Shooting Cancer Highlights – Periodic focus on regulatory status of new targeted therapies in oncology

EMA

• December 30 – Lazertinib + amivantamab – NSCLC EGFR. The European Commission (EC) has approved a Type II variation extension of indication for amivantamab (anti-EGFR-MET bispecific antibody), in combination with lazertinib (third-generation EGFR tyrosine kinase inhibitor), for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R substitution mutations.

CHMP

• November 14 – Repotrectinib – Solid Tumours NTRK / NSCLC ROS1. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a conditional marketing authorisation for the next-generation ROS1/TRK/ALK TKI inhibitor, intended for the treatment of patients whose solid tumours have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, or patients with ROS1-positive advanced non-small cell lung cancer (NSCLC).
• November 14 – Lazertinib + amivantamab – NSCLC EGFR. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for lazertinib (third-generation EGFR tyrosine kinase inhibitor) for the first-line treatment of adult patients with non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations in combination with amivantamab (anti-EGFR-MET bispecific antibody).
• November 14 – Nivolumab + ipilimumab – CRC MSI. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for nivolumab (anti-PD-1 antibody) and ipilimumab (CTLA-4 blocking antibody). The change is concerning the Mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC). The combination nivolumab + ipilimumab would be indicated for first-line treatment of adult patients with unresectable or metastatic colorectal cancer and for treatment of metastatic colorectal cancer after prior fluoropyrimidine based combination chemotherapy.
• November 14 –  Osimertinib – NSCLC EGFR. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending an extension of the indication for the third-generation EGFR TKI. Osimertinib, as monotherapy will be indicated also for the treatment of adult patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations and whose disease has not progressed during or following platinum based chemoradiation therapy.

FDA

• November 15 – Revumenib – AL KMT2A. The Food and Drug Administration (FDA) has approved the first and only menin inhibitor for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.
• December 4 – Zenocutuzumab – NSCLC/PAAD NRG1. The Food and Drug Administration (FDA) granted accelerated approval to the HER2xHER3 bispecific antibody for adults with the following:
  -advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) harbouring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy, or
  -advanced, unresectable, or metastatic pancreatic adenocarcinoma (PAAD) harbouring a NRG1 gene fusion with disease progression on or after prior systemic therapy.
  This represents the first FDA approval of a systemic therapy for patients with NSCLC or pancreatic adenocarcinoma harbouring an NRG1 gene fusion.
• December 18 – Ensartinib – NSCLC ALK. The Food and Drug Administration (FDA) has approved the ALK tyrosine kinase inhibitor for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK-TKI.
• December 20 – Encorafenib – CRC BRAF. The Food and Drug Administration (FDA) granted accelerated approval to the BRAF inhibitor with cetuximab and mFOLFOX6 for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test.
• December 3 – Sacituzumab tirumotecan – NSCLC EGFR. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to the trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) for the treatment of patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations (exon 19 deletion [ex19del] or exon 21 L858R) whose disease progressed on or after tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy.
• December 9 – Datopotamab deruxtecan – NSCLC EGFR. The Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to the TROP2-directed ADC for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) with disease progression on or after treatment with an EGFR-tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy.
• December 12 – IMM-1-104 – CM NRAS. The Food and Drug Administration (FDA) has granted Fast Track Designation to the new MEK inhibitor, as a treatment for patients with unresectable or metastatic NRAS-mutant cutaneous melanoma (CM) who have progressed on or are intolerant to PD-1/PD-L1 based immune checkpoint inhibitors.
• December 16 – Dostarlimab – RC MSI. The Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to the anti-PD-1 monoclonal antibody for the treatment of patients with locally advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer.
• December 23 – Taletrectinib – NSCLC ROS1. The Food and Drug Administration (FDA) has granted priority review to the next-generation selective ROS1/NTRK inhibitor, for the treatment of patients with ROS1-rearranged (ROS1+) advanced non–small cell lung cancer (NSCLC).
• December 30 – Avutometinib + defactinib – LGSOC KRAS. The Food and Drug Administration (FDA) has granted priority review to the New Drug Application (NDA) for avutometinib, an oral RAF/MEK clamp, in combination with defactinib, an oral FAK inhibitor, for the treatment of adult patients with recurrent low-grade serous ovarian cancer (LGSOC), who received at least one prior systemic therapy and have a KRAS mutation.