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    Home > Medical News > Medical World News > What new options are available for new drugs for Hodgkin's lymphoma after the PD-1 antibody fight?

    What new options are available for new drugs for Hodgkin's lymphoma after the PD-1 antibody fight?

    • Last Update: 2020-08-03
    • Source: Internet
    • Author: User
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    Wen/April ChenAdcetris (Vibutuximonoditis) was approved for sale in China, the three domestic PD-1 antibody drugs were listed as the first indications of Hodgkin's lymphoma, pD-1 antibodies or other opportunities to break through the Adcetris market? Lymphoma is a malignant tumor that originates in the lymphatic hematopoietic system, of which about 10% is Hodgkin's lymphoma (HL), characterized by RS (Reed-Sternberg) cells, and the remaining LYmphomas without RS cells are non-Hodgkin lymphomas.
    Classic Hodgkin's lymphoma (cHL) accounts for 95% of the HL.
    epidemiological characteristics in The gap between China and the West is not large, the incidence of lymphoma in China is also on the rise, the current incidence rate is about 6.68 per 100,000 people, of which the incidence of HL is about 0.6 per 100,000 people.
    first-line radiotherapy and chemotherapy ABVD (amycin-boramycin-and-combination-and-daba-in-autologous-daba-in-patient) has enabled the patient's 5-year survival rate to reach more than 80%, but some patients have poor tolerance;
    current development of cHL new drugs in two main directions: one is to join the first-line treatment to reduce the use of chemotherapy drugs, and the other is for the initial treatment of patients withno-answer or intolerance.
    single-arm clinical trials accelerated the use of PD-1/L1 inhibitors in addition to R/R cHL in the course of chemotherapy, with the increase in molecular biology of cHL, identified a number of new therapeutic targets, including CD30, its surface-specific expression of RS cells in cHL, and limited expression in other common cells, becoming an ideal target for treatment of HL.
    the antibody coupling (Brentuximab vedotin) targeting CD30 was approved by the FDA in August 2011 for R/R c patients with ASCT that failed or at least two multidrug chemotherapy regimens failed and were not suitable for ASCT.
    became the first new drug approved for cHL since 1977 and has redefined the treatment landscape for cHL.
    the overexpression of PD-L1 in RS cells combined with PD-1 expressed on T cells, induced immune checkpoint suppression and caused T-cell inactivation.
    immunological checkpoint inhibitors such as PD-1 antibody drugs used in HL have also shown good effectiveness.
    Nivolumab and Pembrolizumab were also approved for listing through the same effective endpoint ORR, but both were explored in phase II trials by including more groups of subjects, which also determined that the people who were subsequently approved were slightly different.
    Nivolumab included three groups of people who had failed to accept ASCT in the Chekmate-205 trial, one that did not accept BV after receiving ASCT, had accepted BV, had accepted BV, or accepted BV before or after ASCT, and that Pembrolizumab had included two types of ASCT failures in Keynote-087, including those who had not accepted and accepted BV, in addition to those who did not accept ASCT.
    this is a highly unsatisfied crowd that ultimately makes nivo's approved R/R cHL people have to accept the ASCT failed, and the Pembro approved crowd has no limit on whether or not to accept ASCT.
    currently has three approved domestic PD-1 inhibitors selected R/R cHL as a conditional listing for initial indications, and two are currently in the process of listing application review.
    from the published trial data, the trial group did not have ASCT failure or inappropriate restrictions, and the proportion of patients who received ASCT or BV in the included population was less than 20%, due to the low proportion of patients in China who can afford ASCT treatment, and at that time BV has not been approved for listing in China, so the number of patients treated is relatively small.
    median follow-up time is also shorter, at about 12 months, while Both Nivo and Pembro are more than 24 months, making ORR superior to Nivo and Pembro.
    PD-1 antibody drugs approved for R/R cHL effectiveness results The pD-L1 antibody drug is currently in the R/R cHL development tide, the cornerstone CS-1001 will be listed as cHL in 2020, avelumab, durvalumab and atezolizumab are also in clinical trials.
    Pembrolizumab hit Adcetris at present, PD-1 antibody drugs have been considered as the post-treatment option sedcetris, however, in The Grade III KEYNOTE-204 trial, Pembro compared with BV head-to-head, for ASCT unsuitable or relapsed R/RCHL patients, the main endpoint 12 months PFS rate, Pem is better than BV, 53.9% and 35.6%, respectively.
    and showed good results in all subgroup populations.
