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*Only for medical professionals to read for reference, 1 minute a day, to give you professional "talking information" in the tumor circle! (If you need the original text of the literature, you can add the editor WeChat yxj_oncology to obtain it) Key points CANCER DISCOV: a local mesothelin-targeted CAR-T cell therapy in patients with malignant pleural disease combined with anti-PD-1 drug pembrolizidine Anti-phase I trial Journal of Clinical Oncology: nab-Sirolimus for the treatment of malignant perivascular epithelioid cell tumors Phase II trial new drug: cyclophosphamide capsules to be included in the priority review frontier: this LAG-3 monoclonal antibody completed the first trial 01CANCER DISCOV: a phase I trial of local mesothelin-targeted CAR-T cell therapy combined with anti-PD-1 drug pembrolizumab in patients with malignant pleural disease, including metastatic lung cancer And breast cancer and malignant pleural mesothelioma (MPM) are aggressive solid tumors with poor response to treatment
.
For the first time, researchers have developed and conducted a phase I study of local delivery, autologous, mesothelin-targeted chimeric antigen receptor (CAR) T cell therapy
.
Screenshot of research publication In this study, intrapleural administration of 0.
3M to 60M CAR-T cells/kg in 27 patients (25 MPM patients) was safe and well tolerated
.
39% of patients had CAR-T cells detected in their peripheral blood for more than 100 days
.
Previous research data proved that PD-1 blockade can enhance the function of CAR-T cells in mice.
In this study, 18 patients with MPM also received pembrolizumab safely
.
In these patients, the median overall survival (OS) of CAR-T cell infusion was 23.
9 months
.
The disease of 8 patients was stable for ≥6 months; PET-CT scan of 2 patients showed complete metabolic remission
.
This study shows that the immune combination therapy strategy of CAR-T cells and PD-1 inhibitors should be further evaluated in solid tumor patients
.
02Journal of Clinical Oncology: Phase II trial of nab-Sirolimus in the treatment of malignant perivascular epithelioid cell tumor.
Malignant perivascular epithelioid cell tumor (PEComa) is a rare aggressive sarcoma, and there is no approved treatment
.
A few days ago, the Journal of Clinical Oncology published an online study on the safety and efficacy of the mammalian target of rapamycin inhibitor nab-Sirolimus in patients with malignant PEComa
.
Screenshot of study publication The study included patients with malignant PEComa who were injected intravenously with nab-Sirolimus 100mg/m2 once a week for 2 weeks and 3 weeks as a cycle
.
The primary endpoint is the objective response rate (ORR) evaluated by the independent radiology review board
.
Key secondary endpoints include duration of remission (DoR), progression-free survival (PFS), and safety
.
The results of the study showed that 34 patients with evaluable safety received treatment, and 31 patients with evaluable efficacy
.
ORR was 39% (95%CI: 22-58), 1 case had complete remission (CR) and 11 cases had partial remission (PR), 52% had stable disease (SD), and 10% had disease progression
.
The relief works quickly and lasting
.
After a median follow-up of 2.
5 years, the median DoR was not reached, and 7 of the 12 remission patients were receiving treatment
.
25/31 patients underwent tumor mutation profile analysis: 89% of patients with TSC2 mutation and 13% of patients without TSC2 mutation achieved confirmed remission (P<0.
001)
.
The median PFS was 10.
6 months (95%CI: 5.
5 months to not reached), and the median OS was 40.
8 months (95%CI: 22.
2 months to not reached)
.
Most treatment-related adverse events are grade 1 or 2 and can be managed through long-term treatment
.
No treatment-related adverse events ≥4 grade occurred
.
The results of this study indicate that nab-Sirolimus has shown good anti-tumor activity in patients with malignant PEComa, and it may become a new treatment option for patients with malignant PEComa
.
03 New drugs: Cyclophosphamide capsules are planned to be included in the priority review.
The latest announcement by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China shows that Hengrui Pharmaceuticals cyclophosphamide capsules are “new varieties and dosage forms of children’s drugs that meet the physiological characteristics of children”.
Harmony specifications are planned to be included in the priority review, and the proposed indications include malignant lymphoma, leukemia, breast cancer and other tumor types
.
Screenshot of CDE official website Cyclophosphamide (CTX) is one of the widely used anticancer drugs
.
According to reports in the literature, this is an inactive precursor cytotoxic drug that enters the body and is hydrolyzed by excess phosphoramidase or phosphatase in the liver or tumor, and turns into active phosphoramidite mustard.
Its mechanism It is cross-linked with DNA to inhibit DNA synthesis and interfere with the function of RNA, thereby inhibiting the proliferation of tumors and immune cells
.
The Hengrui Medicine cyclophosphamide capsule is planned to be included in the priority review.
