Touzeau C, Mina R, Quach H
… +46 more, Hungria V, Bhutani D, Chen W, Kumar S, Chaulagain C, Dimopoulos MA, Bahlis NJ, Maral S, van de Donk NWCJ, Schmidt Filho J, Saja K, Teipel R, Ando M, Roeloffzen W, Annibali O, Augustson B, Botta C, Delforge M, Bourgeois E, Buda G, Hus M, Perrot A, Preis M, Beksac M, Pour L, Farmer S, Nunes M, Oriol A, Melchardt T, Hu Y, Flogegård M, Wang D, Pei L, Wroblewski S, Ariës IM, Quijano Cardé NA, Perova T, de Jager T, Yeh TM, Vanquickelberghe V, Shah P, Chastain K, Kobos R, Carson R, Landgren O, MajesTEC-9 Trial Investigators
N Engl J Med
· 2026 May · PMID 42212933
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BACKGROUND: The efficacy of teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, as early-line monotherapy in relapsed or refractory multiple myeloma is unclear. METHODS: We randomly assigned p...BACKGROUND: The efficacy of teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, as early-line monotherapy in relapsed or refractory multiple myeloma is unclear. METHODS: We randomly assigned patients with relapsed or refractory multiple myeloma who had previously received one, two, or three lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, to receive teclistamab or the investigator's choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). Antimicrobial prophylaxis and immune globulin replacement were recommended. The primary end point was progression-free survival as assessed by an independent review committee. RESULTS: A total of 296 patients were assigned to teclistamab and 297 to PVd or Kd. At the interim analysis (median follow-up, 17.3 months), teclistamab significantly improved progression-free survival as compared with PVd or Kd (estimated 18-month progression-free survival, 69.8% vs. 26.9%; hazard ratio for disease progression or death, 0.29; 95% confidence interval [CI], 0.23 to 0.38; P<0.001). The percentage of patients with a complete response or better was higher with teclistamab than with PVd or Kd (65.9% vs. 16.8%, P<0.001). Overall survival was improved with teclistamab as compared with PVd or Kd (estimated 18-month overall survival, 79.2% vs. 68.6%; hazard ratio for death, 0.60; 95% CI, 0.43 to 0.83; P = 0.002). Adverse events of grade 3 or 4 occurred in 84.9% of teclistamab recipients and in 76.3% of PVd or Kd recipients, with grade 5 adverse events in 6.5% and 3.5%, respectively. Cytokine release syndrome, mostly of grade 1 or 2, occurred in 66.0% of teclistamab recipients, and immune effector cell-associated neurotoxicity syndrome occurred in 4.1%. Grade 3 or 4 infection occurred in 41.6% of teclistamab recipients and in 29.0% of PVd or Kd recipients. CONCLUSIONS: Among patients with multiple myeloma and one to three previous lines of therapy, teclistamab significantly improved progression-free and overall survival as compared with PVd or Kd. Infections of grade 3 or 4 were common. (Funded by Johnson & Johnson; MajesTEC-9 ClinicalTrials.gov number, NCT05572515.).
Zhou C, Greillier L, Liu G
… +28 more, John T, Xing L, Kowalski D, Memmott RM, Yazici O, Sun M, Shu C, Pons-Tostivint E, Fan Y, Fernandez-Hinojal G, Shum E, Wang M, Bertolini F, Camidge DR, Zhou C, Doucet L, Hong Q, Fang J, Huang D, Jin B, Yu Y, Antonuzzo L, Moro-Sibilot D, Bennouna J, de Castro G, Zheng L, Heymach JV, WU-KONG28 Investigators
N Engl J Med
· 2026 May · PMID 42212913
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BACKGROUND: Sunvozertinib received accelerated approval for use in later lines of therapy for patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion mutations...BACKGROUND: Sunvozertinib received accelerated approval for use in later lines of therapy for patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion mutations. Data are needed on the efficacy and safety of sunvozertinib as a first-line treatment for NSCLC. METHODS: In this phase 3, international trial, we randomly assigned, in a 1:1 ratio, patients with advanced nonsquamous NSCLC with exon 20 insertions to receive sunvozertinib or chemotherapy (carboplatin-pemetrexed). The primary end point was progression-free survival as assessed by blinded independent central review. Crossover to the sunvozertinib group was allowed after disease progression was confirmed. Secondary end points included overall survival, investigator-assessed progression-free survival, objective response (complete or partial response), change in tumor size, and duration of response. RESULTS: A total of 324 patients were randomly assigned to receive sunvozertinib (163 patients) or chemotherapy (161 patients). Treatment with sunvozertinib led to significantly longer median progression-free survival than chemotherapy (10.3 vs. 7.5 months; hazard ratio for disease progression or death, 0.65; 95% confidence interval, 0.50 to 0.85; P<0.001). At 12 months, progression-free survival was reported in 46.1% of the patients in the sunvozertinib group and in 26.7% of those in the chemotherapy group; the data for overall survival were immature (38.9% maturity). The percentage of patients with an objective response was 58.9% in the sunvozertinib group and 31.1% in the chemotherapy group; the median best percentage change in tumor size was -42.1% and -24.7% respectively, and the median duration of response was 11.2 and 7.1 months. Grade 3 or higher adverse events were reported in 75.5% of the patients in the sunvozertinib group and in 56.7% of those in the chemotherapy group. In the sunvozertinib group, the most common adverse events of grade 3 or higher included increased serum creatine kinase levels, diarrhea, and anemia. No deaths were attributed to adverse events considered by the investigators to be related to sunvozertinib. CONCLUSIONS: The efficacy of sunvozertinib was superior to that of chemotherapy as first-line treatment for advanced NSCLC with exon 20 insertions. (Funded by Dizal Pharmaceuticals; WU-KONG28 ClinicalTrials.gov number, NCT05668988.).
