The United States Food and Drug Administration (FDA) granted approvals to five therapeutic agents for the treatment of solid and hematologic cancers and recognized a portion of the Memorial Sloan Kettering database of molecular tumor marker information.

• Atezolizumab as Adjuvant Treatment for Stage II – IIIA NSCLC. Approval was granted to atezolizumab (Tecentriq®, Genentech, Inc.) for adjuvant treatment after surgery and platinum-based chemotherapy in patients with stage II – IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression ≥ 1% of tumor cells. The approval was based on results from the randomized, multicenter, open-label, phase III IMpower010 trial, which showed an improvement in disease-free survival (DFS) with atezolizumab treatment compared with best supportive care in patients with stage II – IIIA NSCLC with PD-L1 expression ≥ 1% of tumor cells (median DFS was not reached vs. 35.3 months, respectively; hazard ratio [HR], 0.66; P=0.0039). The companion diagnostic VENTANA PD-L1 (SP263) Assay (Ventana Medical Systems, Inc.) was approved simultaneously to select patients for treatment with atezolizumab.

• Two Indications for Pembrolizumab in Advanced Cervical Cancer:
  In Combination With Chemotherapy With or Without Bevacizumab as First-Line Treatment. Pembrolizumab (Keytruda®, Merck) was approved in combination with chemotherapy with or without bevacizumab as first-line treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (combined positive score [CPS] ≥1), as determined by a previously FDA-approved test. Results from the randomized, multicenter, double-blind, placebo-controlled, phase III KEYNOTE-826 trial supported the approval. In the trial, the median overall survival (OS) for patients whose tumors expressed PD-L1 (CPS ≥1) was not reached with pembrolizumab vs. 16.3 months with placebo (HR, 0.64; P=0.0001); median progression-free survival was 10.4 months vs. 8.2 months, respectively (HR, 0.62; P<0.0001).
  Single-Agent Treatment. A regular approval was also granted to pembrolizumab as single-agent treatment for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, whose tumors express PD-L1 (CPS ≥1), as determined by the FDA-approved companion diagnostic, PD-L1 IHC 22C3 pharmDx (Dako North America Inc.).

• Adjuvant Abemaciclib Plus Endocrine Therapy for High-Risk, HR-Positive Early Breast Cancer. Approval was given to abemaciclib (Versenio™, Eli Lilly and Company) with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant therapy of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%, as determined by the simultaneously approved companion diagnostic, Ki67 IHC MIB-1 pharmDx (Dako Omnis) assay (Agilent, Inc.). The approval was based on efficacy results from the open-label, randomized, two-cohort, multicenter, phase III monarchE trial, which demonstrated an invasive disease-free survival (IDFS) rate at 36 months of 86.1% for patients who received 2 years of abemaciclib plus standard endocrine therapy vs. 79.0% for patients who had endocrine therapy alone. OS data are immature, follow-up is ongoing.

• Brexucabtagene Autoleucel for Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. The CD-19-directed chimeric antigen receptor (CAR) T-cell immunotherapy, brexucabtagene autoleucel (Tecartus®, Kite Pharma, Inc.) was approved for the treatment of patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. The efficacy of this CAR T-cell therapy was evaluated in the single-arm, multicenter ZUMA-3 trial in which patients received a single infusion of brexucabtagene autoleucel after completion of lymphodepleting chemotherapy. Updated results from this trial showed that at a median follow-up of 16.5 months, brexucabtagene autoleucel elicited a complete response/complete response with incomplete blood count recovery (CR/CRi) in 70.9% of patients, with 56.4% reaching CR. The median duration of remission was 12.8 months. The prescribing information for brexucabtagene autoleucel includes a boxed warning for cytokine-release syndrome and neurologic toxicities.

• Two Distinct Indications for Asciminib in Ph+ CML: Asciminib (Scemblix®, Novartis AG) was granted accelerated approval for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase, previously treated with two or more tyrosine kinase inhibitors (TKIs), and also for patients with Ph+ CML in chronic phase with the T315I mutation.
  Patients With Ph+ CML in Chronic Phase With ≥2 Prior TKIs. This approval was based on the results from the multicenter, randomized, active-controlled, open-label, phase III ASCEMBL trial. At 24 weeks, the major molecular response (MMR) was 25.5% in patients treated with asciminib vs. 13.2% for patients receiving bosutinib. The median duration of MMR has not been reached at a median duration of follow-up of 20 months.
  Patients With Ph+ CML in Chronic Phase With T315I Mutation. Results from the multicenter, open-label, phase I CABL001X2101 trial supported the approval in patients with a T315I mutation. Updated results showed that, by 24 weeks, MMR was achieved by 42% of patients, and by 96 weeks, MMR was achieved by 49% of patients. The median duration of treatment was 108 weeks.
  
  Recognition of Memorial Sloan Kettering Database of Molecular Tumor Marker Information. The FDA granted recognition to a partial listing of the Memorial Sloan Kettering Cancer Center’s Oncology Knowledge Base (OncoKB) as the first tumor mutation database to be included in the Public Human Variant Databases. The OncoKB databases includes information on specific alterations in 682 genes. A portion of the OncoKB was recognized as a source of valid scientific evidence for Level 2 (clinical significance) and Level 3 (potential clinical significance) biomarkers. Under the FDA’s database recognition program, test developers can use these data to support the clinical validity of tumor profiling tests in premarket submissions.