Ignite Creation Date:
2024-06-16 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06429397
Status:
RECRUITING
Last Update Posted:
2024-05-28
First Post:
2024-04-08
Brief Title:
First-line Anlotinib Combined With Penpulimab for Advanced Pheochromocytoma A Single-arm Multicenter Prospective Phase II Study
Sponsor:
Sun Yat-sen University
Organization:
Sun Yat-sen University
Study Overview
Official Title:
A Single-arm Multicenter Prospective Phase II Clinical Study of Anlotinib Combined With Penpulimab in the First-line Treatment of Advanced PheochromocytomaParaganglioma
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
There is currently no standard first-line treatment for stage PPGL and the 5-year survival rate of patients with advanced pheochromocytomaparaganglioma PPGL is low ranging from 30 to 60 At present several domestic teams have carried out clinical studies on the treatment of advanced PPGL with good efficacy In the early stage our center used anrotinib to treat advanced PPGL and the overall effective rate reached 44 In the early stage our team used anrotinib combined with PD-1 monoclonal antibody to treat advanced PPGL patients The effective rate reached 66 23 Therefore the investigators plan to further conduct prospective studies to explore the efficacy and safety of anlotinib combined with PD-1 monoclonal antibody in the treatment of advanced PPGL so as to bring benefits to patients with advanced PPGL
Detailed Description:
11 Adrenal pheochromocytomaparaganglioma pheochromocytoma PCC and Paraganglioma PGL pheochromocytoma and paraganglioma PPGL are rare malignant tumors with neuroendocrine function and metastatic potential The incidence is 04-21 personsmillion 80-85 originate from the adrenal medulla and 15-20 originate from the neural crest tissue from the neck to the pelvis The PPGL metastasis rate at initial diagnosis is 10 and the risk of metastasis is as high as 34-69 for those with SDHB gene mutations The recurrence rate of PPGL patients after radical resection was 30 47 recurred with multiple nodules 58 with metastasis The most common sites of metastasis were lymph nodes and bone 70-80 followed by lung and liver 50 In addition some PPGL is difficultunresectable due to its proximity to important structures such as large blood vessels or nerves and the 5-year survival rate for advanced PPGL is 30-60
Early PPGL can be cured by surgery but late PPGL is mainly systemic therapy such as chemotherapy targeted drugs and nuclide therapy The main chemotherapy regimen for advanced PPGL is cyclophosphamide - vincristine - dacarbazine CVD regimen and ESMO guidelines recommend CVD for patients with rapid tumor progression and heavy tumor burden The objective response rate of CVD regimen was 33 the median duration of response was 13 years and the 5-year survival rate of patients with effective CVD was 51 The main limitations of CVD in the treatment of advanced PPGL are 1 The average number of cycles required for CVD chemotherapy is 116108 months 2 The incidence of CVD related toxicity such as bone marrow suppression and neurotoxicity was 50 Some patients could not maintain treatment due to intolerance and long-term use of the above drugs could increase the incidence of hematological tumors which may be related to the alkylating properties of daparbazine
Domestic guidelines and the FDA recommend 131I-MIBG for the treatment of advanced PPGL Loh et al reviewed and analyzed 21 central LSA-131I-MIBG clinical studies 30 patients could have Partial Response PR Gonias S et al Phase II clinical study of HSA-131I-MIBG in the treatment of advanced PPGL 22 of patients could have PR Two 131I-MIBGs show good efficacy but there are no phase III clinical studies to further validate efficacy and safety Limitations of radionuclide therapy lie in 1 the narrow range of indications 1 ESMO guidelines indicate that only 50 of patients with positive MIBG scan are suitable ② Pregnant women and pregnant patients should not use 2 Severe hematological toxicity the incidence of myosuppression was 4-79 about 40 of patients treated with low-dose 131I-MIBG had grade 34 toxicity while those treated with high-dose 131I-MIBG had up to 80 of which 25 needed hematological therapy and secondary hematological tumors could be developed 3 Hypogonadism In addition at present the units that can carry out nuclide therapy in China are limited and patients can not perform nuclide therapy again after receiving progress of nuclide therapy
