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

EMA

• May 28 – Selpercatinib – Solid Tumours RET. The European Commission (EC) has approved the extension of indication for the RET receptor tyrosine kinase inhibitor to include the treatment, in monotherapy, of adults with advanced or metastatic RET fusion-positive solid tumours with disease progression on or after prior systemic therapies or who have no satisfactory therapeutic options.
• June 19 – Alectinib – NSCLC ALK. The European Commission (EC) has approved the extension of indication for the 2^nd generation ALK tyrosine kinase inhibitor to include the use of alectinib as monotherapy in adult patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) as adjuvant treatment following tumour resection.

 

CHMP

• May 30 – Sugemalimab – NSCLC EGFR/ALK/ROS1/RET The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the anti-PD-L1 monoclonal antibody, intended for the first-line treatment of adults with metastatic non?small?cell lung cancer (NSCLC) with no sensitising EGFR mutations, or ALK, ROS1 or RET genomic tumour aberrations, in combination with chemotherapy.
• May 30 – Osimertinib – NSCLC EGFR. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a new indication for the third-generation EGFR tyrosine kinase inhibitor: first?line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, in combination with pemetrexed and platinum-based chemotherapy.
• May 30 – Tislelizumab – NSCLC PD-L1/EGFR/ALK. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a new indication for the anti-PD-1 monoclonal antibody.

Tislelizumab, in combination with pemetrexed and platinum?containing chemotherapy, is indicated for the first-line treatment of adult patients with non-squamous non-small cell lung cancer whose tumours have PD-L1 expression on ?50% of tumour cells with no EGFR or ALK positive mutations and who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.

Tislelizumab, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of adult patients with squamous non-small cell lung cancer who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.

Tislelizumab as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab.

• June 27 – Erdafitinib – UC FGFR3. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the FGFR tyrosine kinase inhibitor, intended for the treatment of urothelial carcinoma (UC) harbouring susceptible FGFR3 genetic alterations.
• June 27 – Durvalumab – EC MMR. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a new indication: the anti-PD-L1 antibody, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of adults with primary advanced or recurrent endometrial cancer (EC) who are candidates for systemic therapy, followed by maintenance treatment with:

• durvalumab as monotherapy in endometrial cancer that is mismatch repair deficient (dMMR)
• durvalumab in combination with olaparib in endometrial cancer that is mismatch repair proficient (pMMR).

• June 27 – Olaparib – EC MMR. The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a new indication: the PARP inhibitor, in combination with durvalumab, is indicated for the maintenance treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair proficient (pMMR) whose disease has not progressed on first-line treatment with durvalumab in combination with carboplatin and paclitaxel.

 

FDA

• May 29 – Selpercatinib – TC/Solid Tumours RET. The Food and Drug Administration (FDA) granted accelerated approval to the RET receptor tyrosine kinase inhibitor for paediatric patients two years of age and older with the following:

• advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy;
• advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate); and
• locally advanced or metastatic solid tumours with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

• June 12 – Selpercatinib – TC RET. The Food and Drug Administration (FDA) granted traditional approval to the RET receptor tyrosine kinase inhibitor for adult and paediatric patients 2 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Selpercatinib received accelerated approval for this indication for patients 12 years of age and older in 2020.

• June 13 – Repotrectinib – Solid Tumours NTRK. The Food and Drug Administration (FDA) granted accelerated approval to the inhibitor of ROS1 and TRKs tyrosine kinases for adult and paediatric patients 12 years and older with solid tumours that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and that have progressed following treatment or have no satisfactory alternative therapy.
• June 14 – Durvalumab – EC MMR. The Food and Drug Administration (FDA) approved the anti-PD-L1 antibody with carboplatin plus paclitaxel followed by single-agent durvalumab for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).
• June 14 – Blinatumomab – BCP ALL CD19/Ph. The Food and Drug Administration (FDA) approved the BiTE-class (bi-specific T-cell engager) constructed monoclonal antibody for adult and paediatric patients one month and older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukaemia (Ph-negative BCP ALL) in the consolidation phase of multiphase chemotherapy.
• June 21 – Adagrasib – CRC KRAS. The Food and Drug Administration (FDA) granted accelerated approval to the KRAS inhibitor plus cetuximab for adults with KRAS G12C-mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
• May 6 – Zenocutuzumab – NSCLC/PDAC NRG1. The Food and Drug Administration (FDA) has granted priority review to the biologics license application of the HER2 x HER3 bispecific antibody in patients with neuregulin 1 fusion (NRG1+) non-small cell lung (NSCLC) and NRG1+ pancreatic (PDAC) cancer.
• May 16 – NVL-655 – NSCLC ALK. The Food and Drug Administration (FDA) has granted a breakthrough therapy designation to the novel brain-penetrant ALK-selective TKI for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with two or more ALK tyrosine kinase inhibitors (TKIs).
• May 21 – Inavolisib – BC PIK3CA/HR/HER2. The Food and Drug Administration (FDA) has granted a breakthrough therapy designation to the PI3K inhibitor, in combination with palbociclib and fulvestrant, for the treatment of adult patients with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment.
• May 29 – Inavolisib – BC PIK3CA/HR/HER2. The Food and Drug Administration (FDA) has granted priority review to the PI3K inhibitor, in combination with palbociclib and fulvestrant, for the treatment of adult patients with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment.
• May 29 – Zanidatamab – BTC HER2. The Food and Drug Administration (FDA) has granted priority review of the biologics license application for the HER2-targeted bispecific antibody for the treatment of previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC).
• May 29 – AFM24 – NSCLC EGFR. The Food and Drug Administration (FDA) has granted fast track designation to the tetravalent, bispecific innate cell engager (ICE) in combination with atezolizumab for the treatment of patients with advanced and/or metastatic non-small cell lung cancer (NSCLC) not harbouring any activating EGFR mutations (EGFR wild-type) after progression on PD-(L)1 targeted therapy and platinum-based chemotherapy.
• June 10 – Osimertinib – NSCLC EGFR. The Food and Drug Administration (FDA) has granted priority review to the third-generation, irreversible EGFR-TKI for the treatment of adult patients with unresectable, Stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after chemoradiotherapy (CRT). If approved, osimertinib will be indicated for patients whose tumours have EGFR exon 19 deletions or exon 21 (L858R) mutations.
• June 4 – Lunresertib + camonsertib – OC CCNE1/FBXW7/PPP2R1A. The Food and Drug Administration (FDA) has granted fast track designation to lunresertib (PKMYT1 inhibitor) in combination with camonsertib (ATR inhibitor) for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A-mutated platinum-resistant ovarian cancer.