BTK Inhibitor for Chronic Immune Thrombocytopenia: On September 2, 2025, the U.S. Food and Drug Administration (FDA) approved the Bruton’s tyrosine kinase (BTK) inhibitor rilzabrutinib (Wayrilz) tablets to treat adults with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to immunoglobulins, anti-D therapy, or corticosteroids.
The safety and efficacy of rilzabrutinib were evaluated in a 24-week, double-blind, parallel-group study. In this study, 202 patients were randomly assigned to receive either rilzabrutinib (n = 133) or placebo (n = 69). During the 24-week treatment period, 31 patients (23%) given rilzabrutinib and no patients given placebo achieved a sufficient and durable platelet count response (ie, an increased number of platelets from baseline lasting the majority of the last 12 weeks of the treatment period), as determined by the study. The most common side effects were diarrhea, nausea, headache, abdominal pain, and COVID-19 infection. The recommended dosage is 400 mg taken orally twice daily.
Kinase Inhibitors Approved in NSCLC: On August 8, the FDA granted accelerated approval to zongertinib (Hernexeos), a kinase inhibitor, for adults with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD)–activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy. The FDA also approved the Oncomine Dx Target Test as a companion diagnostic device.
Efficacy was evaluated in Beamion LUNG-1, an open-label, multicenter, multicohort trial. Among 71 patients who received prior platinum-based chemotherapy but had not been previously treated with a HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugate, the objective response rate was 75% (95% CI = 63%–83%), with 58% having a duration of response lasting at least 6 months. Among 34 patients previously treated with platinum-based chemotherapy and an HER2-targeted antibody-drug conjugate, the objective response rate was 44% (95% CI = 29%–61%), with 27% having a duration of response lasting at least 6 months.
The prescribing information for zongertinib includes warnings and precautions for hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis, and embryofetal toxicity. The recommended zongertinib dose is based on body weight. For patients weighing < 90 kg, the dose is 120 mg orally once daily; for patients weighing ≥ 90 kg, the dose is 180 mg orally once daily.
On July 2, the FDA granted accelerated approval to sunvozertinib (Zegfrovy), a selective EGFR tyrosine kinase inhibitor, for adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. The FDA also approved the Oncomine Dx Express Test as a companion diagnostic device.
Efficacy was evaluated in WU-KONG1, a multinational, open-label, dose randomization trial. Eligible patients had locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations with disease progression on or after platinum-based chemotherapy. The primary efficacy population included 85 patients who received 200 mg of sunvozertinib orally once daily with food until disease progression or intolerable toxicity. The overall response rate was 46% (95% confidence interval [CI] = 35%–57%), and the duration of response was 11.1 months (95% CI = 8.2 months to not evaluable).
The sunvozertinib prescribing information includes warnings and precautions for interstitial lung disease/pneumonitis, gastrointestinal adverse reactions, dermatologic adverse reactions, ocular toxicity, and embryofetal toxicity. The recommended dose of sunvozertinib is 200 mg orally once daily with food until disease progression or unacceptable toxicity.
Protease Activator for Diffuse Midline Glioma: On August 6, the FDA granted accelerated approval to dordaviprone (Modeyso), a protease activator, for patients aged 1 year and older with diffuse midline glioma harboring an H3 K27M mutation who have progressive disease after prior therapy. This represents the first FDA approval of a systemic therapy for H3 K27M–mutant diffuse midline glioma.
Efficacy was evaluated in an integrated efficacy population of 50 adult and pediatric patients with recurrent H3 K27M–mutant diffuse midline glioma enrolled across five open-label, nonrandomized clinical trials conducted in the United States (ONC006, ONC013, ONC014, ONC016, and ONC018). The efficacy population comprised patients who received single-agent dordaviprone. Patients with diffuse intrinsic pontine glioma, primary spinal tumors, atypical histologies, or cerebrospinal fluid dissemination were excluded.
The overall response rate was 22% (95% CI = 12%–36%), and the median duration of response was 10.3 months (95% CI = 7.3–15.2 months). Among the 11 patients with objective responses, 73% had a duration of response lasting at least 6 months, and 27% had a duration of response lasting at least 12 months.
The dordaviprone prescribing information includes warnings and precautions for hypersensitivity, QTc interval prolongation, and embryofetal toxicity. For adults, the recommended dordaviprone dosage is 625 mg orally once weekly. For pediatric patients, the recommended dosage is based on body weight.
Immunotherapy for Refractory Multiple Myeloma: On July 2, the FDA granted accelerated approval to linvoseltamab-gcpt (Lynozyfic), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Efficacy was evaluated in LINKER-MM1, an open-label, multicenter, multicohort trial. The trial excluded patients with prior BCMA-directed bispecific antibody therapy, prior bispecific T-cell–engaging therapy, or prior BCMA chimeric antigen receptor T-cell therapy. The efficacy population included 80 patients who had received at least four prior lines of therapy.
Efficacy was based on objective response rate determined by a blinded independent review committee using International Myeloma Working Group criteria. The objective response rate was 70% (95% CI = 59%–80%). With a median follow-up of 11.3 months among responders, the estimated duration of response was 89% (95% CI = 77%–95%) at 9 months and 72% (95% CI = 54%–84%) at 12 months.
The linvoseltamab-gcpt prescribing information includes a boxed warning for life-threatening cytokine-release syndrome and neurologic toxicity. Linvoseltamab-gcpt is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). For additional information, visit FDA.gov.
