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DRUG:

Puyouheng (pucotenlimab)

i
Other names: HX008, HX 008, HX-008
Company:
HanX Biopharma, Lepu Med, Taizhou Hanzhong Biopharma
Drug class:
PD1 inhibitor
Related drugs:
1m
Preclinical pharmacology characterization of HX009, a novel PD1 x CD47 Bi-specific antibody. (PubMed, Sci Rep)
We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009's candidacy for its clinical development.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-1 (Programmed cell death 1) • TNFRSF4 (TNF Receptor Superfamily Member 4) • SIRPA (Signal Regulatory Protein Alpha)
|
TNFRSF4 expression
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Puyouheng (pucotenlimab) • HX-009
1m
New P2 trial
|
Puyouheng (pucotenlimab)
2ms
Clinical predictive value of PD-1/PD-L1-induced electrocardiogram changes for cardiotoxicity (PubMed, Zhonghua Zhong Liu Za Zhi)
Groups were divided according to immunotherapy regimen: Group A (drug code: 609A), 16 patients were given 1 mg/kg of the drug for 21 days; Group B (drug code: HX008), 23 patients were treated with 200mg for 21 days; Group C (drug code: GB226), 28 patients were treated with 3mg/kg for 14 days; Group D (drug code: LP002), 26 patients were treated with 900mg for 14 days. The high sensitivity of early ECG changes induced by immune checkpoint inhibitors enables early prediction of related cardiotoxicity. The presence or absence of comorbid underlying disease and drug dosage are correlated with the occurrence of adverse cardiac events, and these early changes provide a evidence for clinical treatment and prevention.
Journal
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1)
|
Puyouheng (pucotenlimab) • Aibining (geptanolimab)
2ms
CCGLC-013: Combined HAIC, Lenvatinib and Pucotenlimab As Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma (clinicaltrials.gov)
P2, N=36, Recruiting, Tongji Hospital | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Dec 2025 --> Dec 2026
Trial completion date • Trial primary completion date
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Lenvima (lenvatinib) • oxaliplatin • Puyouheng (pucotenlimab)
3ms
Trial completion • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
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HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • PTEN mutation + HR positive • CHEK1 expression • HER-2 negative + HR positive + BRCA mutation
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Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
4ms
Clinical Efficacy Study of Pucotenlimab Combined With Neoadjuvant Chemotherapy in Advanced Endometrial Cancer (clinicaltrials.gov)
P2, N=39, Not yet recruiting, Women's Hospital School Of Medicine Zhejiang University
New P2 trial • Metastases
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carboplatin • paclitaxel • Puyouheng (pucotenlimab)
5ms
New P2 trial
|
Lenvima (lenvatinib) • Puyouheng (pucotenlimab)
5ms
New P4 trial
|
BRAF (B-raf proto-oncogene) • RAS (Rat Sarcoma Virus)
|
Avastin (bevacizumab) • Puyouheng (pucotenlimab)
6ms
Trial initiation date
|
Lenvima (lenvatinib) • oxaliplatin • Puyouheng (pucotenlimab)
6ms
New P1/2 trial
|
Puyouheng (pucotenlimab)
12ms
New P2 trial
|
Lenvima (lenvatinib) • doxorubicin hydrochloride • Puyouheng (pucotenlimab)
1year
Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A multicenter phase 2 study. (PubMed, Cell Rep Med)
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 data • Journal • Mismatch repair • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
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MSI (Microsatellite instability) • KMT2D (Lysine Methyltransferase 2D)
|
MSI-H/dMMR • KMT2D mutation
|
Puyouheng (pucotenlimab)
1year
New P2 trial
|
Lenvima (lenvatinib) • Puyouheng (pucotenlimab)
1year
Low level of ARID1A contributes to adaptive immune resistance and sensitizes triple-negative breast cancer to immune checkpoint inhibitors. (PubMed, Cancer Commun (Lond))
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.
Retrospective data • Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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NPM1 (Nucleophosmin 1) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8)
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PD-L1 expression • NPM1 expression
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Tecentriq (atezolizumab) • Puyouheng (pucotenlimab)
over1year
Pucotenlimab (HX008) - humanized anti-PD-1 monoclonal antibody plus pemetrexed and platinum as first-line treatment for advanced non-squamous non-small-cell lung cancer (nsqNSCLC): A single-arm multicenter phase II study (ESMO 2023)
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.
