The field of hepatobiliary is the most desirable three target new drug introduction, so that liver cancer patients have more choices!

Recently approved the market of FGFR2 target drug pemigatinib, Peugeot liver and bile tumors into the new world of precision target treatment, what is the future to look forward to the new direction? This is to introduce three potential new targets of liver and bile, VEGF, IDH1/2 and FGFR2, as well as new drugs for these three targets, Tivozanib, ivosidenib and infigratinibAll three drugs were highly competitive target drugs in the liver and bile field, with DCR at 63%, 53% and 83.6%, respectivelyIt is hoped that these targeted drugs will be put on the market as soon as possible for the benefit of more patients with liver and bile tumors1, Tivozanib first-line treatment of advanced liver cancer, ORR 21%, DCR63%British Journal of Cancer reported the results of a trial of a new anti-angiogenic inhibitor drug Tivozanib single-line treatment of liver cancerTivozanib is an oral inhibitor of VEGFR-1/2/3Compared to Sorafenib:1tivozanib is a powerful, highly selective inhibitor of VEGFR-1/2/3 designed to optimize blocking potential while minimizing non-target effects2And compared to Sorafeni, it has a much longer half-life and is allowed to be taken once a day3Unlike Sorafini, it does not interact with CYP3A4 inhibitorsIt has no associated liver toxicity or tissue build-upTo further verify the safety and efficacy of the drug in patients with advanced HCCthis clinical trial has conducted an open label phase 1b/2 trial in patients with advanced liver cancerThe trial included 33 patients with advanced HCC without systemic treatment and evaluated the efficacy of 19 patientsThe study followed a 3-3 design, starting with 1 mg (dose level 1, DL1), with a planned upgrade to 1.5 mg (DL2) and allowing for degradation to 0.5 mg (DL1)Tivozanib is taken orally once a day, with the recommended stage 2 dose (RP2D) set at 1 mg/os per day and discontinued for 7 days over a 28-day cycleThe median follow-up time was 37.3 monthsresults:1Median PFS was 24 weeks, 24 weeks PFS rate was 58% (90% CI: 33-76, Figure 1a), and there were 4 patients with no disease progression for more than 2 years2Median OS is 9.0 months (Figure 1b), with 40% and 30% OS rates for one year and 2 years, respectively3The objective mitigation rate orRR is 21% (n-4) and the overall disease control rate is 63% (Figure 2)Of these, 4 patients achieved partial remission PR and 8 (42%) had stable diseases (S D)Most patients had imaging evidence of tumor reduction, and 18 patients were sampled for baseline and therapeutic serum AFP measurementsIn 4 patients, AFP decreased by 50%AFP decreased by 50% of patients with longer PFS and OS (not statistically significant) safety: overall, tivozanib was well tolerated The main adverse reactions were fatigue (63%, 3-4:26%), diarrhea (41%, 3-4:0%), decreased appetite (37%, level3 and 4: 3.7%), and no toxic death was observed With the success of antiangiogenic inhibitors and "T-A", several clinical trials are currently evaluating the combination of anti-VEGF drugs and immunocheckpoint inhibitors for advanced liver cancer, and research is also being conducted on tivozanib in combination with PD-L1 inhibitor durvalumab II, IDH1/2 New Drug Tibsovo for the treatment of bile duct cancer, DCR 53% Agios Pharmaceuticals announced at this year's ESMO conference that the company's IDH1 inhibitor Tibsovo (ivosidenib), in the treatment of bile duct cancer, the stage 3 clinical trial ClarlHyHy Tibsovo significantly improved the progressionless survival (PFS) period in patients, reducing the risk of disease progression or death by 63% The company plans to submit an application for a new drug (sNDA) by the end of the year received 1-2 systemic treatments in a global randomized Phase 3 clinical trial called ClarlDHy, but patients with bile duct aloma (carrying the IDH1 gene mutation) whocontinued the disease were divided into two groups, one receiving Tibsovo and the other receiving placebo treatment As of January 31, 2019, 124 patients were in the Tibsovo group and 61 patients were in the placebo group results showed that the progression-free survival (PFS) in the Tibsovo group was 2.7 months and the placebo group was 1.4 months (HR-0.37, 95% CI:0.25-0.54, p 0.001) The progression-free survival rate of 6 months in patients in the Tibsovo group was 32% and the non-progressive survival rate was 22% in 12 months The disease control rate was 53% in the Tibsovo group and 28% in the control group The median OS in the Tibsovo group was 10.8 months, better than 9.7 months in the placebo group (HR:0.69, 95% CI: 0.44-1.10, p-0.06) 3, FGFR new drug infigratinib, DCR is 83.6%! the last thing i have to mention is the star target of bile duct cancer, FGFR2, although there is already a marketed pemigatinib, but if there are more options, I believe the more likely it is for patients to benefit Share another new drug for FGFR2 today Infigratinib (BGJ398) is a selective fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor administered by the FDA in early January 2020 The latest results of the Phase II study show controlled toxicity and clinically significant activity in patients with advanced bile duct cancer who have previously failed chemotherapy and fGFR2 fusion have been treated with Infigratinib the trial recruited 71 patients with FGFR2 fusion/translocation, taking 125 mg of infigratinib daily, 21 days or ally, 28 days for one cycle the results of the trial: 1, 18 patients (25.4%) were partially alleviated, 41 (57.7%) were stable, and 8 (11.3%) had disease progression 2, DCR was 83.6% (95% CI, 72.5%-91.5%), median DoR was 5.4 months (95% CI, 3.7-7.4), median PFS was 6.8 months (95% CI, 5.3-7.6), and median OS was 12.5 months (95%, 95.96.6.6.6) 3, adverse reactions: the most common TRAE is hyperphosphateemia, occurred in 73.2% of patients other common TRAEs (all levels) include fatigue (49%), stomatitis (45%), hair loss (38%) and constipation (35%) 3/4 level TRAE are common in hypophosphateemia (14.1%), hyperphosphateemia (12.7%) and hyponatremia (11.3%) references: 1, Fountzilas, C., Gupta, M., Lee, S et al A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma Br J Cancer (2020) http://dx.doi.org/10.1038/s41416-020-0737-6 2, https:// Author: International Hepatobiliary Information Source: International hepatobiliary Information wonderful review: njwbhuang in 2020-5-4 comment: good news! 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