The three pillars of hematological tumors｜ASCO 2021

ASCO2021 related reports Chinese companies in the field of lung cancer research and development, who is the leader in the field of lung cancer embrace Asia: Junshi nasopharyngeal cancer research selected LBA Yasheng: enter the harvest period digestive tract tumors: conservative advancement According to the statistics of research and development customers, at the ASCO conference, Chinese companies related to blood There are a total of 13 tumor studies, mainly for leukemia, different types of lymphoma and multiple myeloma
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For more detailed analysis of the 2021ASCO annual meeting, please contact mc@pharmaDJ.
com to purchase the PD-1 battle of classic Hodgkin’s lymphoma.
In the study of hematoma, immune checkpoint inhibitors are still the focus
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At the conference, four PD-1/L1 monoclonal antibodies and one CD47 antibody clinical study data were announced
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Among them, the 3 PD-1 monoclonal antibodies are Henri Carrelizumab, BeiGene Tielelizumab, and Kangfang Bio-Peamprolizumab
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The published data of the three products are all phase II clinical research data, and they are all aimed at classic Hodgkin's lymphoma (cHL)
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For the development of PD-1 monoclonal antibodies in China, cHL is an important entry point and a competitive battlefield
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Among the domestically produced PD-1s that have been approved for marketing, the first indication for 3 models is cHL
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Both carrelizumab and tislelizumab have been approved for marketing in China
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Carrelizumab announced the results of a combined treatment study with Microchip Bio-Sidamide
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Tilelizumab is a phase II clinical long-term follow-up data
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In addition, the PD-L1 monoclonal antibody being studied by Mibos announced the data of a phase I clinical study
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CD47 target is a new hot area of ​​immunotherapy, and most tumor cells have CD47 overexpression
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At ASCO this time, ImmuneOnco announced the first human trial of its CD47 antibody IMM01, which is an earlier study
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Analysis of the safety and effectiveness of chidamide combined with decitabine and PD-1 carrelizumab in the treatment of carrelizumab + decitabine-resistant classic Hodgkin lymphoma patients An important battlefield for oncology drugs
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This phase II clinical study is a triple regimen of Chidamide + Carrelizol + Decitabine for patients with cHL who are resistant to treatment with Carrelizol + Decitabine
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Chidamide is a histone deacetylase (HDAC) inhibitor.
It was approved for marketing in 2014 for the treatment of peripheral T-cell lymphoma, and in 2019 it was approved for the treatment of breast cancer
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Carrelizumab was approved in 2019 for the treatment of relapsed and refractory cHL
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A total of 19 patients were enrolled in the study, 14 patients completed the evaluation, and the median follow-up time was 5.
7 months
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The results showed that 13 patients responded with an objective response rate (ORR) of 93%, a complete response rate (CR) of 43%, and a partial response rate (PR) of 50%
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The most common side effects are leukopenia (58%), nausea (53%) and hypertriglyceridemia (26%)
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No immune-related side effects were observed
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Tilelizumab for the treatment of relapsed and refractory cHL A phase II clinical long-term follow-up data Tilelizumab was approved for the treatment of relapsed and refractory cHL in December 2019
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A major feature of tislelizumab in the design is to minimize the binding to the Fc segment, which makes it more prominent in R/R-cHL patients who have failed autologous stem cell transplantation (ASCT)
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The phase II study included 70 patients with a median follow-up time of 33.
8 months
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The efficacy data showed that the ORR was 87.
1%, of which CR was 67.
1%; the duration of response (mDOR) was 31.
3 months, and the progression-free survival (mPFS) was 31.
5 months
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Of the 13 patients who had previously received ASCT, 11 patients (84.
6%) achieved CR
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The Phase II clinical data of PD-1 Paimrizumab for the treatment of relapsed and refractory cHL Paimrizumab is currently jointly developed by Kangfang Biological and Zhengda Tianqing
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A marketing application for the third-line treatment of nasopharyngeal cancer has been submitted in the United States recently
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The Fc receptor and complement-mediated utility function are removed from the design of Paimrizumab, and the antigen binding and dissociation rate is slower than that of PD-1 antibodies already on the market abroad
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In this phase II clinical trial, 94 patients with relapsed and refractory cHL underwent 15.
8 months of observation
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The efficacy of 85 patients can be evaluated: ORR was 89.
4%, of which 40 patients (47.
1%) achieved CR
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The median time to remission and median PFS were not reached
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PD-L1 monoclonal antibody MSB2311 has updated phase I clinical safety and efficacy data in the treatment of solid tumors and hematological malignancies in the Chinese population.
MSB2311 is a PD-L1 monoclonal antibody developed by Maebs Biosciences, which has unique pH-dependent recirculation characteristics
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This phase I study focuses on safety and preliminary anti-tumor activity
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A total of 33 patients were enrolled in the study, including 27 solid tumors and 6 lymphomas
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No dose-limiting toxicity was found, and the safety was controllable
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Among the 17 evaluable solid tumor patients, the ORR was 35%, and 6 patients achieved PR
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One patient achieved sustained iPR, and 4 patients had tumor shrinkage
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One patient with lymphoma achieved PR
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Preliminary data of IMM01 in the treatment of relapsed and refractory lymphoma Phase I clinical data IMM01 is a CD47 monoclonal antibody developed by ImmuneOnco.