Clinical • P2 data • PD(L)-1 Biomarker • IO biomarker • Metastases
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
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ALK mutation
|
pemetrexed • Puyouheng (pucotenlimab)
over1year
ARID1A deficiency in triple-negative breast cancer induces adaptive immune resistance and sensitivity to immune checkpoint inhibitors. (ASCO 2023)
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.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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NPM1 (Nucleophosmin 1) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8)
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PD-L1 expression • PD-L1-L
|
Puyouheng (pucotenlimab)
over1year
HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models. (PubMed, Sci Rep)
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.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-1 (Programmed cell death 1) • SIRPA (Signal Regulatory Protein Alpha)
|
Puyouheng (pucotenlimab) • HX-009
almost2years
Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study. (PubMed, BMC Cancer)
Pucotenlimab as a ≥ 2 line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma.
P2 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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TNFA (Tumor Necrosis Factor-Alpha) • PD-L2 (Programmed Cell Death 1 Ligand 2) • CCL11 (C-C Motif Chemokine Ligand 11) • CCL2 (Chemokine (C-C motif) ligand 2)
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Puyouheng (pucotenlimab)
almost2years
OH2 Injection in Combination With HX008 for Melanoma. (clinicaltrials.gov)
P1/2, N=60, Recruiting, Binhui Biopharmaceutical Co., Ltd. | Trial completion date: Nov 2022 --> Nov 2023 | Trial primary completion date: Nov 2022 --> Nov 2023
Trial completion date • Trial primary completion date • Combination therapy
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
PD-L1 expression
|
Puyouheng (pucotenlimab) • BS001
almost2years
New P1/2 trial • Combination therapy • Metastases
|
EGFR (Epidermal growth factor receptor)
|
EGFR positive
|
Puyouheng (pucotenlimab) • MRG003
2years
New P3 trial • Mismatch repair • Metastases
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MSI (Microsatellite instability)
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MSI-H/dMMR
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Avastin (bevacizumab) • Erbitux (cetuximab) • 5-fluorouracil • oxaliplatin • irinotecan • Puyouheng (pucotenlimab)
2years
Clinical efficacy and biomarker analysis of pucotenlimab (HX008) in patients with previously treated advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A single-arm, multicenter, phase 2 study. (ASCO-GI 2023)
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.
Clinical • P2 data • Mismatch repair • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • KMT2D (Lysine Methyltransferase 2D)
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PD-L1 expression • MSI-H/dMMR • KMT2D mutation • MSI-H/dMMR + KMT2D mutation
|
Puyouheng (pucotenlimab)
2years
New P3 trial • Metastases
|
BRAF (B-raf proto-oncogene)
|
BRAF mutation • BRAF V600
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Keytruda (pembrolizumab) • cisplatin • temozolomide • Puyouheng (pucotenlimab)
2years
Pucotenlimab: First Approval. (PubMed, Drugs)
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.
Review • Journal
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MSI (Microsatellite instability) • PD-L2 (Programmed Cell Death 1 Ligand 2)
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MSI-H/dMMR
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5-fluorouracil • oxaliplatin • irinotecan • Puyouheng (pucotenlimab)
over2years
A Study of MRG002 in the Treatment of Patients With HER2-expressed Advanced Malignant Solid Tumors. (clinicaltrials.gov)
P1/2, N=30, Recruiting, Shanghai Miracogen Inc. | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
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HER-2 expression
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Puyouheng (pucotenlimab) • trastuzumab vedotin (MRG002)
over2years
Phase 1b clinical trial of pucotenlimab (HX008), a novel anti-PD-1 monoclonal antibody, combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer. (PubMed, Front Oncol)
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 data • Journal
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PD-L1 (Programmed death ligand 1) • PD-L2 (Programmed Cell Death 1 Ligand 2)
|
cisplatin • gemcitabine • Puyouheng (pucotenlimab)
over2years
OH2 Oncolytic Viral Therapy in Solid Tumors (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Oncolytic virus
|
CSF2 (Colony stimulating factor 2)
|
irinotecan • Puyouheng (pucotenlimab) • BS001
over2years
CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)
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
Enrollment open • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • CHEK1 expression
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Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
over2years
New P1/2 trial • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
Puyouheng (pucotenlimab) • trastuzumab vedotin (MRG002)
3years
UPDATE SURVIVAL OF PHASE 1B CLINICAL TRIAL OF HX008, A NOVEL ANTI-PD-1 MONOCLONAL ANTIBODY, COMBINED WITH GEMCITABINE AND CISPLATIN IN THE FIRST-LINE TREATMENT OF METASTATIC TRIPLE-NEGATIVE BREAST CANCER (ABC6 2021)
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 data • Clinical
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Prosigna™ Breast Cancer Prognostic Gene Signature Assay
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cisplatin • gemcitabine • Puyouheng (pucotenlimab)
over3years
OH2 Oncolytic Viral Therapy in Solid Tumors (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Oncolytic virus
|
CSF2 (Colony stimulating factor 2)
|
irinotecan • Puyouheng (pucotenlimab) • BS001
over3years
[VIRTUAL] Efficacy of HX008 in high microsatellite instability/mismatch repair–defificient (MSI-H/dMMR) solid tumors: Results from a multicenter phase II open-label study. (ASCO 2021)
HX008 as a ≥second-line therapy showed promising efficacy and a manageable safety profile in patients with MSI-H/dMMR advanced solid tumors.
