CHICAGO―Lambrolizumab is safe and exhibits anti-melanoma tumor activity, regardless of previous ipilimumab (IPI) treatment history, according to results of an ongoing phase 1b expansion study presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting and published online by the New England Journal of Medicine.

“Preliminary data suggest that lambrolizumab has significant antitumor activity and is well tolerated with manageable side effects in both IPI-naïve and IPI-pretreated melanoma patients,” reported Antoni Ribas, MD, PhD, of the University of California Los Angeles, and coauthors. The overall response rate across all doses and schedules, as confirmed by central review using RECIST 1.1 criteria, was 38%, the coauthors reported.

Programmed death (PD)-1 is an inhibitory T-cell co-receptor that might suppress antitumor immunity, the coauthors noted. Lambrolizumab is a humanized anti-PD-1 monoclonal IgG4 antibody.

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The coauthors enrolled 135 patients diagnosed with advanced melanoma (87 IPI-naïve patients; 48 IPI-pretreated patients), administering lambrolizumab at 10 mg/kg intravenously every 2 weeks (n=57; 41 ipilimumab-naïve) or 3 weeks (n=56; 24 ipilimumab-naïve), or 2 mg/kg (n=22, all ipilimumab-naïve) every 3 weeks until disease progression or unacceptable toxicity, the coauthors reported.

“Responses were durable in the majority of patients” who experienced response, at a median follow-up of 11 months, the authors reported: 42 (81%) of patients with a response were continuing with treatment as of March 2013. 

The most common drug-related adverse events (AEs), as expected, were fatigue (30.4% all grades; 1.5% grade 3/4), rash (20.7%; 2.2% grade 3/4), and pruritus (20.7%; 0.7% grade 3/4), Dr. Ribas noted. A total of 107 (79%) patients experienced at least one drug-related AE, but most were manageable low-grade fevers and rashes, he said. Only 17 (12.6%) patients experienced a grade 3 or 4 drug-related AE (23% in the 10 mg/kg every 2 weeks group, 4% in the 10 mg/kg every 3 weeks group, and 9% in the 2 mg/kg group), he said.   Patients in the 10 mg/kg every 2 weeks group were on therapy for a median 40.1 weeks, compared to 20.6 weeks and 18.1 weeks among the 10 mg/kg every 3 weeks and the 2 mg/kg every 3 weeks groups, Dr. Ribas noted.

AEs of an inflammatory or immune nature included grade 1/2 pneumonitis in 4.4% of patients and hypothyroidism in 8.1% of patients. (One case of grade 3 hyperthyroidism was seen, and this patient also suffered grade 2 adrenal insufficiency, Dr. Ribas said.)

“Most treatment-related AEs were successfully managed with treatment discontinuation, supporting care and, occasionally, glucocorticoids,” Dr. Ribas said.

Confirmed objective responses were “rapid and durable” among patients who saw a benefit, Dr. Ribas said, adding that it is possible that longer follow-up will reveal objective responses or become partial or even complete responses.

“The longer we wait, it’s possible we will see better responses,” he said.

“These data have led to an ongoing, international, randomized study of lambrolizumab versus chemotherapy in IPI-pretreated melanoma,” Dr. Ribas and his coauthors reported.

The study received support from Merck Sharp and Dohme.