Three new drugs of cornerstone pharmaceutical industry appear in ASCO commercialization transformation
Last Update: 2020-06-19
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Cornerstone pharmaceutical is a rapidly growing biomedical enterprise in China in recent two yearsIt has not only built a competitive cancer drug product pipeline by means of independent research and development + license in two-wheel drive, but also successfully IPO within three years after its establishment, ranking among the leading biomedical companies in ChinaWith the steady progress of clinical product development, cornerstone pharmaceutical industry is in the critical period of upgrading from the R & D stage to the commercial stage, so the clinical data of core products in its pipeline has attracted more and more attention in the industry< br / > cornerstone pharmaceutical product pipeline < br / > source: cornerstone pharmaceutical < br / > at the 2020 ASCO conference, cornerstone pharmaceutical and its partners shared the key clinical data of cs1001 (PD-L1 mAb), avapritinib (Kit / PDGFRA inhibitor), pralsettinib (RET inhibitor) and other three new drugs in the later stage, Let us have a further understanding of the future commercialization prospect of cornerstone pharmaceutical products< br / > cs1001: the results of the first-line treatment of advanced non-small cell lung cancer in phase III are expected < br / > cs1001 is independently developed by cornerstoneIt is a full-length human anti-PD-L1 monoclonal antibody based on omnirat ® transgenic animal platform authorized by ligand company of the United States, and it is the most close to human natural IgG4 monoclonal antibody, Compared with the same kind of drugs, it has the safety advantage of lower immunogenicity and related toxicity riskCornerstone pharmaceutical released the key POC data of phase IB study of advanced non-small cell lung cancer (NSCLC) cohort of cs1001-101 study at the 2020 ASCO conferenceAs of February 19, 2020, 10 patients in NSCLC group achieved partial remission (PR), objective remission rate (ORR) was 47.6%, median progression free survival (MPFs) was 6.5 months, median response duration (DOR) was 8.7 months< br / > as of February 19, 2020, the orr reached 75%, median PFS was 8.4 months, and median dor was 6.4 months< br / > in terms of safety, cs1001 is well tolerated, and there is no case of withdrawal of patients due to cs1001 treatment-related adverse eventsAs of July 1, 2019, 85.7% (18 / 21) of drug treatment-related adverse events (trace) and 28.6% (6 / 21) of trace above level 3 were reported in the non squamous NSCLC cohortThe incidence of immune related adverse reactions (Irae) was 23.8% (5 / 21), all of which were grade 2There were 4 cases with elevated aspartate aminotransferase (AST) and 3 cases with elevated alanine aminotransferase (ALT)The incidence of trans was 90.0% (18 / 20) in patients with squamous NSCLC and 25% (5 / 20) in patients above grade 3The incidence of Irae was 15% (3 / 20), including 2 cases of skin rash below grade 2< br / > in general, cs1001 showed excellent antitumor activity and good safety data in phase IB study which included both non squamous and squamous NSCLC, especially for 75% orr of squamous NSCLC, which was almost the best result of similar products in phase I, which also indicated that cs1001 was expected to obtain ideal efficacy data in phase III study with sample enlargement< br / > at present, cornerstone pharmaceutical has completed the recruitment of patients in the phase III study of cs1001 combined with platinum chemotherapy vs placebo combined with chemotherapy for advanced NSCLC 480 patients are enrolled in the group, and the main research results are expected to be published in a few months This is the first PD-1 / PD-L1 first-line therapy phase III clinical study covering both squamous NSCLC and non squamous NSCLC subtypes in China The results are expected lung cancer is the highest incidence rate and mortality rate in the world and China In 2018, there were about 770 thousand new lung cancer cases and 690 thousand deaths in lung cancer in China Lung cancer has always been an indisputable place in the tumor drug market, and the first-line therapy is the commanding point of lung cancer market competition In NSCLC (85% of lung cancer), non squamous cells account for about 70% and squamous cells account for about 30% If cornerstone pharmaceutical can submit the listing application covering both scaly and non scaly NSCLC after completing phase III research, it will be in a favorable competitive position in the market < br / > pralsettinib: a powerful tool to overcome RET positive solid tumors < br / > pralsettinib is a highly selective single target inhibitor of RET (reactive during transfer) developed by blueprint medicine Cornerstone pharmaceutical entered into cooperation with blueprint medicines in June 2018, introducing the Greater China development rights and interests of pralsettinib Previously, blueprint medicines has submitted the listing application of pralsettinib to FDA and EMA for the treatment of locally advanced or metastatic NSCLC with positive RET fusion Cornerstone Pharmaceutical Co., Ltd completed the first patient administration of pralsettinib global phase I study in China in August 2019, and is expected to submit an application for listing in China in the third quarter of 2020 < br / > RET is a proto oncogene located on chromosome 10 The RET protein encoded by it is a receptor tyrosine kinase existing on the cell membrane When the growth factor combines with the extracellular region of RET, it will trigger a series of intracellular chain chemical reactions, which will cause cell division, maturation and play corresponding functions The differentiation and proliferation of RET fusion positive cancer and RET mutation positive medullary thyroid cancer cells are highly dependent on the activation of RET protein, which is also known as "carcinogenic gene addiction", so RET positive tumors are very sensitive to high selective single target RET inhibitors The incidence of RET gene fusion in NSCLC patients is about 1% ~ 2%, and in papillary thyroid cancer (about 85% of all thyroid cancer) is 10% ~ 20% The incidence of RET gene mutation in medullary thyroid carcinoma is about 60% < br / > the latest pralsettinib data released by blueprint medicine at the 2020 ASCO conference are from the clinical assessment analysis set, including 116 patients with RET fusion