Clinical • P2 data • Mismatch repair • Microsatellite instability
|
MSI (Microsatellite instability)
|
MSI-H/dMMR
|
Puyouheng (pucotenlimab)
over3years
Intratumoral OH2, an oncolytic herpes simplex virus 2, in patients with advanced solid tumors: a multicenter, phase I/II clinical trial. (PubMed, J Immunother Cancer)
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.
Clinical • P1/2 data • Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8)
|
PD-L1 expression
|
Puyouheng (pucotenlimab)
almost4years
Recombinant Human Anti-PD-1 Monoclonal Antibody HX008 Injection for the Treatment of Advanced Solid Tumors (clinicaltrials.gov)
P2, N=123, Active, not recruiting, Taizhou Hanzhong biomedical co. LTD | Recruiting --> Active, not recruiting | Trial completion date: Mar 2020 --> Mar 2021
Clinical • Enrollment closed • Trial completion date
|
MSI (Microsatellite instability)
|
MSI-H/dMMR
|
Puyouheng (pucotenlimab)
almost4years
Clinical • New P1 trial
|
PD-L1 (Programmed death ligand 1)
|
Puyouheng (pucotenlimab) • LP002
almost4years
HX008-II-MM-01: A Study of HX008 for the Treatment of Patients With Malignant Melanoma (clinicaltrials.gov)
P2, N=119, Active, not recruiting, Taizhou Hanzhong biomedical co. LTD
Clinical • New P2 trial
|
IFNG (Interferon, gamma)
|
Puyouheng (pucotenlimab)
almost4years
Clinical • New P2/3 trial
|
EGFR (Epidermal growth factor receptor)
|
Keytruda (pembrolizumab) • cisplatin • carboplatin • pemetrexed • Puyouheng (pucotenlimab)
almost4years
Clinical • New P1/2 trial
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
HER-2 negative • PGR negative
|
cisplatin • gemcitabine • Puyouheng (pucotenlimab)
4years
HX008 Plus Irinotecan Versus Placebo Plus Irinotecan as Second-line Treatment in Advanced Gastric Cancer (clinicaltrials.gov)
P3, N=560, Recruiting, Taizhou Hanzhong biomedical co. LTD | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
PD-L1 (Programmed death ligand 1)
|
irinotecan • Puyouheng (pucotenlimab)
4years
Study of HX008 for the Treatment of Anaplastic Thyroid Cancer (ATC) (clinicaltrials.gov)
P2, N=66, Not yet recruiting, Taizhou Hanzhong biomedical co. LTD
Clinical • New P2 trial
|
PD-L1 (Programmed death ligand 1)
|
Puyouheng (pucotenlimab)
over4years
OH2 Oncolytic Viral Therapy in Solid Tumors (clinicaltrials.gov)
P1/2, N=300, Recruiting, Wuhan Binhui Biotechnology Co., Ltd. | Phase classification: P1 --> P1/2 | N=150 --> 300
Phase classification • Enrollment change • Oncolytic virus
|
CSF2 (Colony stimulating factor 2)
|
irinotecan • Puyouheng (pucotenlimab) • BS001
over4years
Clinical • New P2 trial • BRCA Biomarker • PARP Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCC (FA Complementation Group C)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • CHEK1 expression
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Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)