This phase I clinical trial for relapsed and refractory lymphoma is its first human trial
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The study included many different types of lymphoma, including follicular lymphoma (FL), Hodgkin lymphoma (HL), marginal zone lymphoma (MZL) and large b-cell lymphoma (DLBCL)
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Safety data showed that no dose-limiting toxicity was observed at the highest dose of 1.
0 mg/kg
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Preliminary efficacy data showed that among 12 evaluable patients, 1 case of FL (applied dose 0.
01 mg/kg) reached CR, and the response was maintained for 26 weeks; one case of HL (PD-1 treatment failed, applied dose of 0.
15 mg/kg) reached CR PR, the response was more than 27 weeks; 1 case of MZL (0.
15 mg/kg) reached stable disease (SD), and the response was maintained for 12 weeks; 1 case of HL (0.
5 mg/kg), 1 case of FL (0.
5 mg/kg) reached shrunk SD, The response was maintained for 12 weeks; one case of weekly T-cell lymphoma AITL (1.
0 mg/kg) reached shrunk SD
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The next goal of CAR-T: Multiple myeloma cell therapy has always been of great interest in the application of hematoma, because the response data is usually very prominent and will produce a long-term response
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In this area, China’s overall progress is relatively fast
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At this ASCO meeting, Genxi Biology and Legend Biology announced the CAR-T product data
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Genxi Biology GC012F and Legend Biology’s cilta-cel both target the BCMA target
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BCMA is widely present in multiple myeloma cells, so CAR-T products targeting BCMA are mostly used in the treatment of multiple myeloma (MM)
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This target is also the most popular CAR-T development direction after CD19
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The long-term follow-up data of GC012F in the treatment of relapsed and refractory MM multi-center clinical GC012F, developed by Genxi Biotechnology, is a BCMA/CD19 dual-targeting autologous CAR-T cell therapy
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The data released this time is its first human clinical study
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The clinical is an IIT study, a total of 19 patients were enrolled at 3 dose levels: 1x10^5/kg (DL1) n=1, 2x10^5/kg (DL2) n=9, 3x10^5/ kg (DL3) n=9
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The efficacy data showed that the ORR reached 94.
7%, and the patients who responded had good VGPR (excellent partial remission) and even achieved complete remission in a strict sense
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In the high-dose group, all patients (n=9) achieved minimal residual disease negative-strictly complete remission (MRD-sCR), and the response was maintained for 6 months or longer
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cilta-cel treatment r/r MM clinical study CARTITUDE-1 data update 2) The data
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cilta-cel is a CAR-T product developed by Legend Bio which targets BCMA (dual epitope binding).
In 2017, Legend Bio and Janssen launched a cooperative development for it.
In December 2020, it submitted a rolling application for a biologics license to the FDA.
(BLA), the listing application is based on the research results of CARTITUDE-1
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CARTITUDE-1 is a phase 1b/2 clinical trial.
97 patients were enrolled and the median follow-up time was 12.
4 months
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The efficacy data showed that the ORR reached 97%, and 67% reached sCR
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Among 57 patients with evaluable MRD, 93% achieved minimal residual disease negative (MRD-negative)
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The median time to first remission was 1 month (1-9), and the median time to CR/sCR was 2 months (1-15)
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77% of patients achieved 12-month PFS, and 89% of patients achieved 12-month overall survival
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CARTITUDE-2 is a phase II clinical study that evaluated MM patients who had previously received 1 to 3 lines of treatment.
20 patients were enrolled and followed up for 5.
8 months
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Efficacy data showed that ORR was 95%, 75% reached sCR/CR, and 85% reached VGPR
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The median time to first remission was 1 month, and the median response time to achieve the best remission was 1.
9 months
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All 4 patients with evaluable MRD reached MRD negative
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Diverse choices of small molecule inhibitors In addition to immune checkpoint inhibitors and cell therapy, small molecule inhibitors are also a very important direction in hematoma research
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At the ASCO meeting, many companies released research results on small molecule inhibitors for the treatment of hematoma
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The target distribution of these products is relatively wide and diverse, including some very popular and classic areas such as Bcl-2, BTK and PI3K
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Yasheng Pharmaceutical, which focuses on the development of apoptosis pathway products, announced the data of the first human clinical study of the Bcl-2 inhibitor APG-2575
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BeiGene announced a phase II clinical preliminary data of its leading product BTK inhibitor Zebutinib, which can give a glimpse of the corner of its product competitive strategy
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Deqi released the Phase II clinical data of the introduced product with its novel mechanism
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Two other companies respectively released early clinical data of PI3K inhibitors
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PI3K-AKT-mTOR is a pathway that plays an important role in tumor cell proliferation, survival and tumor microenvironment.
Drug research on this pathway is one of the hottest topics in recent years
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APG-2575 is a global multi-center, open phase I single-agent study in the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and other hematological malignancies.
