Nat Med: New Progress in Pancreatic Cancer Treatment! Triple therapy of CXCR4 antagonists , PD-1 inhibitors and chemotherapy, with a disease control rate of 77% in the preliminary trial

Pancreatic cancer is perhaps the hardest hard bone to chew on in immunotherapythick extracellular matrix as a protective shell, highly inhibited immune microenvironment, coupled with sly and sophisticated cancer cells, previously popular PD-1 inhibitors, also can not stage a single-riding Savior's good playbut we still have the trick of "co-operation." Recently released clinical trials (KEYNOTE-202) show that the new CXCR4 inhibitor BL-8040 (Motixafortide), in combination with PD-1 inhibitors and chemotherapy, has had a good initial effect in second-line/third-line treatment of pancreatic cancerthis type of triple therapy, used as a second-line treatment in the trial, the disease control rate reached 77%, of which 35% of patients achieved objective relief, the duration of the relief reached 7.8 months, these data are a rare advance in pancreatic cancer treatment over the yearsThe data are published in Nature Medicinewhy pancreatic cancer is difficult to treat, scientists have come up with a number of reasons, one of the most important is that the tumor microenvironment, the number of CD8-T cells is too smallEven if the immunocheckpoint inhibitor can cross a heavy barrier to reach the tumor site, it is difficult to mobilize a strong enough anti-tumor immune responseso to give PD-1 inhibitors the ability to challenge pancreatic cancer, you have to give them a reliable teammateThe CXCR4 inhibitors used in this trial are the new stars of concern in recent years because many cancer cells have high expression of CXCR4specific to pancreatic cancer, inhibiting CXCR4 can increase the number of T cells in the tumor microenvironment, and also target a large number of tumor-related fibroblasts (CAF) in the outer matrix of pancreatic cancer cellsIn this way, a two-pronged approach can weaken the adverse effects of pancreatic cancer tumor microenvironment on immunotherapyEach of the elements in the graph may have an impact on immunotherapy outcomes (Photo: Nature Reviews Clinical Oncology)animal experiments also show edifying that the combination of PD-1/L1 inhibitors and CXCR4 inhibitors can have collaborative synergies, so having these two drugs work together is a very natural choicethen said the COMBAT trial, which is divided into two parts, the first part is to verify the bl-8040 and Pablo bezumab, as a backline treatment of safety and initial efficacyIn pancreatic cancer, the treatment of three-line and above is very difficult, lack of mature programsa total of 29 patients participated in this trial, the overall disease control rate of BL-8040 and Pablozumab was 34.5%, and only one patient achieved objective remission, which also reflected the "hard bone" of pancreatic cancer but analysis data show that the efficacy is mainly reflected in the second-line treatment of 16 patients, their median survival reached 7.5 months, significantly better than the previous FDA-approved Ilitocone and fluoromyache and calcium folate program survival (6.1 months) a variety of test results also suggested that the treatment of BL-8040 and Pablo beads, increased the level of activated T-cells in peripheral blood, reduced the number of regulated T-cells, immersed in the tumor CD8-T cells also significantly increased based on these results, the research team in the trial part 2 specifically into the group of 22 Gisitabin first-line treatment, the progress of the disease of metastatic pancreatic cancer patients, on the basis of BL-8040 and Paboli bead monoantigen, plus ilitholitomy, fluoruuatine and calcium folate triamcinolone three-drug chemotherapy program treatment had a strong reinforcement of chemotherapy, the effect immediately went up Seven of the 22 patients achieved partial remission, with an objective remission rate of 32%, while the median remission duration reached 7.8 months, significantly better than simple chemotherapy Add 10 patients who sit undeveloped after treatment, the overall disease control rate (DCR), reached 77%! The duration of remission and disease control is not bad
three-drug chemotherapy program in the previous clinical Phase III trials, the objective remission rate and disease control rate were 17% and 52%, respectively And there is no microsatellite instability (MSI-H) in these 22 patients, which is more suitable for immunotherapy patients, so the effect of BL-8040 and Paboli-Zumai-zumaboost boost is less difficult although it appears that there are many drugs, but only two of the 22 patients because of the apparent side effects and the discontinuation of the drug, 3-4 levels of severe adverse events mainly diarrhea and fatigue, the incidence is relatively low Therefore, the team believes that the treatment option is also safe and tolerable but in this paper, no indicators such as total lifetime (OS) and non-progression lifetime (PFS) were published in Part 2 of the experiment How much value the partnership of the BL-8040 and PD-1 inhibitors will be, it will be revealed by follow-up data and trials