Puyouheng (pucotenlimab)

P2, N=36, Recruiting, Tongji Hospital

Pucotenlimab is an effective treatment option for previously treated advanced dMMR/MSI-H solid tumors, and the predictive value of KMT2D mutation warrants further research. This study is registered with ClinicalTrials.gov: NCT03704246.

P2, N=47, Not yet recruiting, Sun Yat-sen University

In AIR epigenetics, low ARID1A expression in TNBC contributed to AIR via the ARID1A/NPM1/PD-L1 axis, leading to poor outcome but sensitivity to ICI treatment.

Neutrophil count decreased (32.6%) was the most reported grade 3/4 TRAE. Conclusions Pucotenlimab combined with pemetrexed plus platinum demonstrated promising efficacy and safety for the 1st line nsq-NSCLC patients without EGFR/ALK mutations.

In CTR20191353, a phase 1b clinical trial of pucotenlimab combined with chemotherapy for TNBC, patients with ARID1A deficiency demonstrated significantly better prognosis and the longest progression-free survival was found in ARID1A-low/PD-L1-high group. In AIR epigenetics, TNBC ARID1A deficiency induced AIR via the ARID1A/NPM1/PD-L1 axis, leading to poor outcome. While ARID1A deficiency provided survival advantage for TNBC cells, it simultaneously left the Achilles' heel which could be targeted with ICI.

In the humanized mouse syngeneic A20 B-lymphoma (huCD47-A20) HuGEMM model, which has quadruple knocked-in hPD1xhPD-L1xhCD47xhSIRPα genes and an intact autologous immune-system, a contribution of effect is demonstrated for each targeted biologic (HX008 targeting PD1 and SIRPα-Fc targeting CD47), which is clearly augmented by the dual targeting with HX009. Lastly, the expression of the immune-checkpoints PD-L1/L2 and CD47 seemed co-regulated among a panel of lymphoma-derived-xenografts, where HX009 maybe more effective in those with upregulated CD47. Our data warrants HX009's further clinical development for treating NHLs.

Pucotenlimab as a ≥ 2 line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma.

P1/2, N=60, Recruiting, Binhui Biopharmaceutical Co., Ltd. | Trial completion date: Nov 2022 --> Nov 2023 | Trial primary completion date: Nov 2022 --> Nov 2023

P1/2, N=18, Recruiting, Shanghai Miracogen Inc.

P3, N=190, Not yet recruiting, Taizhou Hanzhong biomedical co. LTD

Pucotenlimab demonstrated durable antitumor activity and manageable safety for previously treated patients with advanced MSI-H/dMMR solid tumors. KMT2D gene mutation, along with NLR and TMB, warrants further investigation as predictive biomarkers. Clinical trial information: NCT03704246.

P3, N=350, Not yet recruiting, Taizhou Hanzhong biomedical co. LTD

In July 2022, pucotenlimab received conditional first approval in China for the treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumours, including patients with advanced colorectal cancer who have experienced disease progression after previous therapy with fluorouracil, oxaliplatin and irinotecan, as well as patients with other advanced solid tumours who have experienced disease progression after previous first-line therapy and have no satisfactory treatment alternatives. In September 2022, pucotenlimab was approved in China for the treatment of unresectable or metastatic melanomas after the failure of previous systemic therapy. This article summarizes the milestones in the development of pucotenlimab leading to the first approval for the treatment of MSI-H/dMMR advanced solid tumours.

P1/2, N=30, Recruiting, Shanghai Miracogen Inc. | Not yet recruiting --> Recruiting

There were no treatment-related deaths. Pucotenlimab plus GP demonstrated promising activity and a manageable safety profile in patients with mTNBC in the first-line setting.

P1/2, N=300, Recruiting, Wuhan Binhui Biotechnology Co., Ltd. | Trial completion date: Apr 2022 --> Apr 2023 | Trial primary completion date: Apr 2022 --> Apr 2023

P2, N=37, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Trial completion date: Apr 2022 --> Dec 2022 | Trial primary completion date: Feb 2022 --> Nov 2022

P1/2, N=30, Not yet recruiting, Shanghai Miracogen Inc.

HX008 plus GP demonstrated promising activity and manageable safety in patients with mTNBC in first-line setting. Exploring analysis of PAM50 subtype is being done.

P1/2, N=300, Recruiting, Wuhan Binhui Biotechnology Co., Ltd. | Trial completion date: Dec 2020 --> Apr 2022 | Trial primary completion date: Dec 2020 --> Apr 2022

HX008 as a ≥second-line therapy showed promising efficacy and a manageable safety profile in patients with MSI-H/dMMR advanced solid tumors.

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.

P2, N=123, Active, not recruiting, Taizhou Hanzhong biomedical co. LTD | Recruiting --> Active, not recruiting | Trial completion date: Mar 2020 --> Mar 2021

P1, N=63, Recruiting, Taizhou HoudeAoke Biomedical Co., Ltd.

P2, N=119, Active, not recruiting, Taizhou Hanzhong biomedical co. LTD

P2/3, N=700, Recruiting, Taizhou Hanzhong biomedical co. LTD

P1/2, N=31, Active, not recruiting, Taizhou Hanzhong biomedical co. LTD

P3, N=560, Recruiting, Taizhou Hanzhong biomedical co. LTD | Not yet recruiting --> Recruiting

P2, N=66, Not yet recruiting, Taizhou Hanzhong biomedical co. LTD

P1/2, N=300, Recruiting, Wuhan Binhui Biotechnology Co., Ltd. | Phase classification: P1 --> P1/2 | N=150 --> 300

P2, N=50, Not yet recruiting, Fudan University

P3, N=560, Not yet recruiting, Taizhou Hanzhong biomedical co. LTD

HX008 injection plus Irinotecan demonstrated promising activity and manageable safety in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine. Research Funding: None