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FDA Cancer Treatment Approvals in September 2021

In September, the United States Food and Drug Administration (FDA) granted six new and extended indications for the treatment of patients with solid tumors or hematologic cancers, including one for patients with chronic graft-versus-host disease (cGVHD).

  • Mobocertinib for Advanced EGFR Exon 20 Insertion Positive NSCLC. Mobocertinib (ExkivityTM, Takeda Pharmaceuticals), a first-in-class, oral tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) exon 20 insertion mutations, was granted accelerated approval for the treatment of patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy. The results from the international, non-randomized, open-label, multicohort phase I/II Study 101 supported the approval, showing an overall response rate (ORR) of 28%, with a median response duration of 17.5 months. The companion diagnostic Oncomine Dx Target Test (Thermo Fisher Scientific) was approved simultaneously for the detection of EGFR exon 20 insertion mutations in patients with advanced NSCLC. The prescribing information includes a boxed warning for QTc prolongation and Torsades de Pointes, and warnings for interstitial lung disease/pneumonitis, cardiac toxicity, and diarrhea.

  • Cabozantinib for Advanced Differentiated Thyroid Cancer. Approval was given to cabozantinib (Cabometyx, Exelixis, Inc.) for patients ≥12 years with locally advanced or metastatic differentiated thyroid cancer that has progressed following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy and who are ineligible or refractory to radioactive iodine. The approval was supported by efficacy results from the randomized, double blind, placebo-controlled, multicenter, phase III COSMIC-311 trial. Updated results showed a significant improvement in progression-free survival (PFS) for cabozantinib- versus placebo-treated patients (11.0 months versus 1.9 months; P<0.0001), which was irrespective of prior exposure to lenvatinib and/or sorafenib. The ORR was 11% versus 0%, respectively.

  • Tisotumab Vedotin, an Antibody Drug Conjugate, for Advanced Cervical Cancer. Accelerated approval was granted to tisotumab vedotin-tftv (TivdakTM, Seagen Inc.), a tissue factor-directed antibody and microtubule inhibitor conjugate, for patients with recurrent or metastatic (R/M) cervical cancer with disease progression on or after chemotherapy. Approval was based on efficacy results from the open-label, multicenter, single-arm, phase II innovaTV 204 trial in which tisotumab vedotin demonstrated an ORR of 24%, with 7% complete responses and a median duration of response (DoR) of 8.3 months in patients with R/M cervical cancer who had received no more than two prior systemic regimens in the R/M setting with at least one platinum-based chemotherapy regimen (with bevacizumab if eligible).
  • Zanubrutinib, a Novel Bruton Tyrosine (BTK) Inhibitor, Approved in Two Indications:
    Marginal zone lymphoma (MZL). Accelerated approval was granted to zanubrutinib (Brukinsa®, BeiGene) for the treatment of patients with relapsed or refractory (R/R) MZL who have received at least one anti-CD20-based regimen. The approval was based on results from two open-label, multicenter, single-arm studies in which patients received zanubrutinib monotherapy. In the recently published phase II MAGNOLIA trial, which included patients who had received at least one anti-CD20-based regimen, the ORR was 68.2%, with 25.8% of patients achieving complete response; the estimated 12-month DoR rate was 93%, and median progression free survival (PFS) was not reached. In the phase I/II BGB-3111-AU-003 trial, which included 20 patients with previously treated MZL, the ORR was 80%, with a CR rate of 15%, and the estimated 18-month DoR rate was 66%.

    Waldenström’s Macroglobulinemia (WM). Zanubrutinib was also approved for patients with WM. This is based on results from the randomized, active-controlled, open-label, phase III ASPEN trial which evaluated the efficacy of zanubrutinib, based on the presence or absence of MYD88 L265P mutation, in two cohorts of patients with WM. In the first cohort, patients with MYD88 L265P mutated WM were randomized to receive either zanubritinib or ibrutinib. In the second cohort, patients with MYD88 wild-type or MYD88 mutation unknown WM all received zanubrutinib. The major response rate (MRR: complete response, very good partial response, and partial response) for patients in cohort 1 was 77.5% with zanubrutinib and 78% with ibrutinib, with an event-free rate at 18 months of 85% and 88%, respectively. For cohort 2, the MRR was 50% with an event-free rate at 12 months of 72.4%. Note, approval was based on a non-comparative assessment of response and DoR from the zanubrutinib arms.
  • Ruxolitinib for cGVHD. Chronic GVHD continues to be a major complication after allogeneic hematopoietic cell transplantation. Selective JAK1/2 inhibitor ruxolitinib (Jakafi® Incyte Corp.) was granted approval for cGVHD after failure of one or two lines of systemic therapy in patients ≥12 years, based on efficacy results from the randomized, open-label, multicenter phase III REACH-3 trial. In the trial, patients received either ruxolitinib or best available therapy (BAT) for corticosteroid-refractory cGVHD after allogeneic stem cell transplantation. Updated results used by the FDA showed the ORR was 70% for the ruxolitinib arm versus 57% for the BAT arm, and the median DoR was 25 months and 5.6 months, respectively.