APG-2575 is a Bcl-2 inhibitor developed by Ascent Pharmaceuticals , Its two indications (WM and CLL) have been approved by the US FDA for orphan drug qualification
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Currently, only Venetoclax in this target field has been approved for the market
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This phase I clinical study is the first human study of the product
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35 patients were enrolled, including R/R CLL/SLL (n=15), MM (n=6), FL (n=5), Waldenstrom's macroglobulinemia WM (n=4), and acute myeloid system Leukemia (AML), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), myelodysplastic syndrome (MDS) or hairy cell leukemia (HCL) (n=1 respectively)
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The efficacy results showed that among 14 evaluable R/R CLL/SLL patients, 12 achieved PR, ORR was 85.
7%, and median response time was 3 cycles
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A decrease in the absolute lymphocyte count (ALC) can be observed when the dose of APG-2575 is as low as 20 mg/day
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In terms of safety, no dose-limiting toxicity was observed at the highest dose of 1200 mg
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There are no clinical or laboratory reports of tumor lysis syndrome (TLS)
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Preliminary results of a phase II clinical study of Zebutinib on B-cell malignancies that are treated and intolerant to ibrutinib and/or acarabutinib.
Zebutinib is a BTK inhibitor developed by BeiGene.
MCL has been approved in the United States, MCL and CLL/SLL in China
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The Phase II clinical announcement published on ASCO is for patients with lymphoma who are intolerant to ibrutinib, acalabutinib, or both
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A total of 44 patients were enrolled in the study, including 34 CLL, 6 WM, 2 MCL, and 2 marginal zone lymphoma
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Past treatment status: 39 patients only received ibrutinib treatment, 4 patients received ibrutinib and acarabatinib treatment, and 1 patient received only acarabutinib treatment
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The results showed that the median duration of treatment was 4.
2 months
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Eighty-three percent of ibrutinib-tolerant patients and 78% of acarabutinib-resistant patients did not relapse after applying zebutinib
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BTK is already a fiercely competitive field.
Zebutinib's main competitive strategy is to seek the best.
In addition to conducting head-to-head research, the above research can show that it is laying out all the space it can occupy
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Recently, BeiGene announced the specific data of Zebutinib's head-to-head study of ALPINE for CLL/SLL: The median follow-up time was 15 months, and Zebutinib achieved a higher ORR (78.
3% vs 62.
5%, P =0.
0006); For patients with 17p- with a poor prognosis, the ORR advantage is more obvious (83.
3% vs.
53.
8%)
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At the same time, Zebutinib showed a more advantageous 12-month PFS (95% vs 84%, p=0.
0007), which significantly reduced the risk of disease progression by 60%
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The latest results of MARCH Phase II clinical study of ATG-010 for the treatment of rrMM in China ATG-010 is an XPO1 inhibitor
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One of the four products introduced by Deqi Pharmaceuticals in cooperation with Karyopharm Therapeutics in 2017 has been launched in the United States in 2019
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It is the first and only marketed drug in this target field
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The MARCH trial is ATG-010 combined with dexamethasone (Sd regimen) for the treatment of relapsed and refractory MM
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According to the analysis of the first batch of 60 patients, the median follow-up time was 9.
5 months
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The results showed that the ORR was 26.
7%, and the median DOR was 4.
6 months
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The ORR of Sd regimen was 33.
3% in patients exposed to three types of drugs (immunomodulators, proteasome inhibitors, and CD38 monoclonal antibodies), and in patients who had previously received CAR-T therapy, the ORR reached 44.
4%
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In patients with MM who had received immunomodulators (IMiDs) and proteasome inhibitors (PIs) and still relapsed, the data from the MARCH trial was consistent with the STORM trial (supporting product launch in the United States)
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WX390 is a phase I clinical treatment of relapsed and refractory solid tumors and lymphomas.
WX390 is an mTOR/PI3K dual target inhibitor developed by Chenxin Pharmaceutical
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The study announced this time is its first human clinical trial, enrolling a total of 25 patients, distributed in 6 dose levels (0.
1mg, 0.
2mg, 0.
4mg, 0.
7mg, 1.
1mg, 1.
4mg)
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There was no dose-limiting toxicity from 0.
1 to 1.
1, and dose-limiting toxicity was found at 1.
4 mg
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In terms of efficacy, among the 14 patients with evaluable efficacy, 3 patients had confirmed PIK3CA mutations.
All 3 patients showed tumor shrinkage, and 2 patients with solid tumors achieved PR
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Six patients achieved SD, including one FL patient
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A phase Ib clinical study of linperlisib in the treatment of relapsed and refractory peripheral T-cell lymphoma.
Linperlisib is a highly selective PI3Kδ inhibitor developed by Yingli Pharmaceutical
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The announcement this time is a phase Ib clinical study of the product for peripheral T-cell lymphoma
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A total of 36 patients were included in the study
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Of the 27 patients with evaluable efficacy, 19 patients responded with an ORR of 70.
4%, of which CR was 25.
9% and PR was 44.
4%
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Among the two main subtypes of peripheral T-cell lymphoma, the ORR of PTCL-NOS is 50% (6/12), and the ORR of AITL is 80% (8/10)
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The disease control rate can reach 100%
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