Hematology/Oncology
Lazcluze (lazertinib)
Lazertinib is indicated in combination with amivantamab for first-line treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.
In the Phase 3 MARIPOSA trial (N = 1074), lazertinib plus amivantamab was superior to osimertinib as first-line treatment. Median progression-free survival in the lazertinib-amivantamab group was 23.7 months compared with 16.6 months for osimertinib (P < 0.001). N Engl J Med. 2024 Jun 26
Lymphir (denileukin diftitox)
Denileukin diftitox is indicated for adults with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. It is an Interleukin-2 (IL-2)-diphtheria toxin fusion protein that, after binding to IL-2, depletes immunosuppressive regulatory T lymphocytes (Tregs) and exhibits antitumor activity through direct cytocidal action on IL-2-expressing tumors. It is a reformulation of denileukin (Ontak) that was withdrawn from the market owing to manufacturing problems. Blood. 2022;140(suppl1). Presented at American Society of Hematology annual meeting.
Voranigo (vorasidenib)
Vorasidenib is indicated in patients aged 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or IDH2 mutation, following surgery including biopsy, sub-total resection, or gross total resection. Vorasidenib inhibits IDH1 and IDH2, resulting in decreased production of 2-hydroxyglutarate (2-HG) and partially restores cellular differentiation based on cell-based and in vivo tumor models.
Approval was supported by the Phase 3 INDIGO trial (N = 331). Patients received oral vorasidenib (n = 168) or matched placebo (n = 163). Progression-free survival was significantly improved with vorasidenib compared with placebo (27.7 months vs 11.1 months; P < 0.001). N Engl J Med. 2023 Aug 17;389(7):589-601
Tecelra (afamitresgene autoleucel)
Afamitresgene autoleucel is indicated for unresectable or metastatic melanoma-associated antigen A4 (MAGE-A4)-positive synovial sarcoma in adults who are HLA-A*02:01P, HLA-A*02:02P, HLA-A*02:03P, or HLA-A*02:06P positive and have received prior chemotherapy. It is a MAGEA4-directed genetically modified autologous T-cell immunotherapy.
In the open-label, Phase 2 SPEARHEAD-1 trial, 44 patients with cytogenetically confirmed synovial sarcoma (n = 44) received afamitresgene autoleucel. Overall response rate was 39%. Adverse effects included cytokine release syndrome and cytopenias. Lancet. 2024 Apr 13;403(10435):1460-1471
Niktimvo (axatilimab)
Axatilimab is indicated for refractory chronic graft vs host disease (cGVHD) in adult and pediatric patients (weight at least 40 kg) who are allogeneic hematopoietic stem cell transplantation (HSCT) recipients and have received two prior therapies for cGVHD. It is a monoclonal antibody that targets colony stimulating factor-1 receptor (CSF-1R), a cell surface protein thought to control survival and function of monocytes and macrophages.
Among 239 patients treated with axatilimab for refractory cGVHD in the Phase 2, open-label AGAVE-201 trial, 50-60 patients maintained a duration of response (DOR) for at least 12 months (median DOR was not yet reached). Blood. 2023;142(suppl 1). Presented at American Society of Hematology annual meeting.
Tecentriq Hybreza (atezolizumab/hyaluronidase)
Tecentriq Hybreza is a subcutaneous (SC) formulation of programmed death-ligand 1 (PD-L1) blocker, Tecentriq (atezolizumab). It is indicated in adults with non-small cell lung cancer (NSCLC), small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma.
Approval was based on results from an open-label, multicenter, randomized, Phase 3 (IMscin001) trial (N = 371). Patients with locally advanced or metastatic NSCLC not previously exposed to cancer immunotherapy and who had disease progression following platinum-based chemotherapy were randomized (2:1) to atezolizumab/hyaluronidase SC or atezolizumab IV until disease progression or unacceptable toxicity. Atezolizumab exposure was not significantly different with atezolizumab/hyaluronidase SC compared with atezolizumab IV (geometric mean ratio AUC(0-21d) = 0.87 [90% CI, 0.83-0.92]). Overall response rate (12% vs 10%) and progression-free survival (HR = 1.08 [95% CI, 0.82-1.41]) were similar in both treatment arms. Ann Oncol. 2023 Aug;34(8):693-702
Other hematology/oncology approvals
Imfinzi (durvalumab) – New indication for neoadjuvant/adjuvant resectable non-small cell lung cancer (NSCLC)
Rybrevant (amivantamab) – New indication in combination with carboplatin and pemetrexed for adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor
Kisqali (ribociclib) and Kisqali/Femara Copack (ribociclib/letrozole) – FDA-approved for earlier adjuvant treatment of HR+/HER2-negative breast cancer
Keytruda (pembrolizumab) – New indication approved for first-line treatment of malignant pleural mesothelioma in combination with pemetrexed and platinum chemotherapy
Jemperli (dostarlimab) – Indicated with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer
Darzalex Faspro (daratumumab/hyaluronidase) – New indication for induction and consolidation in patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT) in combination with bortezomib, lenalidomide and dexamethasone
Sarclisa (isatuximab) – New indication in combination with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma in patients who are ineligible for ASCT
Tagrisso (osimertinib) – New indication approved after chemoradiotherapy in stage III EGFR-mutated non-small cell lung cancer
Retevmo (selpercatinib) – FDA grants full approval for RET-mutant medullary thyroid cancer (MTC) in patients aged 2 years and older
Fibryga (fibrinogen, human) – New indication for fibrinogen supplementation for bleeding in patients with acquired fibrinogen deficiency
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Cite this: Mary L WIndle, Amy Hemstreet. FDA Drug Approvals Q3 2024 - Medscape - Oct 14, 2024.
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