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April 24, 2020
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FDA grants priority review to several therapies

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The FDA granted priority review to the following therapies in development for oncology and hematology indications:

  • Olaparib (Lynparza; AstraZeneca, Merck), a poly(ADP-ribose) polymerase (PARP) inhibitor, for treatment of men with metastatic castration-resistant prostate cancer and homologous recombination repair gene mutations who progressed on treatment with a new hormonal agent.

Results of the randomized phase 3 PROfound study showed significantly longer median radiographic PFS among men with BRCA1/BRCA2- or ATM-mutated metastatic castration-resistant prostate cancer assigned olaparib vs. physician’s choice of enzalutamide (Xtandi; Astellas, Pfizer) or abiraterone acetate (Zytiga, Janssen; 7.4 months vs. 3.6 months; HR = 0.34; 95% CI, 0.25-0.47).

Olaparib also was associated with longer radiographic PFS among the overall population of men with homologous recombination repair-mutated disease, including those with BRCA1/BRCA2, ATM, CDK12 or 11 other mutations (5.8 months vs. 3.5 months; HR = 0.49; 95% CI, 0.38-0.63).

  • Belantamab mafodotin (GSK2857916, GlaxoSmithKline), an investigational anti-B-cell maturation antigen monoclonal antibody-drug conjugate, for treatment of patients with relapsed or refractory multiple myeloma who previously received an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.

Results of the DREAMM-2 study showed belantamab mafodotin induced response rates of 31% to 34% among heavily pretreated patients depending on dose.

  • Rucaparib (Rubraca, Clovis Oncology), a PARP inhibitor, as monotherapy for men with BRCA1/BRCA2-mutant recurrent, metastatic castration-resistant prostate cancer.

Approximately 12% of men with metastatic castration-resistant prostate cancer harbor deleterious germline and/or somatic mutations in BRCA1 or BRCA2. These mutations can be used to guide patient selection for treatment with PARP inhibitors.

  • Brigatinib (Alunbrig, Takeda), a selective next-generation tyrosine kinase inhibitor, as first-line treatment for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer.

The randomized phase 3 ALTA-1L trial compared the efficacy and safety of brigatinib with crizotinib (Xalkori, Pfizer) for patients with ALK-positive locally advanced or metastatic NSCLC who had not received prior treatment with an ALK inhibitor.

Results showed a significant median PFS benefit with brigatinib as determined by blinded independent review (24 months vs. 11 months; HR = 0.49; 95% CI, 0.35-0.68) and investigator assessment (29.4 months vs. 9.2 months; HR = 0.43; 95% CI, 0.31-0.61).

Results also showed a significantly higher confirmed ORR (74% vs. 62%; P = .0342) and longer median duration of response (not estimable vs. 14 months) in the brigatinib group.

  • Ripretinib (Deciphera Pharmaceuticals), a tyrosine kinase switch control inhibitor engineered to broadly inhibit KIT and platelet-derived growth factor receptor alpha-mutated kinases, for treatment of advanced gastrointestinal stromal tumors (GIST).

The randomized phase 3 INVICTUS study included 129 patients with advanced GIST who underwent prior treatment with imatinib, sunitinib (Sutent, Pfizer) and regorafenib (Nexavar, Bayer).

The study achieved its primary endpoint, as patients assigned ripretinib as fourth-line or later treatment achieved significantly longer PFS than those assigned placebo.

  • Tazemetostat (Tazverik, Epizyme), a methyltransferase inhibitor, for treatment of patients with relapsed or refractory follicular lymphoma.

Tazemetostat already is approved in the United States for treatment of patients aged 16 years or older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.

Epizyme seeks accelerated approval of the agent for treatment of patients with follicular lymphoma who received at least two prior lines of systemic therapy.

Results of a phase 2 study showed tazemetostat conferred clinical benefit and appeared generally well-tolerated by patients with follicular lymphoma who had EZH2 activating mutations and those with EZH2 wild-type disease.

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  •  Tucatinib (Seattle Genetics), an investigational oral tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR, for use in combination with trastuzumab (Herceptin, Genentech) and capecitabine, for treatment of patients with locally advanced or metastatic HER2-positive breast cancer.

This indication applies to patients regardless of whether they have brain metastases who received at least three prior HER2-directed agents alone or in combination in any treatment setting.

The HER2CLIMB study evaluated the addition of tucatinib to trastuzumab plus capecitabine among 612 patients with locally advanced or metastatic HER2-positive breast cancer who received prior treatment with trastuzumab, pertuzumab (Perjeta, Genentech) and ado-trastuzumab emtansine (Kadcyla, Genentech).

Results showed the addition of tucatinib to trastuzumab and capecitabine conferred a statistically significant improvement in PFS (median, 7.8 months vs. 5.6 months; HR = 0.54; 95% CI, 0.42-0.71), including among patients with brain metastases (median, 7.6 months vs. 5.4 months; HR = 0.48; 95% CI, 0.34-0.69).

Tucatinib appeared associated with a 34% reduction in risk for death (median OS, 21.9 months vs. 17.4 months; HR = 0.66; 95% CI, 0.5-0.88) and a significantly higher overall response rate (41% vs. 23%; P = .00008).