12 Tyrosine kinase inhibitors TKI and advanced adrenal pheochromocytomaparaganglioma Tyrosine kinase TK is a key site in the activation and regulation of cell proliferation signaling pathways Abnormal TK pathway caused by mutation translocation or amplification can lead to tumor occurrence progression invasion and metastasis Tyrosine kinase inhibitors TKI mainly act on vascular endothelial growth factor receptor VEGFR platelet growth factor PDGFR and insulin family receptor InsR TKI acts on advanced PPGL through the pseudo-hypoxia pathway and VEGF angiogenesis pathway
Advanced PPGL with abundant blood supply and high expression of angiogenic factor VEGF can promote tumor neovascularization and provide oxygen and nutrition for tumors TKI has a good therapeutic effect on advanced PPGL with high VEGF expression which may be related to its blocking of VEGF signaling pathway continuous inhibition of tumor neovascugenesis and promotion of abnormal blood vessel normalization In addition HIF axis misalignment can also promote the development and transfer of PPGL SDH gene mutations are the most common in PPGL including SDHA SDHB SDHC SDHD which cause abnormalities in the subunit encoding the succinate dehydrogenase complex SDH and block the tricarboxylic acid cycle TCA Abnormal TCA can inhibit hypoxia-inducing factor HIF-α proline hydroxylase and HIF-α accumulation will activate the pseudo-hypoxia pathway and up-regulate the expression of VEGF and other factors
ESMO guidelines recommend sunitinib for the treatment of advanced PPGL Currently the only prospective phase II clinical study showed that 3 cases 13 had PR SDHB SDHD RET gene mutations respectively A retrospective study of 17 cases of advanced PPGL treated by MD Anderson and Gustavvy-Roussy et al showed that there were 3 cases of PR and 5 cases of SD 6 of which were SDHB or VHL gene mutations In the study grade 1-2 toxicity was the most common with about 68 of patients presenting symptoms such as fatigue nausea and vomiting palm-plantar dyspepsia etc while only 5612 of patients presented 34 toxicity mainly manifested as nausea vomiting and hypertension without hematological toxicity
Retrospective studies have also shown that Renvastinib pazopanib acitinib and other TKI have certain efficacy in advanced PPGL but there is a lack of prospective clinical evidence Hassan Nelson L et al treated 11 cases of advanced PPGL with lenvatinib and the results were 5 cases PR 3 cases SD and the median PFS was 147 months Mauricio Emmanuel Burotto Pichun et al are conducting a study on the treatment of 11 cases of advanced PPGL with acitinib 4 cases of PR and 6 cases of SD The above studies show the preliminary efficacy of various TKI and the effect may be better for SDHB mutations with a controllable safety mainly hypertension In 2017 preliminary results of a prospective clinical study of cabotinib in the treatment of advanced PPGL were reported in the conference abstract ORR of 45 PFS of 11 months and no grade 34 toxicity In summary TKI monotherapy in the treatment of advanced PPGL shows some effect but it is still not satisfactory
There is currently no standard first-line treatment for advanced PPGL NCCN guidelines and Chinas expert consensus 2020 edition recommend the use of tumor reduction surgery palliative resection combined with radiotherapy radionuclide therapy or systemic chemotherapy and other treatment options but the above methods have uncertain efficacy and certain limitations still need to be confirmed by prospective experiments so patients are recommended to participate in clinical trials