The proposed indications include: (1) Malignant lymphoma (Ann Arbor stage III and IV), Hodgkin’s lymphoma, and lymphocytic lymphoma ( Nodular or diffuse), mixed cell lymphoma, histiocytic lymphoma, Burkitt lymphoma; (2) multiple myeloma; (3) leukemia: chronic lymphocytic leukemia, chronic myelogenous leukemia (Acute blast crisis is usually ineffective), acute myeloid and monocytic leukemia, acute lymphocytic (stem cell) leukemia (administration of cyclophosphamide during remission can effectively extend the remission period); (4) mycosis fungoides ( Advanced); (5) Neuroblastoma (diffuse disease); (6) Ovarian adenocarcinoma; (7) Retinoblastoma; (8) Breast cancer
.
04 Frontier: This LAG-3 monoclonal antibody completed the first subject administration On October 12, Henlius announced that its self-developed recombinant anti-LAG-3 humanized monoclonal antibody injection HLX26 will be used in entities The Phase I clinical study of tumor and lymphoma treatment was completed in China (excluding Hong Kong, Macao and Taiwan) for the first subject
.
LAG-3 is mainly expressed on activated T cells and some NK cells, and has a negative regulatory effect on the cell proliferation, activation and homeostasis of T cells
.
Inhibition of LAG-3 can reactivate T cells and restore the ability of T cells to kill tumor cells
.
HLX26 blocks the interaction between LAG-3 and its ligands, thereby blocking the LAG-3 mediated signal pathway that inhibits T cell function, and restoring the release of IL-2, IFN-γ and other cytokines from T cells.
The combination of anti-PD-1 monoclonal antibody injection HLX10 can block immune escape in the tumor microenvironment to achieve the purpose of suppressing tumors
.
Pre-clinical pharmacological studies, pharmacokinetic studies and safety evaluation have proved that HLX26 has anti-tumor effects in vivo and in vitro, and has good tolerability and safety
.
At the same time, HLX26 shows a more significant anti-tumor activity in combination with recombinant anti-PD-1 humanized monoclonal antibody injection HLX10, and has a synergistic effect
.
In April 2021, the clinical trial application of HLX26 for the treatment of solid tumors and lymphoma was approved by the National Medical Products Administration (NMPA) of China
.
References: [1]Adusumilli Prasad S,Zauderer Marjorie G,Riviere Isabelle et al.
A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab.
[J] .
Cancer Discov, 2021https://cancerdiscovery.
aacrjournals.
org/content/early/2021/10/09/2159-8290.
CD-21-0407[2]https://ascopubs.
org/doi /full/10.
1200/JCO.
21.
01728[3]https://mp.
weixin.
qq.
com/s/k3KH3ANh-841pN5-U_lGvw[4]https://mp.
weixin.
qq.
com/s/IPjutgBmG4HEvlVgt7qcNA
.
For the first time, researchers have developed and conducted a phase I study of local delivery, autologous, mesothelin-targeted chimeric antigen receptor (CAR) T cell therapy
.
Screenshot of research publication In this study, intrapleural administration of 0.
3M to 60M CAR-T cells/kg in 27 patients (25 MPM patients) was safe and well tolerated
.
39% of patients had CAR-T cells detected in their peripheral blood for more than 100 days
.
Previous research data proved that PD-1 blockade can enhance the function of CAR-T cells in mice.
In this study, 18 patients with MPM also received pembrolizumab safely
.
In these patients, the median overall survival (OS) of CAR-T cell infusion was 23.
9 months
.
The disease of 8 patients was stable for ≥6 months; PET-CT scan of 2 patients showed complete metabolic remission
.
This study shows that the immune combination therapy strategy of CAR-T cells and PD-1 inhibitors should be further evaluated in solid tumor patients
.
02Journal of Clinical Oncology: Phase II trial of nab-Sirolimus in the treatment of malignant perivascular epithelioid cell tumor.
Malignant perivascular epithelioid cell tumor (PEComa) is a rare aggressive sarcoma, and there is no approved treatment
.
A few days ago, the Journal of Clinical Oncology published an online study on the safety and efficacy of the mammalian target of rapamycin inhibitor nab-Sirolimus in patients with malignant PEComa
.
Screenshot of study publication The study included patients with malignant PEComa who were injected intravenously with nab-Sirolimus 100mg/m2 once a week for 2 weeks and 3 weeks as a cycle
.
The primary endpoint is the objective response rate (ORR) evaluated by the independent radiology review board
.
Key secondary endpoints include duration of remission (DoR), progression-free survival (PFS), and safety
.
The results of the study showed that 34 patients with evaluable safety received treatment, and 31 patients with evaluable efficacy
.
