Landmark clinical study TOP10 in 2020

In 2020, the pace of approval of new drugs by regulators such as the FDA and NMPA has not slowed, despite the global epidemic of new crown pneumonia.
same time, some of the major clinical findings have been published, glimmers of hope for advances in the treatment of some diseases.
at the end of this year, let's review the landmark clinical study in 2020.
NO.1 Donafinib single-drug first-line treatment of advanced hepatocellular carcinoma Phase III ZGDH3 Research Company: Zeal Pharmaceutical Drug Mechanism: BRAF/VEGFR/PDGFR Multi-Kinase Inhibitor, Zendai Pharmaceuticals January 1, Zeelin Pharmaceuticals announces Donaphone I The phase III ZGDH3 study of line therapy for advanced hepatocellular carcinoma reached the preset main endpoint, and the median total survival (mOS) was significantly better than that of the Solafini control treatment group, which achieved significant extension of statistical and clinical significance, and showed better safety in terms of adverse event rates of level 3 and above, drug-related suspension or reduction.
standard drug for clinical first-line treatment of hepatocellular carcinoma is soraphini, which has not been able to beat soraphinist in a single-drug first-line "head-to-head" for more than a decade since it was approved for the market.
O drug, K drug, etc. are also as a second-line treatment for liver cancer was accelerated approval, but after the listing of the empirical research did not reach the preset end, failed.
Tecentriq-Avastin's joint program broke the deadlock in first-line treatment of hepatocellular carcinoma for more than 10 years, and showed better results than Solaphini in a Phase III study of first-line treatment of non-surgical removal of advanced hepatocellular carcinoma.
Donaphine is the first large-scale Phase III clinical trial in the field of advanced hepatocellular carcinoma treatment in 12 years, with survival benefits and safety superior to that of soraphinists in large Phase III clinical trials.
the drug's domestic listing application was accepted by CDE in May 2020 and is expected to be approved in the second half of 2021.
, according to the China Cancer Registry, there were 400,000 new cases of liver cancer in China in 2018, accounting for 48% of the total number of new cases of liver cancer worldwide.
is the main subtype of liver cancer, accounting for about 90% of all liver cancer patients, with 360,000 new cases in 2018.
NO.2 avelumab first-line maintenance treatment of urethroid skin cancer Phase III JAVELIN Bladder 100 Research Company: Pfizer/Merck Drug Mechanism: PD-L1 monoantipressant chemotherapy is the current first-line standard treatment for patients with advanced bladder cancer, the initial response rate is high, but the probability of complete remission is low, most patients will be treated within 9 months of disease progression.
if bladder cancer metas metasse, the five-year survival rate is only 5%.
, chemotherapy delays the recurrence of the disease and prolongs the total survival of patients is an urgent need for clinical treatment in patients with advanced bladder cancer.
January 6, Pfizer/Merck Serrano announced that the Phase III JAVELIN Bladder 100 study had reached the primary endpoint of improving OS in its scheduled interim analysis.
THE JAVELIN Bladder 100 study included 700 patients with local late stage or metastatic urethroid skin cancer who did not progress from the initial treatment of induced chemotherapy, and random groups were given avelumab and optimal support therapy (BSC) as first-line maintenance therapy, or only BSC.
results found that patients in the avelumab-BSC treatment group had significantly longer lifetimes than those in the BSC-only group, and that this statistically significant difference was reflected in all patients and patients in the PD-L1-positive subgroup.
security results are consistent with previous studies and detailed data were presented at this year's ASCO conference.
results showed that patients who were randomly treated with avelumab-BSC (n-350) or BSC (n-350) had a medium follow-up time of 19.6 months and 19.2 months, respectively.
all randomized populations, Avelumab and BSC significantly improved patient OS (HR=0.69; P<0.001) compared to BSC;
PD-L1-positive subgroups, Avelumab and BSC also significantly extended OS (HR-0.56; P<0.001), with the two groups not reaching and 17.1 months, respectively.
in terms of secondary endpoints, based on an independent blinding center review, the medium PFS for avelumab and BSC vs BSC was 3.7 and 2.0 months(HR 0.62, 95% CI:0.) for all randomized populations, respectively. 52 to 0.75); In the PD-L1-positive subgroup, the two groups had a mid-PFS of 5.7 and 2.1 months (HR0.56, 95% CI: 0.43 to 0.73), respectively.
bladder cancer is the 10th most common tumor in the world, with about 500,000 new cases of bladder cancer diagnosed worldwide in 2018, and about 90 percent of bladder cancer in the United States, making bladder cancer a hotly contested area for PD-1/PD-L1 drugs.