13 Application of antirotinib hydrochloride in advanced adrenal pheochromocytomaparaganglioma Allotinib AL3818 is manufactured by Zhengda Tianqing Pharmaceutical Group Co LTD CTTQ Lianyungang Jiangsu China self-developed TKI drugs targeting VEGFR1-3 FGFR1-4 PDGFRα G β rearrangement RET and stem cell factor receptor c-Kit during transfection 26 Anlotinib has shown good anticancer activity in vitroin vitro 27 A multicentre randomized controlled Phase II clinical study of anlotinib in first-line treatment of metastatic renal cell carcinoma mRCC NCT0207203128 showed similar efficacy of anlotinib and Sunitinib There were no significant differences in median PFS 17May vs 16June P 005 OS ORR and DCR P 005 but the toxicity of anrotinib was lower and the incidence of 34 toxicity was significantly lower than that of Sunitinib 289 vs558 P 001 The main symptoms were hypertension and hand-foot syndrome and no hematological toxicity was found In addition Lin J et al also confirmed that anlotinib and Sunitinib had similar efficacy but higher safety TKI treatment of advanced PPGL has a similar mechanism of action but anlotinib safety may be better In addition our team has a certain foundation in the study of anrotinib in the treatment of advanced PPGL In the early stage anrotinib monotherapy was used to treat advanced PPGL in 4 cases and PR in 2 cases 1 case was a SHDB mutation and the adverse reactions were mostly grade 1-2 with hypertension and hand-foot syndrome as the main manifestations Therefore antirotinib may have better efficacy and safety in advanced PPGL which is worthy of further clinical exploration
14 Application of peamprizumab in advanced adrenal pheochromocytomaparaganglioma PD-1PD-L1 monoclonal antibody kills tumors by activating its own normal anti-tumor immune mechanism In 2014 Pembrolizumab achieved results in melanoma officially ushering in the era of global immunotherapy Subsequently indications and significant curative effects were also obtained in multi-tumor species such as non-small cell lung cancer gastric cancer and kidney cancer
PD-L1 is mainly expressed in tumor cells and antigen-presenting cells APCs and is closely related to tumor immune escape 33 PD-L1 receptor of tumor cell membrane binds to PD-1 receptor of T cell membrane which weakens the ability of cytotoxic T lymphocytes to kill tumor cells PD-1PD-L1 mab blocks the above signaling process and restoresactivates the anti-tumor activity of T cells
A study in Peking Union Medical College Hospital 35 showed that 597 were positive for PPGL PD-L1 expression HIS10 and the positive rate of PD-L1 in advanced PPGL was 10011 Study 36 showed that PD-L1 expression was positive in 4 out of 10 advanced PPGL cases 40 Studies indicated that the cytotoxic T lymphocyte infiltration level was increased in advanced PPGL P0092 Therefore PD-1 monoclonal antibody may have some significance in the treatment of advanced PPGL At present only A few cases have been reported in the treatment of advanced PPGL with PD-1 monoclonal antibody The Phase II clinical study conducted by Naing A et al in the treatment of advanced PPGL patients with pembrolizumab showed that 43 4 cases had no progress at 27 weeks 675 months This suggests that PD-1 monoclonal antibody has a certain effect in the treatment of advanced PPGL but PD-1 monotherapy can not meet the clinical needs
KATO Y et al proposed that the effective rate of PD-1 monoclonal antibody in the single treatment of solid tumors was 20-30 and the therapeutic effect was not satisfactory The study of PD-1 monoclonal antibody combined with TKI in the treatment of liver cancer suggests that the combination of PD-1 monoclonal antibody can reverse the immunosuppressor tumor microenvironment in which PD-1 monoclonal antibody is ineffective and assist PD-1PD-L1 monoclonal antibody to activate cytotoxic T lymphocytes The efficacy of acitinib combined with PD-1 mab in the second-line treatment of patients with metastatic renal cancer was significantly higher than that of acitinib ORR 336 vs 201 P0015 PFS 117 months vs 75 months P0002
