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In a phase 3 trial, participants with early Alzheimer’s disease who received the monoclonal antibody lecanemab had less decline on measures of cognition and function at 18 months than those who received placebo.

Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC. In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy. Randomisation was done using an interactive response technology system and was stratified by investigator's choice of radiotherapy regimen, tumour site and p16 status, and disease stage, with participants randomly assigned in blocks of four per stratum. Participants, investigators, and sponsor personnel were masked to treatment assignments. Local pharmacists were aware of assignments to support treatment preparation. Pembrolizumab and placebo were administered intravenously once every 3 weeks for up to 17 doses (one before chemoradiotherapy, two during chemoradiotherapy, 14 as maintenance therapy). Chemoradiotherapy included cisplatin (100 mg/m2) administered intravenously once every 3 weeks for two or three doses and accelerated or standard fractionation radiotherapy (70 Gy delivered in 35 fractions). The primary endpoint was event-free survival analysed in all randomly assigned participants. Safety was analysed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03040999, and is active but not recruiting. Between April 19, 2017, and May 2, 2019, 804 participants were randomly assigned to the pembrolizumab group (n=402) or the placebo group (n=402). 660 (82%) of 804 participants were male, 144 (18%) were female, and 622 (77%) were White. Median study follow-up was 47·7 months (IQR 42·1–52·3). Median event-free survival was not reached (95% CI 44·7 months–not reached) in the pembrolizumab group and 46·6 months (27·5–not reached) in the placebo group (hazard ratio 0·83 [95% CI 0·68–1·03]; log-rank p=0·043 [significance threshold, p≤0·024]). 367 (92%) of 398 participants treated in the pembrolizumab group and 352 (88%) of 398 participants treated in the placebo group had grade 3 or worse adverse events. The most common grade 3 or worse adverse events were decreased neutrophil count (108 [27%] of 398 participants in the pembrolizumab group vs 100 [25%] of 398 participants in the placebo group), stomatitis (80 [20%] vs 69 [17%]), anaemia (80 [20%] vs 61 [15%]), dysphagia (76 [19%] vs 62 [16%]), and decreased lymphocyte count (76 [19%] vs 81 [20%]). Serious adverse events occurred in 245 (62%) participants in the pembrolizumab group versus 197 (49%) participants in the placebo group, most commonly pneumonia (43 [11%] vs 25 [6%]), acute kidney injury (33 [8%] vs 30 [8%]), and febrile neutropenia (24 [6%] vs seven [2%]). Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group (one participant each from aspiration pneumonia, end-stage renal disease, pneumonia, and sclerosing cholangitis) and six (2%) participants in the placebo group (three participants from pharyngeal haemorrhage and one participant each from mouth haemorrhage, post-procedural haemorrhage, and sepsis). Pembrolizumab plus chemoradiotherapy did not significantly improve event-free survival compared with chemoradiotherapy alone in a molecularly unselected, locally advanced HNSCC population. No new safety signals were seen. Locally advanced HNSCC remains a challenging disease that requires better treatment approaches. Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65–79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10 −5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10 −5 were reported in 35 patients (26%, 95% confidence interval (CI) 19–34) in IsaRd versus 71 (53%, 95% CI 44–61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89–5.28, P  < 0.0001). The MRD benefit was consistent across subgroups at 10 −5 and 10 −6 , and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P  < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P  = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10 −5 , the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 . In patients with newly diagnosed, transplant-ineligible multiple myeloma, addition of weekly bortzomib to isatuximab, lenalidomide and dexamethasone leads to increased minimal residual disease negativity compared with isatuximab, lenalidomide and dexamethasone.

Lenvatinib plus either pembrolizumab or everolimus was compared with sunitinib as first-line therapy for advanced renal cell cancer. Progression-free survival was significantly longer with lenvatinib plus pembrolizumab than with sunitinib. Lenvatinib plus everolimus was also more effective than sunitinib, but the difference was smaller.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Benralizumab, a monoclonal antibody against the interleukin-5α receptor expressed on eosinophils, may be an option for treating EGPA. We conducted a multicenter, double-blind, phase 3, randomized, active-controlled noninferiority trial to evaluate the efficacy and safety of benralizumab as compared with mepolizumab. Adults with relapsing or refractory EGPA who were receiving standard care were randomly assigned in a 1:1 ratio to receive benralizumab (30 mg) or mepolizumab (300 mg) subcutaneously every 4 weeks for 52 weeks. The primary end point was remission at weeks 36 and 48 (prespecified noninferiority margin, -25 percentage points). Secondary end points included the accrued duration of remission, time to first relapse, oral glucocorticoid use, eosinophil count, and safety. A total of 140 patients underwent randomization (70 assigned to each group). The adjusted percentage of patients with remission at weeks 36 and 48 was 59% in the benralizumab group and 56% in the mepolizumab group (difference, 3 percentage points; 95% confidence interval [CI], -13 to 18; P = 0.73 for superiority), showing noninferiority but not superiority of benralizumab to mepolizumab. The accrued duration of remission and the time to first relapse were similar in the two groups. Complete withdrawal of oral glucocorticoids during weeks 48 through 52 was achieved in 41% of the patients who received benralizumab and 26% of those who received mepolizumab. The mean (±SD) blood eosinophil count at baseline was 306.0±225.0 per microliter in the benralizumab group and 384.9±563.6 per microliter in the mepolizumab group, decreasing to 32.4±40.8 and 71.8±54.4 per microliter, respectively, at week 52. Adverse events were reported in 90% of the patients in the benralizumab group and 96% of those in the mepolizumab group; serious adverse events were reported in 6% and 13%, respectively. Benralizumab was noninferior to mepolizumab for the induction of remission in patients with relapsing or refractory EGPA. (Funded by AstraZeneca; MANDARA ClinicalTrials.gov number, NCT04157348.).

In this ongoing, randomized, phase 3 trial, sotrovimab (a SARS-CoV-2–targeted monoclonal antibody) or placebo was administered to outpatients within 5 days after the onset of Covid-19 symptoms. The incidence of hospitalization for any cause or death was lower among patients who received sotrovimab (1% vs. 7%).

In a trial comparing enfortumab vedotin and a PD-1 inhibitor with chemotherapy in patients with untreated advanced or metastatic urothelial cancer, progression-free and overall survival nearly doubled with the experimental treatment.

Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. In this clinical trial, a single dose of nirsevimab resulted in a significantly lower incidence of medically attended RSV-associated lower respiratory tract infection than that with placebo.

This phase 3, placebo-controlled platform trial evaluated a single infusion of casirivimab and imdevimab (REGEN-COV) at 2400-mg and 1200-mg doses in outpatients with acute SARS-CoV-2 infection. The incidence of Covid-19–related hospitalization was lower and recovery was faster among patients who received the antibody combination than among those who received placebo.

Emicizumab binds to activated factor IX and factor X, reproducing the bridging function of the missing factor VIII. In a trial of emicizumab prophylaxis, emicizumab every 1 or 2 weeks led to a lower bleeding rate than no prophylaxis.