echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Medical News > Latest Medical 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: 2020-07-29
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    Adcetris (Vibutuxixmonodis) was approved for listing in China, the three domestic PD-1 antibody drugs with Hodgkin's lymphoma as the initial indications, PD-1 antibodies or other have a chance 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 lymphomasClassic Hodgkin's lymphoma (cHL) accounts for 95% of the HLEpidemiological characteristics in the West and China is not a small gap, the incidence of lymphoma in China is also on the rise, the current incidence rate of about 6.68 per 100,000 people, of which the incidence of HL is about 0.6 per 100,000 peopleFirst-line radiotherapy and chemotherapy ABVD (amycin-bolymycin-plus-changchun-new-base-dakabaquin) after receiving autologous stem cell transplantation ASCT has been able to reach a patient's 5-year survival rate of more than 80%, but some patients have poor tolerance;At present, cHL new drug development has 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 intoleranceSingle-arm clinical trials accelerate the use of PD-1/L1 inhibitors in The Use of R/R cHL in addition to chemotherapy, and with the increase in molecular biology of cHL, a number of new therapeutic targets have been identified, including CD30, which is specific ally of cHL's RS cells, while limited expression in other common cells has become an ideal target for the treatment of HLThe antibody coupling (Brentuximab vedotin), or BV, targeting CD30, was approved by the FDA in August 2011 for R/RCHL patients with FAILed ASCT or at least two multidrug chemotherapy regimens that failed and not suitable for ASCTIt became the first new drug approved for the treatment of cHL since 1977 and has also redefined the treatment landscape for cHLThe overexpression of PD-L1 on RS cells binds to PD-1 expressed on T cells to induce immune checkpoint inhibition and cause T-cell inactivationImmunocheckpoint inhibitors such as PD-1 antibody drugs used in HL have also shown good effectivenessNivolumab and Pembrolizumab were also approved for listing through the same effective endpoint ORR, but the two were included in a more group of subjects in the Phase II trial to explore, which also determined that the people who were later approved were slightly differentNivolumab 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 Pembrolizumab had included two types of ASCT failures in Keynote-087, including unaccepted and accepted BV, in addition to those who did not accept ASCTThis is a highly unsatisfied group that ultimately makes nivo's approved R/R cHL people have to accept ASCT failures, and pembro's approved crowd has no limit on whether or not to accept ASCTCurrently, three approved domestic PD-1 inhibitors have chosen R/R cHL as a conditional listing for initial indications, and two are in the process of listing application reviewFrom the published trial data, the trial group did not limit ASCT failure or inappropriate, 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 could afford ASCT treatment, and at that time BV was not approved for listing in China, so the number of patients treated was relatively smallThe median follow-up time was also shorter, at approximately 12 months, while Nivo and Pembro both reached more than 24 months, making ORR superior to Nivo and PembroPD-1 antibody drugs approved for R/R cHL effectiveness Results The PD-L1 antibody drug is now also in the R/R cHL development tide, the cornerstone CS-1001 will be listed as cHL in 2020, avelumab, durvalumab and attezolizumab are also in clinical trialsPembrolizumab hit Adcetris at present, PD-1 antibody drugs have been considered the post-a-treatment option of Adcetris, however, in the Phase III KEYNOTE-204 trial, Pembro compared with BV head-to-head for PATIENTs with R/R CHL patients who were not suitable or relapsed by ASCT, with a 12-month PFS rate at the main endpoint, with Pembro better than BV, at 53.9% and 35.6%, respectively And show edified in all subgroup populations In addition, ORR was better than the BV group 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 with Keytruda also reported lower level 3 and higher treatment-related adverse events (TRAE) The underlying results of the KEYNOTE-204 trial Based on Pembro's approved cHL one-arm trial Keynote-087 ORR data, MSD decided to conduct a head-to-head trial with Adcetris was a big win, Keytruda showed better anti-tumor efficacy and greater toxicity, which is needed for infirmized patients in the treatment, adding treatment options, but whether it means that Pembro will eventually shake Adthith' treatment position In March 2018, Adcetris combined chemotherapy protocol AVD (amycin, changchunshinal and dacarbazine), was approved as a CD30-positive first-line treatment for adult patients with HL In the trial, called ECHELON-1, 1,334 R/R cHL patients were included, and the Adcetris-AVD treatment group significantly improved mPFS (HR-0.770, p-0.035) compared to the ABVD treatment group 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, single medicinal and relapsed population, but also may be associated with PD-1 antibody drugs for use in R/R populations It's still a long way to go for Pembro to 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 were approved for listing in China on May 14 this year Adcetris sales in North America According to the current Clinical Development Program of 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 Program Clinical Development Progress of Other cHL New Drugs CHL mainly in the mechanism of researching new drugs at present in the clinical late stage of other major drug research targets or concentrated on CD30 In addition to CAR-T and ADC, the mechanism has been innovative in the development of Affimed's first CD30/CD16A dual-specific antibody - AFM13, CD16A is the membrane surface receptor for NK cell expression, so AFM13 can be combined with CD30-positive lymphoma cells and NK cells at the same time, mobilizing NK cells to destroy tumor cells A single drug is currently under way for Stage II clinical trials of R/R cHL after BV and PD-1 antibody therapy, and Phase I clinical trials with Pembro for R/R cHL after BV treatment At the 2019 International Conference on Malignant Lymphoma (ICML), the results of the IB trial conducted jointly by AFM13 and Pembro in R/R cHL patients were announced, with the median of 30 patients in the group receiving 4-line treatment, with an ORR of 88%, of which CR reached 46% The results of this trial support the conceptual validation of NK cells in combination with immunocheckpoint inhibitors Currently, AFM13 has been granted orphan drug qualification by the FDA the mechanism of action of double anti-AFM13 Currently being mainly clinically targeted CD30 new drug CD25 in RS cells and regulatory T cells are expressed, Camidanamlum tesirine is a DDc developed by ADC Therapeutics, and the single resistance (HuMax®-2Ra) of target CD25 (IL-2Ra) 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 The results of Phase I trials in patients with monopharmaceuticals and R/R cHL were published on ICML in 2019, administered every three weeks, and the ORR in the 45?g/kg dose group reached 86.5 percent, and this dose group reached more than 80% of orR in all sub-group populations After two cycles of Q3W administration at Camidanlumab tesirine in Key Phase II, 30?g/kg Q3W continued to improve treatment tolerance But the previous Phase II trial was partially suspended by the FDA because of toxicity issues, including guillalyn-Barr?, a rare neuropathy, that could not be included in the new subjects until July 7 this year, when the FDA canceled the suspension 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, so that tumor cell immunosimmunity is insufficient, affecting the efficacy of immunotherapy, histone deacetylase (HDAC) inhibitors can inhibit RS cell release of chemats, and currently found that Class I HDAC inhibitors, including entinostat, 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
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Related Articles

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.