Three agents receive breakthrough therapy designation
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The FDA granted breakthrough therapy designation to three agents in development for oncology indications.
They include:
- Debio 1143 (Debiopharm) for first-line treatment of head and neck cancer.
The designation applies to use of Debio 1143 — a novel inhibitor of apoptosis proteins antagonist — in combination with standard cisplatin-based concomitant standard fractionation chemoradiation for patients with previously untreated, unresectable locally advanced head and neck squamous cell carcinoma.
Phase 2 study results showed the combination of Debio 1143 and chemoradiation improved locoregional control by 21% at 18 months and improved 2-year PFS (HR = 0.37; P = .007) compared with placebo plus chemoradiation. The agent also exhibited a manageable safety profile.
No new therapies have been approved in the past 25 years for patients with locally advanced head and neck squamous cell carcinoma.
- Enfortumab vedotin-ejfv (Padcev; Astellas Pharma, Seattle Genetics) for advanced bladder cancer.
The designation applies to use of the agent in combination with pembrolizumab (Keytruda, Merck) for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are ineligible for first-line cisplatin-based chemotherapy.
Enfortumab vedotin-ejfv is an antibody-drug conjugate directed against the nectin-4 protein on the surface of cancer cells.
The FDA granted breakthrough therapy designation based on results of the dose-escalation cohort and expansion cohort A of the phase 1b/phase 2 EV-103 trial, in which patients with advanced or metastatic urothelial cancer who were ineligible for cisplatin-based chemotherapy received the first-line combination of enfortumab vedotin-ejfv plus pembrolizumab.
Results showed an objective response rate of 73.3% for the combination therapy, including a 15.6% complete response rate and 93.3% disease control rate. The most common treatment-related adverse events included fatigue, experienced by 58% of patients (11% grade 3), alopecia (53%) and peripheral sensory neuropathy (53%; 4% grade 3).
- JNJ-6372 (Janssen) for treatment of patients with metastatic non-small cell lung cancer who have epidermal growth factor receptor exon 20 insertion mutations and whose disease progressed on or after platinum-based chemotherapy.
JNJ-6372 is a dual-targeting EGFR-mesenchymal epithelial transition (MET) factor bispecific antibody. The agent targets activating and resistant EGFR and MET mutations and amplifications.
There are no FDA-approved targeted therapies for patients with lung cancer who have EGFR exon 20 insertion mutations. Standard treatment for these patients is conventional cytotoxic chemotherapy.
The FDA based the breakthrough therapy designation in part on data from a phase 1 study designed to evaluate JNJ-6372 as monotherapy and in combination with lazertinib (Janssen/Yuhan Corp.) — a novel third-generation EGFR tyrosine kinase inhibitor — for adults with advanced NSCLC.