Piamprilizumab Anicol is a new PD-1 monoclonal antibody developed by Zhengda Tianqing Pharmaceutical Group Co LTD which has been approved for Hodgkins lymphoma RR cHL and squamous non-small cell lung cancer NSCLC indications in China Pembrolizumab has achieved significant efficacy in the treatment of classic Hodgkin lymphoma metastatic nasopharyngeal carcinoma gastricesophageal junction adenocarcinoma and other tumor species in clinical studies with ORR of 894 297 and 263 respectively
Anicol is a humanized IgG1 subtype of PD-1 monoclonal antibody that eliminates Fc effects The IgG1 subtype reduces immune escape by eliminating antibody-dependent cell-mediated cytotoxicity ADCC antibody-dependent cell-mediated phagocytosis ADCP and complement-dependent cytotoxicity CDC The combination of anil with FcR can reduce the occurrence of adverse immune reactions and the incidence of grade 3 and above toxicities such as immune-associated pneumonia hepatitis myocardium and pancreatitis is lower than that of sindillizumab tirellizumab and triplizumab Therefore this study intends to use anicol combined with anlotinib to explore its efficacy and safety in advanced PPGL
15 Application of antirotinib combined with PD-1 monoclonal antibody in advanced pheochromocytomaparaganglioma The combination of TKI and PD-1 monoclonal antibody is a research hotspot in the treatment of advanced tumors Target-free therapy has been widely used in renal urothelial lung liver and other tumors and has achieved remarkable efficacy 46
Only a few cases of combined treatment for advanced PPGL have been reported at home and abroad In Taizhou Hospital of Zhejiang Province in 2022 a patient was treated with palizumab injection 200 mgonce every 3 weeks for intravenous immunotherapy combined with anrotinib 10 mg orally once a day 14 days and 7 days every 3 weeks for a course of treatment The left adrenal mass 96cm 84cm and the multiple intrahepatic mass up to 93cm 88cm were both reduced In the early stage our team used anrotinib combined with PD-1 monoclonal antibody to treat 3 patients and the efficacy reached PR 66 23 including 1 case with SHDB mutation This suggests that targeted immunotherapy for advanced PPGL may have better efficacy
In an open multicenter phase IbII clinical study of anlotinib combined with piamprizumab in the treatment of advanced hepatocellular carcinoma the ORR was 31 and the DCR was 828 The median PFS was 88 months 95 CI 40-123 months 80 were grade 12 toxicity such as elevated AST elevated ALT elevated blood bilirubin etc Only 194 had grade 34 toxicity such as hypertension and rash This is an improvement in efficacy and a decrease in toxicity compared to the treatment of advanced hepatocellular carcinoma with altilizumab combined with bevacizumab or carrilizumab combined with apatinib
At present there have been no studies on the combination of targeted drugs and immunodrugs in the treatment of advanced PPGL at home and abroad Therefore this study will for the first time apply the combination of TKI drugs antirotinib and PD-1 monoclonal antibody Pembrolizumab to metastaticunresectable pheochromocytomaparaganglioma so as to explore the efficacy and safety of combined drugs in the treatment of advanced pheochromocytomaparaganglioma
Early PPGL can be cured by surgery but late PPGL is mainly systemic therapy such as chemotherapy targeted drugs and nuclide therapy The main chemotherapy regimen for advanced PPGL is cyclophosphamide - vincristine - dacarbazine CVD regimen and ESMO guidelines recommend CVD for patients with rapid tumor progression and heavy tumor burden The objective response rate of CVD regimen was 33 the median duration of response was 13 years and the 5-year survival rate of patients with effective CVD was 51 The main limitations of CVD in the treatment of advanced PPGL are 1 The average number of cycles required for CVD chemotherapy is 116108 months 2 The incidence of CVD related toxicity such as bone marrow suppression and neurotoxicity was 50 Some patients could not maintain treatment due to intolerance and long-term use of the above drugs could increase the incidence of hematological tumors which may be related to the alkylating properties of daparbazine
