Stop early? PD-1/IDO1 combination therapy phase III clinical trial encounters Waterloo
Stop early? PD-1/IDO1 combination therapy phase III clinical trial encounters Waterloo April 9, 2018 Source: Original network of Nemi: Knowing and Doing On April 6, 2018, Merck and Incyte jointly issued a statement regretting that their joint PD-1/IDO1 combination therapy, Keytruda/Epacadostat, failed to reach phase III clinical trials for the treatment of unresectable or metastatic melanoma. The primary endpoint was that the clinical trial was stopped early on at the suggestion of the eDMC. Some people can't help but question the status of IDO1 inhibitors in cancer treatment. Not only Incyte's share price fell 23% on the same day, but the price of Incyte competitor Newlink fell 44%, but Incyte said it will learn from the failure to continue IDO. Research on cancer therapy. In recent years, immunotherapy, especially PD-(L)1 therapy, has brought hope to cancer treatment. Major pharmaceutical companies not only strive to develop their own immunotherapy, but also consider combination therapy as an important position. In the ongoing PD-(L)1 clinical combination therapy research, the main combined use includes other tumor immunotherapy, CAR-T products, chemotherapy drugs, small molecule inhibitors, cancer vaccines, etc., but recently it has received much attention. The frustrating news in the PD-1/IDO combination therapy clinical trial. On April 6, 2018, Merck and Incyte Corporation jointly announced their combination therapy. Merck's PD-1 drug Keytruda is combined with Incyte's indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor Epacadostat. The results of Phase III clinical trials of excisional or metastatic melanoma, although their safety data were consistent with previous clinical studies, did not reach any of the dual primary endpoints in this phase III clinical study. Compared with Keytruda monotherapy, Keytruda and Epacadostat did not improve progression-free survival (primary primary endpoint) and the patient's overall survival (secondary primary endpoint) did not reach statistically expected results. Under the advice of the eDMC, Merck and Incyte have suspended early clinical trials. The phase III clinical trial, ECHO-301/KEYNOTE-252, was a randomized, double-blind, placebo-controlled study comparing Keytruda with Epacadostat and placebo for unresectable or metastatic melanoma. . After screening for 700 patients with PD-L1 expression and BRAF gene mutation, the dual primary endpoints of this phase III clinical trial were progression-free survival and overall survival. The key secondary endpoints included objective response rate and safety. Sex and drug resistance. Prior to this, people have been expecting the application of IDO inhibitors in tumor immunotherapy. At the ESMO 2017 conference in September 2017, Incyte announced the combination of Keytruda and Epacadostat in the treatment of advanced melanoma I/II clinical study ECHO- Positive results of 202/KEYNOTE-037, all patients (including newly diagnosed and treated patients) had an objective response rate of 56%, a complete response rate of 14%, a partial response of 41%, a disease stabilization rate of 16%, and a disease control rate of 71%. . According to the excellent clinical data of ECHO-202/KEYNOTE-037, the potential ability of Keytruda and Epacadostat in the treatment of advanced melanoma will exceed the PD-L drug Opdivo and CTLA4 drug Yervoy of BMS. However, the III phase clinical trial ECHO has received much attention. -301/KEYNOTE-252 was badly affected by Waterloo! The failed Phase III clinical trial aggravated the question of IDO inhibitors. On the day of the trial, Incyte's share price immediately fell 23%, and NewLink, which relied entirely on IDO research, fell 44%. This made NewLink have to issue a statement on the same day to save the field, saying that its IDO inhibitor Indoximod has different mechanisms of action to improve the patient's clinical, and also said that there are data showing that Indoximod has the potential to benefit patients, these clinical data It will be announced at the upcoming AACR meeting, hoping that people will not lose confidence in the IDO field. Clinical trials do not always follow a predetermined direction. ECHO-301/KEYNOTE-252 is the first key clinical study of IDO inhibitors, but it has also been a case of clinical research failures, such as IDO inhibitors abandoned by Pfizer due to failure to be effective in clinical phase I of brain cancer, also because The IDO inhibitor GDC-0919, which was abandoned by Roche/Genentech, was not reached in the clinical phase II study of breast cancer. It must be said that the mechanism of action of IDO inhibitors is still not clear. Scholars who are currently conducting mechanism research believe that IDO1 can prevent the detection of tumor cells by the immune system, so that the immune cells can be enhanced by blocking the IDO1 pathway. Response rate. Merck and Incyte said that they are working with reviewers to properly house other patients who are participating in the trial, as well as data collection and analysis as soon as possible. Merck's senior VP Roy Baynes said in a statement, "We look forward to sharing the comprehensive and comprehensive data analysis results of ECHO-301/KEYNOTE-252 with various scientific teams in the upcoming medical conference." Incy's CMO Steven Stein believes the failure A stepping stone to success, “all ECHO-301/KEYNOTE-252 data will help us understand the role of IDO inhibitors in combination with PD-1 drugs, and may also broaden Epacadostat's project progress. We will also Continue to work on the improvement of cancer therapy and the mechanism of action of IDO1 inhibitors, as well as develop new mechanisms to improve the living conditions of patients." The suspension of ECHO-301/KEYNOTE-252 clinical trials can only be described as a temporary failure, which will not only deepen people's understanding of the mechanism of action of IDO inhibitors, but also the case of IDO clinical trials that have been or will be carried out. With a fine-tuning of the experimental design, I believe many scholars are looking forward to the upcoming data sharing from Merck and Incyte. Reference source: 1.UPDATED: Keytruda/epacadostat combo crashes in PhIII melanoma study, raising questions about the future of IDO for Incyte; 2.Body blow for Incyte as Merck-partnered melanoma trial bombs; 3.NewLink Genetics Announces Review of Clinical Programs; 4. Incyte and Merck Provide Update on Phase 3 Study of Epacadostat in Combination with KEYTRUDA® (pembrolizumab) in Patients with Unresectable or Metastatic Melanoma. Fireproof Safe is a good choice. It can not only provide a safe storage space for these articles, but also protect these articles from loss in the event of unfortunate fire. Steel anti-theft safety fireproof safe adopts special sealing technology and fire prevention materials, which can prevent fire source from entering its interior and maintain the integrity and safety of articles. In addition to fire prevention, electronic fireproof safe can also effectively prevent damage to water, dust and other articles. Our fireproof safe has a fire test report, which can effectively prevent external heat and smoke and prevent internal articles from being damaged in the fire test. The Paper documents in the box are not damaged within one hour of internal melting point 177 ℃. 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