    , ORR also outperformed BV in Pembro group at 65.5% and 54.2%, respectively, with Pembro's median mitigation duration of 20.7 months and BV at 13.8 months. patients treated
    Keytruda also reported lower level 3 and higher treatment-related adverse events (TRAE).
    keynote-204 trial effectiveness results are based on Pembro approved cHL's one-arm trial Keynote-087 ORR data, MSD decided to conduct head-to-head trials with Adcetris is a big win, Keytruda showed better anti-tumor efficacy and greater toxicity, which is needed in the treatment of weak patients, for patients to increase treatment options, but does this mean that Pembro will eventually shake Adthtris in the treatment position.
    a dcetris joint chemotherapy program AVD (amycin, changchun shinol and dacabaquine) in March 2018, was approved as a CD30-positive first-line treatment for adult patients with HL.
    in a trial called ECHELON-1, 1,334 R/R cHL patients were included, and compared to the ABVD treatment group, the Adcetris-AVD treatment group significantly improved mPFS (HR-0.770, p-0.035).
    at the same time, BMS is also carrying out a trial called CheckMate 812, Adcetris and Nivo combined with a comparison of Adcetris monomedicine and R/R cHL patients, it can be seen that Adcetris can not only be used with chemotherapy, monomedicine and relapse population, but also may be associated with PD-1 antibody drugs for Use in R/R populations.
    Pembro still needs a long way to go before he can make it to the cHL treatment market.
    sales in North America reached $630 million in 2019 and sales of HL treatment in Japan grew to about $490 million, and was approved for listing in China on May 14 this year.
    Sales in North America based on the current clinical development program for Adcetris, in addition to working with Nivo to push first-line treatment to early-stage patients, there are plans to expand to the adolescent population, single-drug challenge Adcetris discontinued treatment.
    Adcetris in the HL clinical development plan other cHL new drug clinical development progress cHL mainly in the mechanism of researching new drugs is currently in the clinical late stage of other mainly in the research drug target or gathered on CD30.
    in addition to CAR-T and ADC, the mechanism has been innovative in the development of The first CD30/CD16A dual-specific antibody - AFM13, CD16A is the membrane surface receptor of NK cell expression, so AFM13 can be both closely integrated with CD30-positive lymphoma cells and NK cells, mobilizing NK cells to destroy tumor cells.
    is currently in the course of a single drug for Stage II clinical trials of R/R cHL after BV and PD-1 antibody therapy, and a Phase I clinical trial with Pembro for R/R cHL after BV treatment.
    at the 2019 International Conference on Malignant Lymphoma (ICML), published the results of ib trials conducted jointly by AFM13 and Pembro for R/R cHL patients, with the middle of 30 patients in the group receiving 4-line treatment, with an ORR of 88%, of which CR reached 46%.
    this experimental result supports the conceptual validation of NK cells in combination with immunocheckpoint inhibitors.
    a current AFM13 has been granted orphan drug status by the FDA.
    double anti-AFM13 mechanism of action is currently mainly clinical lying in the research of the target CD30 new drug CD25 in RS cells and regulatory T cells are expressed, Camidanlum ab Tesirine is developed by ADC Therapeutics ADC, by targeting CD25 (IL-2Ra) mono-resistance (HuMax®-HuMax-®-THE TAC, WHICH IS CO-COUPLED WITH THE PYRIDOXATOXIN TETRAPYRITAS (SG3249) OF GENMAB A/S, CAUSES REPLICATION STAGNATION THAT DOES NOT DEPEND ON CELL REPLICATION CYCLES AND EVENTUALLY LEADS TO CELL DEATH.
    published the results of Phase I trials in patients with monomedicine and R/R cHL in 2019, with an ORR of 86.5% in the 45-g/kg dose group, which reached more than 80% of all subgroup populations.
    continue to improve treatment tolerance after two cycles of Q3W administration at the recommended dose of Camidanlumab tesirine in Phase II.
    but the previous Phase II trial was partially suspended by the FDA for a toxicity problem in which patients developed the rare neuropathic Guillain-Barr?, which was unable to include new subjects until July 7 this year, when the FDA called off after assessing safety risks.
    Camidanlumab tesirine Phase I trial effectiveness results RS cells by releasing chemofactors such as TARC to induce or summon Treg cells, making tumor cell immunotherapy inadequate, affecting the efficacy of immunotherapy, histone deacetylase (HDAC) inhibitors can inhibit RS cell release of chemators, and currently found that Class I HDAC inhibitors, including entinost, Mocetinostat, panobinostat and other can increase the expression of PD-L1 in B-cell lymphoma tumor cells, so the possibility of HDAC inhibitors for the treatment of cHL is proposed, given that the previous single drug trial orR is about 30-35%, so HDAC inhibitors are more suitable for the use of a combination of methods to enhance the efficacy of immunotherapy, currently Entinostat is in conjunction with Pembrolib, mothsat and BV.
    .
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