T, O, I and K drugs were approved as second-line therapies for bladder cancer at the earliest, but in the competition for first-line therapies, or clinical failure, or uncertain prospects.
avelumab became the first first line of immunotherapy to successfully improve the total survival of patients with advanced urethra skin cancer.
NO.3 SAR442168 Therapeutic Multiple Sclerosis Phase II Research Company: Sanofi Drug Mechanism: BTK Inhibitors February 6, Sanofi announced that its BTK inhibitor SAR442168 Therapeutic Multiple Hair Ms Phase II Clinical Study (NCT03889639) reached its primary endpoint.
The IIb phase dose range study was designed with randomized, double-blind, placebo-controlled, cross-drug design, in which a group of patients (n-60) received 4 different doses of SAR442168 and were replaced with a placebo after 12 weeks of treatment for 4 weeks.
another group received a placebo treatment before receiving SAR442168.
group of patients (n-60) were treated with a placebo for 4 weeks before being replaced with SAR442168 to provide a dose-effect curve and simulate placebo exposure.
week 12 of the T1-enhanced T1 weighted imaging test results show that SAR442168 shows dose dependence in reducing the number of brain lesions in patients, and the safety of SAR442168 is consistent with previously published data, detailed data will be released at a medical conference in the near future.
the dose effect curve obtained in this Phase II study will provide the dose basis for the Phase III study of SAR442168.
Sanofi plans to evaluate the efficacy of SAR442168 in phase III studies in terms of MS recurrence frequency, disability progression, and central nervous damage, and related clinical trials for recurrence and progressive MS will start in the middle of the year.
, a chronic disease caused by abnormal attacks on the central nervous system by the body's immune system, is a high incidence in Europe and the United States, affecting about 1.2 million people.
Despite the significant improvement in MS treatment, about a third of patients with multiplex MS become more severely disabled over time, eventually developing advanced multiple sclerosis (PMS), which has few treatment options.
BTK is a popular target for the development of new drugs for B-cell malignant tumors, and the adaptive effects of BTK inhibitors are almost all concentrated in MCL, CLL/SLL and other B-cell blood tumors, and the development of treatment for MS is a new attempt, after only Merck evobrutinib completed the conceptual verification of the treatment of MS and entered Phase III research.
SAR442168 is the second conceptual validation study of oral highly selective BTK inhibitors for the treatment of multiple sclerosis (MS), and because of its strong blood-brain barrier penetration capability, phase I studies have also detected high levels of SAR442168 drugs in cerebrospinal fluid, which is expected to be the first treatment to improve brain damage in patients with relapsed MS.
NO.4 Gefapixant Treatment of Chronic Cough Phase III COUGH-1/COUGH-2 Research Company: Mercadon Drugs: P2X3 contagion antagonist Chronic Cough (cough duration lasts more than 8 weeks) Is approximately 10% globally among adults, but no new drugs have been approved to treat chronic cough, treatment needs are far from being met, and there are few projects to be developed worldwide to treat chronic cough.
March 17, Mercadon announced the first-line results of two key Phase III COUGH-1 and COUGH-2 studies for the treatment of incurable or unexplained chronic coughs by the P2X3 patient antagonist gefapixant.
two studies were conducted using international multi-center, randomized, double-blind, and placebo-controlled designs, and included 732 and 1317 patients with difficult to treat or chronic cough with unknown causes for coughing for more than one year, respectively.
two studies were randomly divided into three groups, including Gefapixant 45mg, 15mg and placebo, with the main endpoints of the study being the average number of coughs per hour over a 24-hour period during weeks 12 and 24, respectively.