Hou J, Lim SG, Buti M
… +46 more, Yuen MF, Gane E, Lampertico P, Terrault N, Nguyen H, Yim HJ, Xie Q, Lin J, Qiu Y, Jeng WJ, Heo J, Peng CY, Chen CH, Chuang WL, Xie Y, Hlebowicz M, Idriz N, Mehta R, Agarwal K, Gomes da Silva MM, Franca A, Cernat R, Leerapun A, Coffin CS, Gadano A, Andreone P, Fujiyama S, Sevastianos V, Suzuki Y, Ratziu V, Riachi G, Stocker H, Lim TH, Asselah T, Tanaka Y, Holmes J, Liang X, Cremer J, Lukić T, Plein H, Quinn G, Tao Y, Paff M, Theodore D, Elston R, B-Well Study Group
N Engl J Med
· 2026 Jun · PMID 42206582
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BACKGROUND: Treatment with bepirovirsen, an antisense oligonucleotide targeting hepatitis B virus (HBV) transcripts, has the potential to result in a functional cure, defined by at least 24 weeks of a sustained HBV DNA l...BACKGROUND: Treatment with bepirovirsen, an antisense oligonucleotide targeting hepatitis B virus (HBV) transcripts, has the potential to result in a functional cure, defined by at least 24 weeks of a sustained HBV DNA level below the lower limit of quantification (LLOQ) and hepatitis B surface antigen (HBsAg) loss after fixed-duration therapy. METHODS: In two replicate, double-blind trials (B-Well 1 and B-Well 2), we randomly assigned adults with noncirrhotic chronic HBV infection in a 2:1 ratio to receive subcutaneous bepirovirsen (at a weekly dose of 300 mg) or placebo for 24 weeks. All the patients were receiving stable nucleoside or nucleotide analogue (NA) therapy and had an HBsAg level of more than 100 to 3000 IU per milliliter. Eligible patients discontinued NA therapy at 48 weeks. The primary outcome was a functional cure at week 72. RESULTS: The percentage of patients with a functional cure at week 72 was significantly higher with bepirovirsen than with placebo both in the B-Well 1 trial (in 127 of 650 patients [20%] vs. none of 328 patients) and in the B-Well 2 trial (in 106 of 570 patients [19%] vs. none of 286 patients). In a pooled analysis at 72 weeks, adverse events were reported in 91% of the patients in the bepirovirsen groups and in 73% of those in the placebo groups; serious adverse events were reported in 7% and 4% of the patients, respectively. During the treatment period, adverse events of grade 3 or higher were reported in 16% of the patients who received bepirovirsen and in 3% of those who received placebo; increases in the alanine aminotransferase level were the most common grade 3 adverse events with bepirovirsen (in 6% of the patients). CONCLUSIONS: In two phase 3 trials involving patients with chronic HBV infection, a functional cure after the discontinuation of NA therapy was reported in significantly more patients treated with bepirovirsen than in those who received placebo. (Funded by GSK; ClinicalTrials.gov numbers, NCT05630807 and NCT05630820.).
Gonzalez CE, Fletcher A, Jenkins TL
… +25 more, Zahraeifard S, Peterson R, Taylor M, Jones C, Urban A, Avila D, Campillay M, Wilhelm J, Soldatos A, Kuhle J, Jain P, Corey S, Bergerson JRE, Reich DS, Highfill S, Stroncek D, Dinh A, Pittaluga S, Kong HH, Su HC, Notarangelo LD, Pai SY, Grimley M, Freeman AF, Cortese I
N Engl J Med
· 2026 May · PMID 42202329
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Ware RE, Opoka RO, Latham T
… +11 more, Kasirye P, Kasembo P, Hume H, Birungi I, Kadde N, Wambaka B, Nakafeero M, Conroy AL, Tomlinson G, Lane A, John C
N Engl J Med
· 2026 May · PMID 42202328
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