2020 Karelli Pearl Single Resistance Summary Report

As a PD-1 inhibitor independently developed by Hengrui Pharmaceuticals, Karelli pearl monoantigen is a humanized IgG4 monoantigen, antibody-dependent cell-mediated cytoxic action (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP) and complement-dependent cytoxicity (CDC), which can effectively reduce T-cell depletion and help to play a sustained tumor suppression effect.
Preclinical in vitro and in vivo experiments showed that karelli bead monoantigen had a unique binding table, affinity and drug ability, high occupancy of PD-1 receptors in the body, and long-lasting time, the 22nd day of possession is still >95%, its IC50 and EC50 lower, 0.7nM and 0.38nM, respectively, to promote the release of T cells IFN.
is properly distributed in the body, the half-life is short, only 5.5 days, can achieve rapid drug removal, safety and tolerance is better1.
Since 2015, Karelli Pearl Monoanti has conducted a series of phase I-III clinical studies at home and abroad to treat a variety of malignant tumors, and in May 2019 NMPA was approved for relapse or refragsive classic Hodgkin's lymphoma treatment with at least 2-line system chemotherapy.
, Karelli's single resistance "opened up" all the way.
in 2020, has been approved liver cancer, esophageal cancer, lung cancer related to the field of adaptive disorders, is currently the most adaptive domestic PD-1 single resistance.
Figure 1 Karelliju single anti-adhesive disease approval process in 2020, in addition to the approval of 3 adaptive diseases, Karelli pearl single resistance in the research progress has also been a bumper harvest, in liver cancer, ovarian cancer, stomach cancer, nasopharyngeal cancer, cervical cancer and other fields have important research data published.
February of this year, a study led by Professor Qin Shuxuan on the treatment of advanced hepatocellular carcinoma with a single anti-monotherapy drug was the first to log on to The Lancet Oncology, with an objective remission rate of 14.7% and an estimated six-month total survival rate of 74.4%.2.
Then, in May, the ESCORT study led by Professor Huang Mirror on the treatment of advanced or metastatic esophageal squamous cancer, led by Professor Karelli Pearl, was again published on The Lancet Oncology, with a neutral survival time of 8.3 months3.
at the subsequent annual meetings of ASCO and ESMO, Karelli's single-drug resistance was announced, and a number of studies on single-drug or combined therapy were selected for the conference report.
October this year, the CLAP study led by Professor Huang Xin published data on the treatment of patients with advanced cervical cancer with a 55.6 per cent ORR at Journal of Clinical Oncology.
November, professor Wang Jie led the PASSION study, published in Journal of Thoracic Oncology, which provides new evidence of immune co-targeting (Carelli's beadone and apatinib) for the second-line treatment of broad-stage small cell lung cancer5.
, carelli-pearl monoantigen, provided a large group of data for immunotherapy Chinese a variety of malignant tumors (Table 1).
2020 main study data, CameL study 12 once again captured the eye, the full study was published online on December 19, 2020 in The LANCET Health Medicine (IF 25.094).
the study included 412 patients with advanced non-squamous non-small cell lung cancer (NSCLC) with EGFR or ALC mutation-negative, 1:1 random acceptance of Karelli pearl monoantigen anti-combination chemotherapy (Karelli pearl monoantigen anti-combination pygmy After 4-6 cycles of treatment in the plug and carptin, trial group) or chemotherapy (Peme curvature and carpton, control group), the treatment was maintained with pyrethroids±
patients with disease progression in the control group were allowed to receive carelliju monodrectotherapy, but carellidul monoantitherapy did not last more than 2 years (Figure 2).
2 CameL study design based on the results assessed by the Independent Centre for Blind Law Review Committee (BICR), the medium non-progression lifetime (mPFS) in the pilot and control groups was 11.3 months (95% CI 9.6 - 15.4) and 8.3 months (95% CI 6.0-9.7) (HR=0.60, p=0.0001, Figure 3).
12-month PFS rate was 49.6 per cent (41.7 per cent - 57.1 per cent) and 35.1 per cent (27.0 per cent - 43.2 per cent) respectively.
PFS subgroup analysis also showed that the efficacy of the trial group was better than that of the control group at all subgroup levels.
as of February 25, 2020, the medium follow-up time was 19.3 months, the control group had a mid-OS of 20.5 months, and the pilot group's mid-OS had not yet been reached, and the forecast could reach 27.9 months (HR=0.73, p=0.0117).
for patients with PD-L1 expression levels ≥1%, the medium PFS in the trial and control groups was 15.4 months and 9.9 months, respectively (HR=0.56, p=0.0011).
PFS subgroup analysis also showed that the efficacy of the experimental group was better than that of the pure chemotherapy group at all subgroup levels.
