccine, which protects against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Hemophilus influenzae type b, is administered in three doses. It was approved in the EU in 2016.
Early data show promise for a CAR-T treatment of multiple myeloma
11 patients with high-risk recurrent myeloma, who were evaluated in a preliminary analysis of a Phase 1 trial, benefited from a BCMA-targeting CAR-T therapy. All subjects saw their tumors disappear, with only two relapses within initial 6 months. BCMA is a B-cell maturation antigen overexpressed on malignant plasma cells.
The treatment, which involved infusion of a mixture of genetically engineered cytotoxic and helper T cells, was safe with only mild toxicities.
Experimental Ebola vaccine is used widely in Congo outbreak
The Ebola vaccine rVSV-ZEBOV (Merck & Co. Inc.) has had a major impact in the current outbreak in the Democratic Republic of Congo, according to the World Health Organization. The vaccine – the most advanced one in clinical development – is administered to people who came into contact with infected individuals and to their acquaintances in the so-called ring vaccination. >40,000 people have received the vaccine.
500 Ebola cases have been reported since August 2018 with 285 confirmed deaths as of December, making it the second largest outbreak after the devastating epidemic in West Africa in 2014–6.
Combination immunotherapy against HPV-related cancers is being tested in a Phase 2 trial
An open-label Phase 2 study is enrolling 77 patients with HPV-induced cervical, anal, penile, and vulvar cancers to test a combination of the vaccine MEDI0457 (VGX-3100) and the PD-L1 inhibitor durvalumab (Imfinzi, both MedImmune). MEDI0457 is an IL-12-adjuvanted DNA vaccine targeting HPV strains 16 and 18. It has been tested for treatment of precancerous cervical lesions.
“HPV-associated cancers behave similarly, regardless of site of origin, and should be studied as a whole, not as individual cancers. This study will be ‘site agnostic’, meaning any patient with an HPV 16/18 associated cancer, regardless of primary site, will be eligible,” trial leader Michael Frumovitz of MD Anderson Cancer Center said.
Lyme disease vaccine entered a Phase 2 study
The Lyme disease vaccine candidate VLA15 (Valneva) is being tested in a two-stage Phase 2 trial. The first part will assess safety and select the most immunogenic of three different dosage levels in 120 individuals. In the second part, 450 subjects will be randomized to receive three injections one month apart or placebo. The trial takes place in US and Europe where Lyme disease is endemic.
VLA15 is a subunit vaccine containing the outer surface protein A of Borrelia burgdorferi but lacking the part of the protein which is believed to be responsible for adverse reactions to a previously licensed vaccine, LYMErix (GSK). VLA15, which is the only Lyme disease vaccine in clinical development, showed a good safety profile and induced specific antibody responses in a Phase 1 trial.
Dengvaxia was approved in the EU
The European Commission has approved the dengue vaccine Dengvaxia (Sanofi) for use in people aged 9–45 years with a documented prior infection and who live in dengue-endemic tropical territories. The mosquito-borne disease is a particular health concern in tropical regions threatening half of the world’s population.
Dengvaxia has been approved in several countries of Latin America and Southeast Asia. The Philippines had launched a national campaign before it was determined that the vaccine exacerbates the course of infection in dengue-naïve subjects. The campaign was later stopped.
Chikungunya vaccine candidate fast-tracked in the US
The FDA has granted the fast-track designation for the chikungunya vaccine VLA1553 (Valneva). The monovalent, single-dose, live-attenuated vaccine is in Phase 1 testing. It was shown to be safe and highly immunogenic in preclinical studies. The fast-track designation facilitates development of vaccines for diseases with major unmet clinical needs.
Quebec starts using mixed HPV vaccine regimen in a controversial move
Health officials in Quebec, Canada, have modified the HPV vaccination program to include a first dose of the 9-valent Gardasil-9 (Merck & Co. Inc.) and second dose of the 2-valent Cervarix (GSK). So far students have received two doses of Gardasil-9. The change in policy should save the government $3 million per year.
However, some experts criticize the move in that the new regimen might not induce sufficient immunity against the seven HPV strains not covered by Cervarix, leading to increased vulnerability to genital warts. Moreover, Cervarix is de facto used off-label, since it has not been approved for boys in Canada.