Safety and efficacy of HX008: A humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma—A single-arm, multicenter, phase II study.
Authors: Lian Bin , Chen Yu , Wu Di , Luo Zhiguo , Zou Zhengyun , Jiang Yu , Pan Hongming , Fan Qingxia , Zhao Jianfu , Xu Qing , Jiang Renbing , Cui Chuanliang , Wang Xuan , Lou Fang , Guo Zhen , Si Lu , Chi Zhihong , Sheng Xinan , Guo Jun 
Published: June 2021

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Background: HX008 is a new recombinant humanized anti-PD-1 monoclonal antibody, belonging to human IgG4 / kappa subtype, which can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods: In this single arm phase 2 trial, eligible patients (pts) were aged from18 to 75, who previously failed with conventional treatment for locally advanced or metastatic melanoma, with an ECOG performance status of 0 or 1 and had measurable lesions according to the RECIST criteria (V1.1). Ocular melanoma, brain metastasis or previous use of anti PD-1 ab were excluded. Pts received HX008 3mg/kg every 3 weeks, until disease progression, intolerable toxicity or treatment discontinuation for any other reasons. The primary endpoint was ORR according to RECIST criteria, and the secondary endpoints were OS, PFS, DCR and the toxicity. The iRECIST criteria would also be used in the evaluation of response and treatment discontinuation. Clinical trial information: NCT04749485. Results: From Oct 2018 to Jan 2021, 119 pts have been eligible and enrolled. Basic characteristics: median age 59 years; 57 males (42.9%) ; stage 22%, stage 78%; primary: acral 52.1%, mucosal 19.3%, cutaneous 18.5% and unknown 10.1%; Gene mutation status: Braf 10.9%, Nras 9.2%, cKit 4.2%; condition of previous treatments: 67.26%, 25.21%,7.56% pts had received 1st, 2nd and 3rd line or above treatments respectively (chemotherapy 69.7%, targeted therapy 15.1%, immunotherapy 43.7%). The ORR according to RECIST V1.1 and iRECIST was 18.49% (1CR, 21 PR, 95% CI 11.96-26.64) and 20.17% (1 iCR, 23 iPR,95% CI 13.37-28.50), respectively. For PD-L1 positive pts the ORR was 15.09% (95%CI 6.75-27.60) and 12% for negative (95%CI 10.98-32.83). For different subtypes, the ORR was 36.36% for cutaneous melanoma, 14.52% for acral primary, 8.7% for mucosal primary, and 25% for unknown primary. The DCR and iDCR was 44.54% and 47.06%, respectively. With a median follow up time of 13.2 months, the median PFS was 3.25 months (95% CI 2.0, 4.1) and the PFS rate at 1 year was 25.8% (95%CI 17.19,35.33). The median OS was 17.91 months (95% CI 13.08,NR) and the OS rates at 1 year was 63.9% (95% CI 53.02, 73.00). Median DOR has not reached and the DOR and iDOR rates at 1 year were 80.64% and 87.39%, respectively. TRAEs occurred in 89.9% of the pts, with grade 3/4 AEs 31.9%, the followings were those incidences ≥1%, hyperglycemia (2.5%), elevated aspartate aminotransferase (1.7%), elevated serum bilirubin (1.7%), elevated serum creatine phosphokinase (1.7%), elevated lipase (1.7%), hypoalbuminemia (1.7%), hypokalemia (1.7%) and diabetic ketoacidosis (1.7%). Conclusions: HX008 shows its efficacy and safety in locally advanced or metastatic melanoma pts in the treatments of 2nd line or above. Randomized controlled studies are now on pending. Clinical trial information: NCT04749485.