COUGH-1 study's 12th and COUGH-2's 24th week results showed that Gefapixant 45 mg twice a day significantly reduced the number of coughs per hour compared to placebo, but in both studies Gefapixant 15 mg twice a day failed to reach the primary endpoint of the effect of reducing coughing.
the efficacy and safety of Gefapixant is consistent with the results of the Phase II study.
neuron hypersensitive after an injury or infection to the air, lungs, causing a persistent and frequent cough.
activation of P2X3 receptors is thought to be associated with hypersensitive sensory neurons.
Gefapixant, as a P2X3 subjecttag antagonist, has a clear effect on reducing the number of coughs and has completed a conceptual validation, and although a higher proportion of taste disorders have occurred in Phase II clinics, there is still a greater hope of becoming a new chronic cough drug for first in class with Phase III data.
Gefapixant is the first P2X3 antagonist to publish Phase III data and will also increase confidence in the development of other new drugs in the P2X3 class of antagonists.
NO.5 Tiragolumab first-line treatment PD-L1-positive non-small cell lung cancer Phase II CITYSCAPE Research Company: Roche Drug Mechanism: TIGIT inhibitor TIGIT is expressed in a variety of immune cells, including CD8-T cells, CD4-T cells and NK cells, is a CD226 co-stimulation receptor specific negative regulator.
CD155, which is highly expressed on the surface of tumor cells, is a high affinity liant for TIGIT, and once combined with TIGIT on the surface of NK and T cells, the killer effect of T cells on tumor cells is inhibited.
therefore, the double blocking of TIGIT and PD-1/PD-L1 theoretically relieves the inhibition of immune cells to a greater extent, allowing the immune system to play a stronger lethal role.
May 14, Roche presented detailed data from the PHASE II CITYSCAPE study of TIGIT single-anti-tiragolumab joint PD-L1 single-anti-Tecentriq first-line treatment of PD-L1-positive NSCLC patients in the form of oral reports at the ASCO2020 Conference.
135 EGFR-, ALK-, PD-L1-positive NSCLC patients were randomly grouped at 1:1 and given tiragolumab (600 mg), according to the CITYSCAPE study. q3w) - Tecentriq (1200mg, q3w) vs placebo (600mg, q3w) - Tecentriq (1200mg, q3w).
10.9-month follow-up results showed a significant improvement in Tiragolumab-Tecentriq treatment group ORR (37% vs 21%) compared to placebo-Tecentriq treatment group in ITT population, and a significant improvement (37% vs. 21%) in the PD-L1 high expression (TPS≥50%) population, compared to orr comfort in the Tiragolumab-Tecentriq treatment group (n-29) There was a significant increase in the dose of the drug, tecentriq (n-29), but in the PD-L1 low expression (TPS 1% to 49%), the tiragolumab-Tecentriq treatment group (n-38) orR did not improve compared to the placebo-tecentriq (n-39) (16% vs. 18%).
PFS, in the PD-L1 high-expression population, the survival benefits of the tiragolumab-Tecentriq treatment group were significantly higher than those of the placebo-Tecentriq (immature vs 4.11 months).
CITYSCAPE study provides conceptual validation data for the development of TIGIG monoantials, as well as the first effectiveness data obtained in the first-line treatment of lung cancer, and undoubtedly further direction for the development of TIGIG drugs for other players.
NO.6 ABBV-3373 Treatment of Rheumatoid Arthritis IIa Phase M16-560 Research Company: AbbVie Drug Mechanism: TNF-α Antibody Association Drug ABBV-3373 is ADC, consisting of adamo monoantigen and new glucosticoid regulator (GRM), can deliver the payload of glucosticoids directly to the active immune cells that express membrane binding to TNF, thereby regulating the inflammatory signaling path through which TNF is mediated.
ABBV-3373 is designed to precisely target the regulation of active immune cells, significantly reducing the systemic side effects associated with glucosal hormones, and is intended to be developed for the treatment of rheumatoid arthritis and other immuno-mediated diseases.
June 10, AbbVie announced the antibody-coupled drug ABBV-3373 to treat moderate to severe rheumatoid arthritis