Reference Detail

Ref Type

Journal Article

PMID

(33837053)

Authors

Zhang B, Huang J, Tang J, Hu S, Luo S, Luo Z, Zhou F, Tan S, Ying J, Chang Q, Zhang R, Geng C, Wu D, Gu X, Liu B

Title

Intratumoral OH2, an oncolytic herpes simplex virus 2, in patients with advanced solid tumors: a multicenter, phase I/II clinical trial.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal for immunotherapy of cancer	9	4	2021 Apr		J Immunother Cancer

URL

Abstract Text

OH2 is a genetically engineered oncolytic herpes simplex virus type 2 designed to selectively amplify in tumor cells and express granulocyte-macrophage colony-stimulating factor to enhance antitumor immune responses. We investigated the safety, tolerability and antitumor activity of OH2 as single agent or in combination with HX008, an anti-programmed cell death protein 1 antibody, in patients with advanced solid tumors.In this multicenter, phase I/II trial, we enrolled patients with standard treatment-refractory advanced solid tumors who have injectable lesions. In phase I, patients received intratumoral injection of OH2 at escalating doses (106, 107 and 108CCID50/mL) as single agent or with fixed-dose HX008. The recommended doses were then expanded in phase II. Primary endpoints were safety and tolerability defined by the maximum-tolerated dose and dose-limiting toxicities (DLTs) in phase I, and antitumor activity assessed per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) and immune-RECIST in phase II.Between April 17, 2019 and September 22, 2020, 54 patients with metastatic cancers were enrolled. Forty patients were treated with single agent OH2, and 14 with OH2 plus HX008. No DLTs were reported with single agent OH2 in phase I. Four patients, having metastatic mismatch repair-proficient rectal cancer or metastatic esophageal cancer, achieved immune-partial response, with two from the single agent cohort and two from the combination cohort. The duration of response were 11.25+ and 14.03+ months for the two responders treated with single agent OH2, and 1.38+ and 2.56+ months for the two responders in the combination cohort. The most common treatment-related adverse event (TRAE) with single agent OH2 was fever (n=18, 45.0%). All TRAEs were of grade 1-2, except one case of grade 3 fever in the 108CCID50/mL group. No treatment-related serious AEs occurred. Single agent OH2 induced alterations in the tumor microenvironment, with clear increases in CD3+ and CD8+ cell density and programmed death-ligand 1 expression in the patients' post-treatment biopsies relative to baseline.Intratumoral injection of OH2 was well-tolerated, and demonstrated durable antitumor activity in patients with metastatic esophageal and rectal cancer. Further clinical development of OH2 as single agent or with immune checkpoint inhibitors in selected tumor types is warranted.

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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

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

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	esophageal cancer	predicted - sensitive	OH2	Case Reports/Case Series	Actionable	In a Phase I/II trial, OH2 treatment in a CD274 (PD-L1)-positive (TPS=3) metastatic esophageal cancer patient led to an immune partial response 5.44 months after treatment initiation, followed by discontinuation of treatment, and an ongoing response lasting over 14.03 months (PMID: 33837053).	33837053
CD274 positive	rectum cancer	predicted - sensitive	OH2	Case Reports/Case Series	Actionable	In a Phase I/II trial, a patient with CD274 (PD-L1)-positive (TPS=3) metastatic rectal cancer treated with OH2 in a liver metastasis achieved a partial response with reduced size of the injected and non-injected liver lesions 6.89 months after treatment initiation and discontinued treatment but maintained an ongoing response lasting over 11.25 months (PMID: 33837053).	33837053