ORR was 39% (95%CI: 22-58), 1 case had complete remission (CR) and 11 cases had partial remission (PR), 52% had stable disease (SD), and 10% had disease progression
.
The relief works quickly and lasting
.
After a median follow-up of 2.
5 years, the median DoR was not reached, and 7 of the 12 remission patients were receiving treatment
.
25/31 patients underwent tumor mutation profile analysis: 89% of patients with TSC2 mutation and 13% of patients without TSC2 mutation achieved confirmed remission (P<0.
001)
.
The median PFS was 10.
6 months (95%CI: 5.
5 months to not reached), and the median OS was 40.
8 months (95%CI: 22.
2 months to not reached)
.
Most treatment-related adverse events are grade 1 or 2 and can be managed through long-term treatment
.
No treatment-related adverse events ≥4 grade occurred
.
The results of this study indicate that nab-Sirolimus has shown good anti-tumor activity in patients with malignant PEComa, and it may become a new treatment option for patients with malignant PEComa
.
03 New drugs: Cyclophosphamide capsules are planned to be included in the priority review.
The latest announcement by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China shows that Hengrui Pharmaceuticals cyclophosphamide capsules are “new varieties and dosage forms of children’s drugs that meet the physiological characteristics of children”.
Harmony specifications are planned to be included in the priority review, and the proposed indications include malignant lymphoma, leukemia, breast cancer and other tumor types
.
Screenshot of CDE official website Cyclophosphamide (CTX) is one of the widely used anticancer drugs
.
According to reports in the literature, this is an inactive precursor cytotoxic drug that enters the body and is hydrolyzed by excess phosphoramidase or phosphatase in the liver or tumor, and turns into active phosphoramidite mustard.
Its mechanism It is cross-linked with DNA to inhibit DNA synthesis and interfere with the function of RNA, thereby inhibiting the proliferation of tumors and immune cells
.
The Hengrui Medicine cyclophosphamide capsule is planned to be included in the priority review.
The proposed indications include: (1) Malignant lymphoma (Ann Arbor stage III and IV), Hodgkin’s lymphoma, and lymphocytic lymphoma ( Nodular or diffuse), mixed cell lymphoma, histiocytic lymphoma, Burkitt lymphoma; (2) multiple myeloma; (3) leukemia: chronic lymphocytic leukemia, chronic myelogenous leukemia (Acute blast crisis is usually ineffective), acute myeloid and monocytic leukemia, acute lymphocytic (stem cell) leukemia (administration of cyclophosphamide during remission can effectively extend the remission period); (4) mycosis fungoides ( Advanced); (5) Neuroblastoma (diffuse disease); (6) Ovarian adenocarcinoma; (7) Retinoblastoma; (8) Breast cancer
.
04 Frontier: This LAG-3 monoclonal antibody completed the first subject administration On October 12, Henlius announced that its self-developed recombinant anti-LAG-3 humanized monoclonal antibody injection HLX26 will be used in entities The Phase I clinical study of tumor and lymphoma treatment was completed in China (excluding Hong Kong, Macao and Taiwan) for the first subject
.
LAG-3 is mainly expressed on activated T cells and some NK cells, and has a negative regulatory effect on the cell proliferation, activation and homeostasis of T cells
.
Inhibition of LAG-3 can reactivate T cells and restore the ability of T cells to kill tumor cells
.
HLX26 blocks the interaction between LAG-3 and its ligands, thereby blocking the LAG-3 mediated signal pathway that inhibits T cell function, and restoring the release of IL-2, IFN-γ and other cytokines from T cells.
The combination of anti-PD-1 monoclonal antibody injection HLX10 can block immune escape in the tumor microenvironment to achieve the purpose of suppressing tumors
.
Pre-clinical pharmacological studies, pharmacokinetic studies and safety evaluation have proved that HLX26 has anti-tumor effects in vivo and in vitro, and has good tolerability and safety
.
At the same time, HLX26 shows a more significant anti-tumor activity in combination with recombinant anti-PD-1 humanized monoclonal antibody injection HLX10, and has a synergistic effect
.
In April 2021, the clinical trial application of HLX26 for the treatment of solid tumors and lymphoma was approved by the National Medical Products Administration (NMPA) of China
.
References: [1]Adusumilli Prasad S,Zauderer Marjorie G,Riviere Isabelle et al.
A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab.
[J] .
Cancer Discov, 2021https://cancerdiscovery.
aacrjournals.
org/content/early/2021/10/09/2159-8290.
CD-21-0407[2]https://ascopubs.
org/doi /full/10.
1200/JCO.
21.
01728[3]https://mp.
weixin.
qq.
com/s/k3KH3ANh-841pN5-U_lGvw[4]https://mp.
weixin.
qq.
com/s/IPjutgBmG4HEvlVgt7qcNA
