The PD-1 inhibitor pembrolizumab advances through clinical development in multiple cancer types
The US FDA has approved the PD-1 inhibitory MAb pembrolizumab (Keytruda, Merck) for treatment of stage IB-IIIa non-small cell lung cancer in adult patients who have undergone surgery and platinum chemotherapy. The immune checkpoint inhibitor (ICI) reduced the risk of death or disease recurrence by 27% compared to placebo in the Phase 3 KEYNOTE-091 trial.
First-line pembrolizumab in combination with chemotherapy improved survival in subjects with advanced or unresectable biliary tract cancer enrolled in the Phase 3 KEYNOTE-966 trial. No specific rates of survival have been disclosed. Biliary tract cancer patients face poor prognosis, with only 5-15% five-year survival.
Another combination of pembrolizumab, with the AI-assisted neoepitope vaccine EVX-01 (Evaxion), received the FDA’s fast-track designation for treatment of metastatic melanoma. The combination had demonstrated an objective response rate of 67% and complete response rate of 22% in an early trial.
Checkpoint inhibitors prove beneficial in late-stage trials
The PD-L1 inhibitor atezolizumab (Tecentriq) together with the VEGF-seocific bevacizumab (Avastin, both Genentech) following surgery significantly improved recurrence-free survival, compared to active surveillance, in patients with early-stage hepatocellular carcinoma participating in the Phase 3 IMbrave050 trial. No specific rates were disclosed.
The combination of two ICIs, anti-CTLA-4 botensilimab and anti-PD-1 balstilimab (both Agenus), induced 23% overall response rate and 63% one-year survival rate in 70 subjects with heavily pretreated microsatellite-stable colorectal cancer enrolled in a Phase 1b trial. The typical rates for this patient population treated by standard of care are 5% and 25%, respectively.
New types of Covid-19 vaccines on the horizon
As the Covid-19 pandemic recedes from public discourse and severe cases continue to dwindle, clinical development of new vaccines continues. The whole virion inactivated vaccine Covaxin (Ocugen) was safe with no adverse events in >400 adults. Both vaccine-naïve individuals and those with prior mRNA vaccination were enrolled in the Phase 2/3 trial. The TLR7/8 agonist-adjuvanted vaccine targets most or all important surface antigens, thus providing a broader immune response than approved vaccines.
The recombinant vaccine DYAI-100 (Dyadic) has entered a dose-escalation Phase 1 trial to be evaluated for safety and immunogenicity as a booster dose in healthy volunteers. The recombinant protein vaccine targets the receptor-binding domain of SARS-CoV-2.
24-valent PCV receives breakthrough designation
The FDA has granted breakthrough designation to the 24-valent pneumococcal conjugate vaccine VAX-24 (Vaxcyte). The decision is based on Phase 1/2 trial data showing non-inferiority of VAX-24 to the licensed 20-valent Prevnar 20 in terms of safety and immunogenicity to the shared strains.
Alzheimer’s disease vaccine shows promise in early trial
The amyloid-beta vaccine ACI-24.060 (AC Immune) was safe and elicited antibody responses after two weeks in patients with prodromal stage Alzheimer’s disease. Interim results of the Phase 1/2 ABATE trial analyzed lower dose of the vaccine; a higher-dose cohort has just begun the trial.
ACI-24.060, administered in two doses four weeks apart, is designed to induce polyclonal antibodies protective against the pathological oligomeric and pyroglutamate forms of amyloid-beta, thus inhibiting plaque formation and disease progression.