positive NSCLC, 11 patients with RET fusion positive thyroid cancer, and 12 patients with other tumor types of RET fusion positive < br / > as of November 18, 2019, the orr of 80 patients with RET fusion positive NSCLC treated with pralsettinib was 61% (95% CI: 50-72), of which 2 PR were to be confirmed as of the date of data but later confirmed 5% of the patients achieved the confirmed Cr, and 14% of the patients achieved the complete regression of the target tumor The Orr and Cr of 26 RET fusion positive patients who had not received systemic therapy were 73% (95% CI: 52-88) and 12% respectively < br / > pralsettinib also showed strong and sustained intracranial antitumor activity in 9 NSCLC patients with measurable brain metastasis at baseline In 9 patients, the CNS metastasis was reduced The proportion of patients with complete remission was 33% (3 / 9) As of the data cut-off date, patients with evaluable brain metastases were treated for up to 12 months, and no new CNS metastases were found at baseline < br / > in conclusion, pralsettinib has the same efficacy and excellent clinical antitumor activity in RET fusion positive NSCLC patients, no matter whether the patients have been treated or not, and whether the patients' RET fusion partner type or CNS has been involved For 116 patients with RET fusion positive NSCLC, the median dor of the patients who achieved remission was not reached (95% CI: 11 months ~ not reached), and 86% of the patients whose dor reached 6 months As of the end of the data period, 74% of patients with confirmed remission (including all patients with CR) are still under treatment < br / > for other types of RET fusion positive tumor patients, pralsettinib also showed significant clinical activity As of February 13, 2020, in 11 patients with RET fusion positive thyroid cancer (10 patients have received systemic treatment), the confirmed orr was 91% (95% CI: 59-100), the disease control rate was 100% (95% CI: 72-100), 70% of the remission patients were still receiving treatment, and the treatment lasted for 22 months Of the 12 patients with other RET fusion positive tumors who had previously received systemic therapy, the orr assessed by the researchers was 50% (95% CI: 21 ‒ 79), with one PR to be confirmed Remission of varying degrees was observed in all evaluable patients with pancreatic cancer (n = 3) and cholangiocarcinoma (n = 2), and these types of tumors usually have poor prognosis < br / > in terms of safety, as of November 18, 2019, a total of 354 patients took part in the clinical trial of arrow, and received pralsettinib once a day at the initial dose of 400 mg The overall security results of pralsettinib are consistent with the previously reported data results Pralsettinib showed good tolerance in all tumor species, and most of the trae were 1 / 2 grade The most common (≥ 15%) of the traes reported by the researchers included elevated ast, anemia, elevated ALT, constipation, hypertension, and neutropenia More than 5% of grade 3 or higher Rae reported by the researchers included hypertension, neutropenia, and anemia Only 4% of the patients stopped pralsettinib because of Rae < br / > at present, the treatment plan for RET fusion mutation tumor is mainly to use multi kinase inhibitors, such as cabotinib and vandetanib Due to the low targeting selectivity, the curative effect is very limited and the toxicity is large From the above data, we can find that pralsettinib can not only bring strong and stable curative effect to ret positive solid tumor patients, but also has a low incidence of adverse events above level 3, and has a very significant survival benefit < br / > pralsettinib has been awarded the qualification of breakthrough therapy by FDA for the treatment of RET fusion NSCLC progressing after platinum containing chemotherapy and RET mutation positive medullary thyroid cancer requiring systematic treatment without alternative treatment scheme After being approved, pralsettinib will provide a new treatment option for such patients Although the proportion of RET fusion positive patients in NSCLC is far lower than that of EGFR mutation, the huge base of lung cancer population and the exact clinical benefits of RET single target inhibitors determine the good market potential of RET inhibitors < br / > avapritinib: to break the drug-free dilemma of patients with advanced gastrointestinal stromal tumors < br / > avapritinib is a kit / PDGFRA inhibitor developed by blueprint medicines Cornerstone pharmaceutical entered into cooperation with blueprint medicines in June 2018, introducing the development rights and interests of avapritinib in Greater China On January 9, 2020, avapritinib was approved by FDA for the treatment of inoperable or metastatic adult gastrointestinal stromal tumor (GIST) patients with pdgfra18 exon mutations, including the most common d842v mutation In April 23rd, cornerstone pharmaceutical filed a listing application in Chinese mainland for avapritinib, which is used to treat adult patients with PDGFRA exon 18 mutation (including D842V mutation), and four line treatment for patients with non surgical resection or metastatic GIST GIST < br / > the approval of avapritinib by FDA is mainly based on the data of navigator study At the 2020 ASCO conference, cornerstone pharmaceutical announced the results of the bridging trial conducted by avapritinib in patients with gist in China This open label, multicenter, phase I / II clinical study included adult patients with unresectable or metastatic GIST who had previously been treated with imatinib and more than one other tyrosine kinase inhibitor or who were intolerant to standard therapy or carrying pdgfrad842v mutation The main purpose of this study was to evaluate the safety, pharmacokinetics and antitumor efficacy of avapritinib < br / > as of December 25, 2019, 12 Chinese GIST patients completed phase I dose escalation study The preliminary results showed that < br / > non resectable or metastatic advanced Chinese GIST patients had good tolerance to avaparinib 200mg and 300mg, and no dose limiting toxicity was observed The safety data is consistent with the previously published global research safety results There is no report of level 4-5 adverse events (AE), no drug-related treatment discontinuation events, and the most common level 3 trace is anemia (n = 2); < br / > avapritinib absorbs rapidly, with a median peak time of 2.0-4.0
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