Therapeutic HPV vaccine improves survival of cancer patients treated with ICI
The HPV vaccine PDS0101 (PDS Biotech) combined with recombinant IL-12 and the immune checkpoint inhibitor (ICI) pembrolizumab (Keytruda, Merck) induced a three-year survival rate of 75% in 8 ICI-naïve patients with advanced HPV16-positive cancers. The typical survival rate in this population is < 30% after two years.
The Phase 2 trial also reported a 70% survival rate at the 1-year mark in subjects who had failed a prior line of ICI immunotherapy.
The first chikungunya vaccine has been approved
The US Food and Drug Administration (FDA) has approved the chikungunya vaccine VLA 1553 (Ixchiq, Valneva) for adults at high risk of exposure to the virus. The decision, which is conditional on performing Phase 4 surveillance studies, follows large-scale safety trials in which 3,500 individuals received the vaccine.
VLA1553 is a single-dose, live attenuated vaccine against the mosquito-borne viral infection, which is a significant public health burden in tropical regions of the world.
PD-1 pathway inhibitors help patients with more cancer indications
The FDA has approved the PD-1-targeting MAb pembrolizumab combined with chemotherapy as first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma. The approval is based on the Phase 3 KEYNOTE-859 trial, which showed survival extended by 12%, compared to chemotherapy alone, and manageable toxicity.Citation1
The PD-L1 inhibitor durvalumab (Imfinzi, AstraZeneca), administered together with the angiogenesis inhibitor bevacizumab, extended progression-free survival in hepatocellular carcinoma (HCC) patients eligible for embolization. No actual survival numbers from the Phase 3 EMERALD-1 trial have been announced. HCC affects almost one million people a year, of whom 20–30% are eligible for embolization.
PCV-21 was safe and immunogenic for all vaccine serotype strains in a phase 3 trial
The 21-valent pneumococcal conjugate vaccine (PCV) V116 (Merck) elicited immune responses to all targeted serotypes, including non-inferior responses to those shared with the licensed PCV-20. The randomized, double-blind Phase 3 STRIDE-3 trial, which enrolled > 2,600 PCV-naïve adults, also reported safety profile comparable to licensed PCVs.
The pneumococcal strains targeted by V116 account for > 80% of invasive disease cases in older adults. The vaccine is administered in a single dose.
Food allergy immunotherapy in clinical development
The epicutaneous peanut allergy immunotherapy Viaskin Peanut (DBV Technologies) induced tolerance to ≥ 1,000 mg of peanut protein after two years in 81% of toddlers aged 1–3 years enrolled in the Phase 3 EPITOPE trial. No treatment-related serious adverse events have been observed.
The oral multi-food allergy immunotherapy ADP101 (Alladapt Immunotherapeutics) was granted FDA’s Fast-Track designation. The treatment showed safety and dose-dependent efficacy in desensitization to one of 15 food allergens in children aged 4–17 years involved in the Phase 1/2 Harmony trial.
All-time high rate of childhood vaccine exemptions in US
The US Centers for Disease Control and Prevention reported the highest-ever rate of vaccine exemptions in kindergarten children due to religious or other personal beliefs of their parents.Citation2 While the overall vaccine coverage remained the same compared to last year (~93% for all vaccines in the study), exemptions increased by 0.4% points to 3%.
Exemption rate exceeded 5% in 10 US states, and overall variation ranged from < 1% in West Virginia to 12% in Idaho.
Only 11–13 states had >95% coverage of the main pediatric vaccines, which is considered a threshold for herd immunity and reliable prevention of outbreaks.
Gamma-delta T cell therapy increased survival in glioblastoma
The gamma-delta T cell-based immunotherapy IN8bio (IN8bio) extended progression-free survival in all newly diagnosed glioblastoma patients beyond 7 months typically seen with standard of care. Two subjects enrolled in the Phase 1 trial remained alive after two years, and no treatment-related serious adverse events were observed.
INB-200 consists of autologous gamma-delta T cells genetically engineered to be resistant to chemotherapy, which is administered concomitantly.
SARS-CoV-2 vaccine produced in fungus cells succeeds in a safety trial
The filamentous fungus-produced COVID-19 vaccine DYAI-100 (Dyadic) was safe and immunogenic in 30 healthy adults involved in a double-blind, placebo-controlled, dose-escalation Phase 1 trial.
The vaccine, which is tested as a booster dose, consists of Alhydrogel-adjuvanted recombinant receptor-binding domain of the spike protein from SARS-CoV-2 produced in the fungus Thermothelomyces heterothallica.
CAR-T cell therapy might lead to secondary cancers
The FDA investigates reports of T-cell cancers following treatment with BCMA- and CD19-directed CAR-T cell therapies. CAR-positive lymphoma has been observed in subjects receiving various marketed and investigational products. The agency considers regulatory measures while stating that the overall benefits of the treatment still outweigh potential risks.
CAR-T cell therapy consists of autologous T cells engineered to recognize a cancer-specific antigens. Only CAR-T cells recognizing CD19 and BCMA have been approved so far.
References
- Rha SY, Oh DY, Yañez P, Bai Y, Ryu MH, Lee J, Rivera F, Alves GV, Garrido M, Shiu KK, et al. KEYNOTE-859 investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24(11):1181–2. doi:10.1016/S1470-2045(23)00515-6.
- Seither R, Yusuf OB, Dramann D, Calhoun K, Mugerwa-Kasujja A, Knighton CL. Coverage with selected vaccines and exemption from school vaccine requirements among children in kindergarten - United States, 2022-23 school year. MMWR Morb Mortal Wkly Rep. 2023;72(45):1217–1224. doi:10.15585/mmwr.mm7245a2.