FDA Approves Yervoy Treatment For Melanoma To Treat Pediatric Patients

Immuno-oncologygiant Bristol-Myers Squibb announced that the U.S. Food and Drug Administration(FDA) has expanded the indication for Yervoy intravenous solution for the treatment of pediatric patients 12 years of age and older with unresectable ormetastatic melanoma. It is worth mentioning that the FDA approval of yervoytreatment for melanoma aged 12 years and older also marks the first pediatricindication for Bristol-Myers’ immuno-oncology drug.

Yervoyis a recombinant human monoclonal antibody that blocks cytotoxic Tlymphocyte-associated antigen 4 (CTLA-4). CTLA-4 is a negative regulator of Tcell activation. Yervoy can block the interaction between CTLA-4 and itsligands CD80/CD86 after binding to CTLA-4. Blockade of CTLA-4 has been shown toenhance T cell activation and proliferation. The mechanism of action of Yervoyin melanoma patients is indirectly through the anti-tumor immune responsemediated by T cells. Therefore, unlike the traditional treatment principle,Yervoy does not directly kill cancer cells, but exerts anti-cancer effects bystimulating the body's immune system. This drug is given intravenously.

Yervoy treatment for melanoma has evaluated efficacy and safety in pediatric patientsin 2 studies: a dose-finding study in 33 patients aged 2-21 years with relapsedor refractory solid tumors, and a single-arm study It was performed in 12adolescent patients (age range: 12-16 years) with previously treated oruntreated, unresectable stage III or IV malignant melanoma. In pediatric andadolescent patients, the overall safety profile of yervoy treatment formelanoma was consistent with that in adults, and the drug's similarity inadults and pediatric patients 12 years of age and older allowed extrapolationof the data. Based on a population pharmacokinetic analysis, the exposure ofYervoy in adolescents 12 years and older was comparable to the approved 3 mg/kgin adults, given as an intravenous infusion over 90 minutes every 3 weeks for atotal of 4 treatments agent.

In the United States, the FDA approved yervoy treatment for melanoma monotherapyin March 2011 for the treatment of adult patients with unresectable ormetastatic melanoma, and since its launch, more than 38,000 adult patientsworldwide have received Yervoy treatment. In addition, Yervoy is indicated asadjuvant therapy in patients with cutaneous melanoma with pathologicalinvolvement of regional lymph nodes greater than 1 mm who have undergonecomplete resection, including total lymphadenectomy. On April 6, the FDA issueda statement emphasizing that the FDA has developed a Risk Evaluation andMitigation Strategy (REMS) to promote the safe use of the newly approvedchemotherapy drug Yervoy. Yervoy is approved for the treatment of patients withnewly diagnosed melanoma, or previously treated patients with unresectable ormetastatic melanoma. The REMS was formulated for Yervoy to ensure that thebenefits of Yervoy outweigh its associated risk of immune-mediated severe,fatal adverse reactions. REMS consists of a communication plan that includesinforming medical personnel of the serious risks of Yervoy, facilitating earlydetection of these risks, and a summary of recommended management for patientswith immune-mediated moderate and severe adverse reactions.

Thelabeling for Yervoy has a boxed warning stating that use of the drug may resultin immune-mediated severe, fatal adverse events that may be caused by T cellactivation and proliferation. Such immune-mediated reactions can involve anyorgan system, but the most common severe immune-mediated adverse reactions arecolitis, hepatitis, dermatitis (including toxic epithelial necrolysis),gastrointestinal bleeding or perforation, severe exercise, and Sensory neuropathy,immune-mediated eye disease unresponsive to topical immunosuppressive therapy,and endocrine disease. In clinical trials, most of the immune-mediated adversereactions described above occurred during treatment, but a few occurred weeksto months after Yervoy was discontinued.

Inpatients with severe immune-mediated reactions, it is recommended topermanently discontinue Yervoy and initiate systemic high-dose corticosteroidtherapy, and all patients receiving Yervoy should also be evaluated forcolitis, dermatitis, neuropathy, and endocrine Symptoms and signs of disease.In addition, clinical tests, including liver function and thyroid functiontests, should be performed at baseline and prior to each dose of the drug forthose receiving Yervoy.

Atthe same time, in October 2015, Opdivo and Yervoy combination therapy (OY) wasapproved as the first I-O combination therapy for the treatment of metastaticmelanoma, and this indication has been approved in more than 50 countriesaround the world. Up to now, the approved indications of the OY combinationare: ①treatment of patients with unresectable or metastatic melanoma; ②first-linetreatment of patients with intermediate and high-risk advanced renal cellcarcinoma; ③treatment of patients 12 years of age and older Microsatelliteinstability-high or mismatch repair deficient metastatic colorectal cancer inpediatric and adult patients.

Thissignificant change in the treatment modalities of yervoy treatment for melanomaunderscores the critical role of independent clinical research in specifictumor settings.