Domestic guidelines and the FDA recommend 131I-MIBG for the treatment of advanced PPGL Loh et al reviewed and analyzed 21 central LSA-131I-MIBG clinical studies 30 patients could have Partial Response PR Gonias S et al Phase II clinical study of HSA-131I-MIBG in the treatment of advanced PPGL 22 of patients could have PR Two 131I-MIBGs show good efficacy but there are no phase III clinical studies to further validate efficacy and safety Limitations of radionuclide therapy lie in 1 the narrow range of indications 1 ESMO guidelines indicate that only 50 of patients with positive MIBG scan are suitable ② Pregnant women and pregnant patients should not use 2 Severe hematological toxicity the incidence of myosuppression was 4-79 about 40 of patients treated with low-dose 131I-MIBG had grade 34 toxicity while those treated with high-dose 131I-MIBG had up to 80 of which 25 needed hematological therapy and secondary hematological tumors could be developed 3 Hypogonadism In addition at present the units that can carry out nuclide therapy in China are limited and patients can not perform nuclide therapy again after receiving progress of nuclide therapy
12 Tyrosine kinase inhibitors TKI and advanced adrenal pheochromocytomaparaganglioma Tyrosine kinase TK is a key site in the activation and regulation of cell proliferation signaling pathways Abnormal TK pathway caused by mutation translocation or amplification can lead to tumor occurrence progression invasion and metastasis Tyrosine kinase inhibitors TKI mainly act on vascular endothelial growth factor receptor VEGFR platelet growth factor PDGFR and insulin family receptor InsR TKI acts on advanced PPGL through the pseudo-hypoxia pathway and VEGF angiogenesis pathway
Advanced PPGL with abundant blood supply and high expression of angiogenic factor VEGF can promote tumor neovascularization and provide oxygen and nutrition for tumors TKI has a good therapeutic effect on advanced PPGL with high VEGF expression which may be related to its blocking of VEGF signaling pathway continuous inhibition of tumor neovascugenesis and promotion of abnormal blood vessel normalization In addition HIF axis misalignment can also promote the development and transfer of PPGL SDH gene mutations are the most common in PPGL including SDHA SDHB SDHC SDHD which cause abnormalities in the subunit encoding the succinate dehydrogenase complex SDH and block the tricarboxylic acid cycle TCA Abnormal TCA can inhibit hypoxia-inducing factor HIF-α proline hydroxylase and HIF-α accumulation will activate the pseudo-hypoxia pathway and up-regulate the expression of VEGF and other factors
ESMO guidelines recommend sunitinib for the treatment of advanced PPGL Currently the only prospective phase II clinical study showed that 3 cases 13 had PR SDHB SDHD RET gene mutations respectively A retrospective study of 17 cases of advanced PPGL treated by MD Anderson and Gustavvy-Roussy et al showed that there were 3 cases of PR and 5 cases of SD 6 of which were SDHB or VHL gene mutations In the study grade 1-2 toxicity was the most common with about 68 of patients presenting symptoms such as fatigue nausea and vomiting palm-plantar dyspepsia etc while only 5612 of patients presented 34 toxicity mainly manifested as nausea vomiting and hypertension without hematological toxicity
Retrospective studies have also shown that Renvastinib pazopanib acitinib and other TKI have certain efficacy in advanced PPGL but there is a lack of prospective clinical evidence Hassan Nelson L et al treated 11 cases of advanced PPGL with lenvatinib and the results were 5 cases PR 3 cases SD and the median PFS was 147 months Mauricio Emmanuel Burotto Pichun et al are conducting a study on the treatment of 11 cases of advanced PPGL with acitinib 4 cases of PR and 6 cases of SD The above studies show the preliminary efficacy of various TKI and the effect may be better for SDHB mutations with a controllable safety mainly hypertension In 2017 preliminary results of a prospective clinical study of cabotinib in the treatment of advanced PPGL were reported in the conference abstract ORR of 45 PFS of 11 months and no grade 34 toxicity In summary TKI monotherapy in the treatment of advanced PPGL shows some effect but it is still not satisfactory
