Immunotherapeutics targeting the PD-1 pathway mark clinical progress in multiple cancer types
The PD-1 inhibitor MAb pembrolizumab (Keytruda, Merck) extended event-free survival and increased response rate, compared to neoadjuvant chemotherapy and placebo, in almost 800 patients with resectable stage 2-3B non-small cell lung cancer (NSCLC). Pembrolizumab was administered both before and after surgery in the randomized, double-blind Phase 3 KEYNOTE-671 trial tested.
Pembrolizumab in combination with chemotherapy also extended overall survival in unresectable, advanced or metastatic malignant pleural mesothelioma, compared to chemotherapy alone. The randomized, open-label KEYNOTE-483 Phase 2/3 trial enrolled >400 subjects.
The PD-L1 inhibitory MAb durvalumab (Imfinzi, AstraZeneca) combined with chemotherapy and surgery improved event-free survival, compared to chemotherapy and surgery alone, in 800 early-stage NSCLC patients involved in the randomized, double-blind, placebo-controlled Phase 3 AEGEAN trial.
No specific numbers have been disclosed for the above trials.
Pembrolizumab and another PD-1 inhibitor MAb dostarlimab (Jemperli, GSK) reduced the risk of tumor progression or death by ~70% in mismatch repair-deficient, advanced endometrial cancer. The two different Phase 3 trials investigated long-term effects at the 1- and 2-year marks, respectively.
Finally, a third PD-1 inhibitor MAb, retifanlimab (Zynyz, Incyte), has been approved by the US Food and Drug Administration (FDA) for treatment of metastatic or recurrent locally advanced Merkel cell carcinoma, based on the POD1UM–201 trial showing that the immune checkpoint inhibitor induced >50% response rate with 18% complete response rate.
FDA’s advisory panel recommends two RSV vaccines
The FDA’s advisory committee has recommended the approval of the RSVpreF (Abrysvo, Pfizer) and RSVPreF3 (GSK) vaccines for prevention of respiratory syncytial virus infection in older adults. In Phase 3 trials, the vaccines were 67% and 83% effective, respectively.
The only concern was that rare cases of Guillain–Barré syndrome were reported from the trials, but the committee decided that the benefits of vaccination outweigh potential risks.
There is no approved vaccine for RSV, which is a serious threat for young children and the elderly.
Therapeutic vaccine shows immunogenicity against HPV
The therapeutic HPV vaccine VTP-200 (Vaccitech) was safe and immunogenic in 58 women with low-grade cervical lesions, according to interim data of the Phase 1/2 HPV001 trial. VTP-200, a hexavalent vaccine targeting five HPV serotypes, is administered as a ChAdOx-vectored prime and MVA-vectored boost.
No therapeutic HPV vaccine is available to the almost 300 million women with persistent HPV infection, the major cause of cervical, oropharyngeal, and other cancers.
WHO revises COVID-19 vaccine guidelines
The World Health Organization (WHO) revised recommendations on COVID-19 vaccinations. While older adults and people with comorbidities should continue to be vaccinated 6–12 months after the latest dose, healthy children and adolescents are considered low-priority.
As the COVID-19 pandemic lost momentum thanks to widespread vaccination and the rise of the Omicron variant, other factors, such as cost-effectiveness, should be taken into account, according to the WHO.
Combination meningococcal vaccine regimen is safe and immunogenic
The combined pentavalent meningococcal vaccine MenABCWY (GSK) was well tolerated and elicited non-inferior immune responses to all five Neisseria meningitidis strains, compared to those induced by each component vaccine separately. The Phase 3 trial involves >3,600 subjects aged 10–25.
MenABCWY, which is administered in two doses 6 months apart, consists of the meningococcal B-targeting Bexsero and the ACWY strain-targeting Menveo (both GSK). These five serotypes cause the vast majority of invasive meningococcal disease cases.
Maternal vaccination against HIV and Zika was immunogenic in a preclinical trial
Two nanoparticle, self-amplifying replicon mRNA vaccines for HIV and Zika (HDT Bio) induced virus-specific antibodies in pregnant rabbits and their kits.Citation1 An additional dose after birth or 4 weeks later maintained high antibody levels in the newborn animals.
A high dose of the self-replicating vaccines, which increase antigen expression up to 100-fold compared to non-replicating mRNA vaccines, was well tolerated with no observable effect on litter size.
Reference
- Khandhar AP, Landon CD, Archer J, Krieger K, Warner NL, Randall S, Berube BJ, Erasmus JH, Sather DN, Staats HF. Evaluation of repRNA vaccine for induction and in utero transfer of maternal antibodies in a pregnant rabbit model. Mol Ther. 2023;31(4):1046–2. S1525-0016(23)00120-X. doi:10.1016/j.ymthe.2023.02.022.