(124/205) and 38.6% (ORR) were 60.5% (124/205) respectively in the progress-free lifetime (PFS) trial group and control group assessed in Figure 3 BICR (80/207), p<0.0001;
duration (DoR) was 17.6 months and 9.9 months, respectively, and the duration of disease relief (TTR) was 1.5 months and 2.7 months, respectively.
safety, the rates of adverse events (TRAEs≥ associated with level 3 therapy in the trial and control groups were 69% and 47%, respectively.
most common immuno-related adverse events (irAEs) include reactive skin capillary hyperpluration (RCCEP, 78%), elevated alanine transaminase (12%), elevated tyrosteine transaminase (11%) and hypothyroidism (10%).
77% of patients with RCCEP were 1/2 and only 2 patients with level 3 RCCEP were 1/1%.
In all the published NSCLC First-Line Treatment Important Phase III studies, the higher ORR, longer PFS, and OS obtained by the Carelli Juju mono-anti-combination chemotherapy program demonstrated by the CameL Institute has also been written into the 2020 CSCO guidelines as a phase IV non-scale NSCLC first-line recommended treatment, bringing more hope of cure for patients with late-stage metastasis NSCLC in China.
2020 is just the beginning of the Karelli Pearl Single Resistance Journey, and there are many more data and surprises waiting for us in the future.
At present, the application for adaptation to the first-line treatment of advanced nasopharyngeal cancer by kariliju single-cell chemotherapy has been included in the priority review by the Drug Review Center of the State Drug Administration, while the two Phase III studies of Karelli-Pearl single-cell chemotherapy first-line treatment of advanced squamous non-small cell lung cancer and esophageal squamous cancer have reached the main research end and will be submitted for listing in the near future.
the treatment of advanced cervical cancer with the second-line treatment of the new carellidala monoantigen anti-combination drug, Famini, has also been made public by CDE in the breakthrough treatment varieties.
look forward to more data on Karelli's monoantigen in the future, and hope that Karelli's single resistance will bring more benefits to the clinic for the benefit of more cancer patients.
: 1. Expert Committee on Anti-Oncology Drug Safety Management of the Chinese Society of Clinical Oncology and Expert Committee on Immunotherapy of the Chinese Society of Clinical Oncology. Consensus of Experts in clinical diagnosis and treatment of Carelli's single anti-reactive skin capillaries, Journal of Clinical Oncology, 2020, 25 (9): 840-848.2.Qin S, Ren Z, Meng Z, Chen Z, Chai X, Xiong J, Bai Y, Yang L, Zhu H, Fang W, Lin X, Chen X, Li E, Wang L, Chen C, Zou J. Camrelizumab in patients with patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, Lancet Oncol. 2020 Apr; 21(4):571-580.3.Huang J, Xu J, Chen Y, Zhuang W, Zhang Y, Chen Z, Chen J, Zhang H, Niu Z, Fan Q, Lin L, Gu K, Liu Y, Ba Y, Miao Z, Jiang X, Zeng M, Chen J, Fu Z, Gan L, Wang J, Zhan X, Liu T, Li Z, Shen L, Shu Y, Zhang T, Yang Q, Zou J; ESCORT Study Group. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020 Jun; 21(6):832-842.4.Lan C, Shen J, Wang Y, Li J, Liu Z, He M, Cao X, Ling J, Huang J, Zheng M, Zou G, Yan H, Liu Q, Yang F, Wei W, Deng Y, Xiong Y, Huang X. Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial. J Clin Oncol. 2020 Dec 1; 38(34):4095-4106.5.Fan Y, Zhao J, Wang Q, Huang D, Li X, Chen J, Fang Y, Duan J, Zhou C, Hu Y, Yang H, Hu Y, Zhou J, Lin X, Wang L, Wang Z, Xu Y, Zhang T, Shi W, Zou J, Wang J. Camrelizumab Plus Apatinib in Extensive-Stage SCLC (PASSION): A Multicenter, Two-Stage, Phase 2 Trial. J Thorac Oncol. 2020 Nov 6:S1556-0864(20)30806-6.6.Chen X , Wu X , Wu H , et al. SHR-1210 combined with GEMOX as first-line treatment in patients with advanced biliary tract cancer. Journal of Clinical Oncology, 2020, 38(4_suppl):535-535.7.Wu XH, Xia LF, Zhang YZ, et al. Famitinib malate plus camrelizumab in patients with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: a multicenter, open-label, single-arm, phase II trial. SGO 20208.Liu Y , Han G , Li H , et al. Camrelizumab combined with FOLFOX as neoadjuvant therapy for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma. Journal of Clinical Oncology, 2020, 38(15_suppl):4536-4536.9.Wang J , Zhang Z , Yan X , et al. Efficacy and safety of SHR-1210 combined with apatinib in first-line treatment for advanced lung s。