Reference Detail

Ref Type

Journal Article

PMID

(32321714)

Authors

Tang B, Chi Z, Chen Y, Liu X, Wu D, Chen J, Song X, Wang W, Dong L, Song H, Wu H, Feng H, Yao S, Qin S, Zhang X, Guo J

Title

Safety, Efficacy, and Biomarker Analysis of Toripalimab in Previously Treated Advanced Melanoma: Results of the POLARIS-01 Multicenter Phase II Trial.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	26	16	2020 Aug 15	4250-4259	Clin Cancer Res

URL

Abstract Text

In contrast to the predominant chronic UV exposure-induced cutaneous melanoma in Caucasians, acral and mucosal comprise the majority of melanomas in Asia and respond less effectively to established treatments. The clinical application of PD-1 blockade is yet to be explored in metastatic melanoma in China.This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese patients with melanoma who had failed in systemic treatments. Toripalimab was given at 3 mg/kg i.v. once every 2 weeks until disease progression or unacceptable toxicity. The primary objective was safety and objective response rate.128 Patients with melanoma were enrolled, including 50 acral and 22 mucosal. As of August 15, 2019, 23 months after the last enrollment, 116 (90.6%) experienced treatment-related adverse events. ≥Grade 3 TRAEs occurred in 25 (19.5%) patients. Among 127 patients assessed, 1 complete response, 21 partial response, and 51 stable disease were observed for objective response rate of 17.3% and disease control rate of 57.5%. Median duration of response was not reached. Median progression-free survival was 3.6 months [95% confidence interval (CI) 2.7-5.3] and median overall survival was 22.2 months (95% CI, 15.3-NE). Patients with positive PD-L1 staining in tumor biopsies had significant better ORR (38.5% vs. 11.9%, P = 0.0065), PFS (7.7 months vs. 2.7 months, P = 0.013), and OS (not reached vs. 14.4 months, P = 0.0005) than PD-L1-negative patients.This is the largest prospective anti-PD-1 clinical study in advanced melanoma with predominantly acral and mucosal subtypes. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma refractory to standard therapy.See related commentary by Shoushtari et al., p. 4171.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Toripalimab-tpzi	Toripalimab-tpzi	9	2

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Toripalimab-tpzi	Loqtorz	Toripalimab\|JS001\|JS-001\|TAB001	Immune Checkpoint Inhibitor 149 PD-L1/PD-1 antibody 122	Loqtorz (toripalimab-tpzi) is a monoclonal antibody that targets PD-1 (PDCD1) and inhibits binding of the PD-L1 (CD274) ligand, potentially resulting in enhanced anti-tumor immune response and decreased tumor growth (PMID: 28317872; PMID: 32277740, PMID: 32406293, PMID: 32321714). Loqtorz (toripalimab-tpzi) in combination with cisplatin and gemcitabine is FDA-approved for use in adult patients with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (FDA.gov).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	melanoma	predicted - sensitive	Toripalimab-tpzi	Phase II	Actionable	In a Phase II trial (POLARIS-01), Loqtorz (toripalimab-tpzi) resulted in a more favorable objective response rate (38.5% vs 11.9%, p=0.0065), disease control rate (80.8% vs 48.8%, p=0.006), progression-free survival (7.7 vs 2.7 mo, HR=0.53, p=0.013), and overall survival (not reached vs 14.4 mo, HR=0.35, p=0.0005) in patients with CD274 (PD-L1)-positive advanced melanoma (n=26) compared to patients with CD274 (PD-L1)-negative (n=84) tumors (PMID: 32321714; NCT03013101).	32321714