Delcath Systems has announced it has submitted a new drug application (NDA) resubmission to the US Food and Drug Administration (FDA) for the Hepzato Kit (melphalan hydrochloride for injection/hepatic delivery system, or melphalan/HDS) seeking approval for the treatment of patients with unresectable hepatic-dominant metastatic ocular melanoma (mOM).
The resubmission is in response to a Complete Response Letter (CRL) from the US FDA. The NDA resubmission contains comprehensive data and information to address all issues identified in the CRL. The US FDA is expected to determine whether the resubmission constitutes a complete response and is eligible for review within 30 days. Once accepted for review by the US FDA, a new prescription drug user fee amendments (PDUFA) action date will be established for the Hepzato Kit application.
The FOCUS trial
The FOCUS trial evaluated the safety and efficacy of treatment with Hepzato Kit for patients with mOM. The primary endpoint of overall response rate (ORR) was assessed by an independent review committee per RECIST (Response evaluation criteria in solid tumours) version 1.1. Per protocol, patients were treated every six to eight weeks for a maximum of six cycles. Tumour responses were assessed every 12 weeks (+/- 2 weeks) until disease progression.
As previously reported, treatment with Hepzato Kit in the treated population resulted in an ORR of 36.3% (95% confidence interval [CI]: 26.44, 47.01) including 7.7% of patients with a complete response (CR). The median duration of response was 14 months (95% CI: 8.31, 17.74) and the disease control rate (DCR) was 73.6% (95% CI: 63.35, 82.31).
In addition, the NDA resubmission includes updated estimated median overall survival (OS) of 20.53 months (95% CI: 16.79, 25.26) and updated estimated OS at one year of 0.80 (95% CI: 0.70, 0.87). Delcath Systems will continue to follow patients until May 2023 (24 months after the last patient’s last treatment).
There were no treatment-related deaths in the trial. This is consistent with Chemosat, the HDS device component of Hepzato Kit, approved in Europe under a CE mark to deliver melphalan to the liver. The safety data submitted in the NDA is consistent with the Chemosat safety data documented in numerous European single-centre and multicentre publications.