There is currently no standard first-line treatment for advanced PPGL NCCN guidelines and Chinas expert consensus 2020 edition recommend the use of tumor reduction surgery palliative resection combined with radiotherapy radionuclide therapy or systemic chemotherapy and other treatment options but the above methods have uncertain efficacy and certain limitations still need to be confirmed by prospective experiments so patients are recommended to participate in clinical trials
13 Application of antirotinib hydrochloride in advanced adrenal pheochromocytomaparaganglioma Allotinib AL3818 is manufactured by Zhengda Tianqing Pharmaceutical Group Co LTD CTTQ Lianyungang Jiangsu China self-developed TKI drugs targeting VEGFR1-3 FGFR1-4 PDGFRα G β rearrangement RET and stem cell factor receptor c-Kit during transfection 26 Anlotinib has shown good anticancer activity in vitroin vitro 27 A multicentre randomized controlled Phase II clinical study of anlotinib in first-line treatment of metastatic renal cell carcinoma mRCC NCT0207203128 showed similar efficacy of anlotinib and Sunitinib There were no significant differences in median PFS 17May vs 16June P 005 OS ORR and DCR P 005 but the toxicity of anrotinib was lower and the incidence of 34 toxicity was significantly lower than that of Sunitinib 289 vs558 P 001 The main symptoms were hypertension and hand-foot syndrome and no hematological toxicity was found In addition Lin J et al also confirmed that anlotinib and Sunitinib had similar efficacy but higher safety TKI treatment of advanced PPGL has a similar mechanism of action but anlotinib safety may be better In addition our team has a certain foundation in the study of anrotinib in the treatment of advanced PPGL In the early stage anrotinib monotherapy was used to treat advanced PPGL in 4 cases and PR in 2 cases 1 case was a SHDB mutation and the adverse reactions were mostly grade 1-2 with hypertension and hand-foot syndrome as the main manifestations Therefore antirotinib may have better efficacy and safety in advanced PPGL which is worthy of further clinical exploration
14 Application of peamprizumab in advanced adrenal pheochromocytomaparaganglioma PD-1PD-L1 monoclonal antibody kills tumors by activating its own normal anti-tumor immune mechanism In 2014 Pembrolizumab achieved results in melanoma officially ushering in the era of global immunotherapy Subsequently indications and significant curative effects were also obtained in multi-tumor species such as non-small cell lung cancer gastric cancer and kidney cancer
PD-L1 is mainly expressed in tumor cells and antigen-presenting cells APCs and is closely related to tumor immune escape 33 PD-L1 receptor of tumor cell membrane binds to PD-1 receptor of T cell membrane which weakens the ability of cytotoxic T lymphocytes to kill tumor cells PD-1PD-L1 mab blocks the above signaling process and restoresactivates the anti-tumor activity of T cells
A study in Peking Union Medical College Hospital 35 showed that 597 were positive for PPGL PD-L1 expression HIS10 and the positive rate of PD-L1 in advanced PPGL was 10011 Study 36 showed that PD-L1 expression was positive in 4 out of 10 advanced PPGL cases 40 Studies indicated that the cytotoxic T lymphocyte infiltration level was increased in advanced PPGL P0092 Therefore PD-1 monoclonal antibody may have some significance in the treatment of advanced PPGL At present only A few cases have been reported in the treatment of advanced PPGL with PD-1 monoclonal antibody The Phase II clinical study conducted by Naing A et al in the treatment of advanced PPGL patients with pembrolizumab showed that 43 4 cases had no progress at 27 weeks 675 months This suggests that PD-1 monoclonal antibody has a certain effect in the treatment of advanced PPGL but PD-1 monotherapy can not meet the clinical needs
