The OncFive: Top Oncology Articles for the Week of 12/15

Welcome to OncLive®’s OncFive! Every week, we will compile the top 5 stories in oncology, ranging from pivotal regulatory decisions to news updates and expert interviews spanning tumor types.

Here’s what you may have missed this week:

FDA Grants Accelerated Approval to Encorafenib Combo for BRAF V600E+ Metastatic CRC

The regulatory agency has awarded accelerated approval to encorafenib (Braftovi) paired with cetuximab (Erbitux) and fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for the treatment of patients with metastatic colorectal cancer with a BRAF V600E mutation based on findings from the phase 3 BREAKWATER study (NCT04607421). The combination (n = 158) induced an objective response rate (ORR) of 61% (95% CI, 52%-70%) vs 40% (95% CI, 31%-49%) with chemotherapy with or without bevacizumab (Avastin; n = 243; P = .0008). The median duration of response in the respective arms was 13.9 months (95% CI, 8.5-not estimable [NE]) and 11.1 months (95% CI, 6.7-12.7). This is the first and only combination regimen featuring a BRAF-targeted therapy for this population.

FDA Approves Ensartinib for Locally Advanced or Metastatic ALK+ NSCLC

Ensartinib (Ensacove) has been approved by the FDA for use in adult patients with ALK-positive locally advanced or metastatic non–small cell lung cancer (NSCLC) who did not have prior exposure to ALK inhibition. Findings from the phase 3 eXALT3 study (NCT02767804) showed that the median progression-free survival with ensartinib was 25.8 months (95% CI, 21.8-NE) vs 12.7 months (95% CI, 9.2-16.6) with crizotinib (Xalkori), translating to a 44% reduction in the risk of disease progression or death (HR, 0.56; 95% CI, 0.40-0.79; P = .0007). No statistically significant difference in overall survival was observed between the treatment arms (HR, 0.88; 95% CI, 0.63-1.23; P = .4570).

FDA Issues a CRL to Subcutaneous Amivantamab BLA in EGFR+ NSCLC

The regulatory agency issued a complete response letter to the biologics license application seeking the approval of fixed-combination amivantamab-vmjw (Rybrevant) and recombinant human hyaluronidase for subcutaneous administration in patients with NSCLC harboring EGFR exon 19 deletions or L858R substitution mutations. The letter followed observations made during a standard pre-approval inspection at a manufacturing facility and was not related to product formulation or safety or efficacy data in the application. The FDA did not request any additional clinical studies and does not impact the approval of the intravenous formulation.

EU Approval Sought for Frontline Ibrutinib Plus R-CHOP in Mantle Cell Lymphoma

Johnson & Johnson has submitted a type II variation application to the European Medicines Agency that is seeking approval for an indication extension of ibrutinib (Imbruvica) paired with rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) in adult patients with treatment-naive mantle cell lymphoma who are eligible for autologous stem cell transplant. The application is based on findings from the phase 3 TRIANGLE study (NCT02858258) in which the ibrutinib regimen (n = 292) led to a 4-year failure-free survival (FFS) rate of 82% vs 70% with R-CHOP alone (n = 292). At a median follow-up of 55 months, the median FFS was not reached in either arm (HR, 0.64; P = .0026).

FDA Grants Breakthrough Therapy Designation to Sacituzumab Govitecan for Second-Line ES-SCLC

The regulatory agency has granted breakthrough therapy designation to sacituzumab govitecan-hziy (Trodelvy) for use as a potential option in patients with extensive-stage small cell lung cancer (ES-SCLC) who disease has progressed on or following platinum-based chemotherapy. This decision is supported by data from the ES-SCLC cohort of the phase 2 TROPiCS-03 trial (NCT03964727). The antibody-drug conjugate elicited an ORR of 41.9% (95% CI, 27.0%-57.9%). The disease control rate was 83.7% (95% CI, 69.3%-93.2%) and the clinical benefit rate was 48.8% (95% CI, 33.3%-64.5%).