KATO Y et al proposed that the effective rate of PD-1 monoclonal antibody in the single treatment of solid tumors was 20-30 and the therapeutic effect was not satisfactory The study of PD-1 monoclonal antibody combined with TKI in the treatment of liver cancer suggests that the combination of PD-1 monoclonal antibody can reverse the immunosuppressor tumor microenvironment in which PD-1 monoclonal antibody is ineffective and assist PD-1PD-L1 monoclonal antibody to activate cytotoxic T lymphocytes The efficacy of acitinib combined with PD-1 mab in the second-line treatment of patients with metastatic renal cancer was significantly higher than that of acitinib ORR 336 vs 201 P0015 PFS 117 months vs 75 months P0002
Piamprilizumab Anicol is a new PD-1 monoclonal antibody developed by Zhengda Tianqing Pharmaceutical Group Co LTD which has been approved for Hodgkins lymphoma RR cHL and squamous non-small cell lung cancer NSCLC indications in China Pembrolizumab has achieved significant efficacy in the treatment of classic Hodgkin lymphoma metastatic nasopharyngeal carcinoma gastricesophageal junction adenocarcinoma and other tumor species in clinical studies with ORR of 894 297 and 263 respectively
Anicol is a humanized IgG1 subtype of PD-1 monoclonal antibody that eliminates Fc effects The IgG1 subtype reduces immune escape by eliminating antibody-dependent cell-mediated cytotoxicity ADCC antibody-dependent cell-mediated phagocytosis ADCP and complement-dependent cytotoxicity CDC The combination of anil with FcR can reduce the occurrence of adverse immune reactions and the incidence of grade 3 and above toxicities such as immune-associated pneumonia hepatitis myocardium and pancreatitis is lower than that of sindillizumab tirellizumab and triplizumab Therefore this study intends to use anicol combined with anlotinib to explore its efficacy and safety in advanced PPGL
15 Application of antirotinib combined with PD-1 monoclonal antibody in advanced pheochromocytomaparaganglioma The combination of TKI and PD-1 monoclonal antibody is a research hotspot in the treatment of advanced tumors Target-free therapy has been widely used in renal urothelial lung liver and other tumors and has achieved remarkable efficacy 46
Only a few cases of combined treatment for advanced PPGL have been reported at home and abroad In Taizhou Hospital of Zhejiang Province in 2022 a patient was treated with palizumab injection 200 mgonce every 3 weeks for intravenous immunotherapy combined with anrotinib 10 mg orally once a day 14 days and 7 days every 3 weeks for a course of treatment The left adrenal mass 96cm 84cm and the multiple intrahepatic mass up to 93cm 88cm were both reduced In the early stage our team used anrotinib combined with PD-1 monoclonal antibody to treat 3 patients and the efficacy reached PR 66 23 including 1 case with SHDB mutation This suggests that targeted immunotherapy for advanced PPGL may have better efficacy
In an open multicenter phase IbII clinical study of anlotinib combined with piamprizumab in the treatment of advanced hepatocellular carcinoma the ORR was 31 and the DCR was 828 The median PFS was 88 months 95 CI 40-123 months 80 were grade 12 toxicity such as elevated AST elevated ALT elevated blood bilirubin etc Only 194 had grade 34 toxicity such as hypertension and rash This is an improvement in efficacy and a decrease in toxicity compared to the treatment of advanced hepatocellular carcinoma with altilizumab combined with bevacizumab or carrilizumab combined with apatinib
At present there have been no studies on the combination of targeted drugs and immunodrugs in the treatment of advanced PPGL at home and abroad Therefore this study will for the first time apply the combination of TKI drugs antirotinib and PD-1 monoclonal antibody Pembrolizumab to metastaticunresectable pheochromocytomaparaganglioma so as to explore the efficacy and safety of combined drugs in the treatment of advanced pheochromocytomaparaganglioma
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None