[2022 WCLC] Professor Fan Yun | Schwotinib has another international academic stage, EGFR No. 20 outer appetite insertion of mutant -variable late NSCLC precision targeted therapy for future promotion is expected!

*For medical professionals for reading reference

introduction:

As one of the annual festivals in the field of lung cancer, after two years of pure virtual forms in the World Lingcium Cancer Conference (WCLC), it was held in the form of offline+online in Vienna, Austria from August 6th to 9th, 2022. In this conference, the first and only national innovation medicines in the field of lung cancer, the only "breakthrough therapy identification" of China and the United States -Schwotinib once again appeared on the international academic stage and announced the latest data: on the RP2D dose (300 Under mg, QD), Schwotinib for the treatment of previous chemotherapy failure EGFR 20 outer appetite plugged into the late -changing late NSCLC patients, the objective relief rate (ORR) is as high as 52.4%. And in a variety of mutation subtypes, the curative effect is displayed, the overall security is good, and the research results are encouraged. On the occasion of this event, Professor Fan Yun in the medical community invited Professor Fan Yun in the Cancer Hospital of the Chinese Academy of Sciences to update the data to update the data, and look forward to the new direction of diagnosis and treatment in the field of EGFR 20 outer slogan insertion.

Study introduction

As a oral high -selective EGFR tyrosine kinase inhibitor with a multi -selective EGFR tyrosine kinase inhibitor, with its excellent curative effect and safety, it has become the first and the only two in the field of lung cancer with excellent efficacy and safety. The "Class I New Drug" of the "Breakthrough therapy" of the country has been carried out globally globally. The data reported at this WCLC conference comes from the summary analysis of the three multi-centered clinical research (WU-KOong1, Wu-kong2, and Wu-Kong6 of Schwotinib at home and abroad. The study design is based on the design design as shown in Figure 1).

Figure 1: WU-KONG1, WU-KONG2, and Wu-Kong6 research design; WU-KOong1 research as international multi-center research, covering countries and regions such as the United States, Australia, South Korea, Japan, and Taiwan; All China Multi -Center Studies

Main research results

As of April 30, 2022, a total of 119 patients with chemotherapy failed, and the EGFR EXON20INS mutated late NSCLC patients were included in the efficacy analysis set (baseline features are shown in Table 1). Research results: 84 patients who were treated with Schwotinib RP2D dose (300mg QD) treatment, ORR was as high as 52.4%(as shown in Table 2); the proportion of patients with brain metastases was as high as 31.1%. Patients with brain metastases also show a good anti -tumor activity, and ORR reaches 44%(see Figure 2).

Table 1: Effect analysis set (n = 119) patient baseline features; BM: Brain Metastasis, brain metastases;#1 patient (1.2%) data disappear lost

Figure 2: The best percentage of the size of the target lesion; AMI: amivantamab; BM: Brain Metastasis, brain metastases

Table 2: Schwotini has anti -tumor activity of patients with EGFR EXON20INS mutations and late -stage NSCLC for the failure of chemotherapy. Disease stable; PD: disease progress

It is particularly noteworthy that 119 patients who were incorporated into the efficacy analysis this time, there are about 30 types of EGFR EXON20INS mutations. Regardless of the position of inserting mutations, multiple mutant subtype patients can be treated from Schwotinib for treatment from the treatment of Schwotini Interest benefits: 82 patients inserted mutations occurred at the Near-Loop, Orr reached 52.4%, and the disease control rate (DCR) reached 89%; 29 patients inserted the mutation position at the far-loop (Far-Loop ), Orr reached 41.4%, and DCR reached 86.2%(see Figure 3).

Figure 3: Schwotini for different EGFR EXON20INS mutations subcontments of anti -tumor activity

By the deadline of the data (April 30, 2022), a total of 238 patients with EGFR or HER2 mutations were included in the set of safety analysis. The security data matured further than the advance. Common types of adverse reactions are similar to traditional EGFR-TKI, mainly diarrhea and rash, and most of them are level 1-2 adverse reactions (as shown in Table 3), which can be managed and restored in clinical clinical.

Table 3: Drug -related adverse reactions (≥3) summary table of the occurrence rate of Schwotinib incidence rate ≥10%

Expert Reviews

EGFR No. 20 outer sub-appeal mutation will change the structure of EGFR protein "ɑC-spiral" and "c-spiral (ie, phosphate binding ring, P-ring)" (see Figure 4) The smaller pockets lead to the combination mode and affinity of EGFR 20 outer sub-insertion and wild-type EGFR, which reduces the selectivity of the traditional 1-3 generation EGFR-TKI. Therefore, patients carrying mutations with EGFR 20 outer appendes are not sensitive to the traditional 1-3 generation EGFR-TKIS treatment. Nevertheless, patients with EGFR 20 appetizer have similar clinical features of EGFR mutations, that is, the low tumor mutation load is low, resulting in poor tumor immunogenicity and low sensitivity to immunotherapy [1-2]. Previous studies have shown that traditional EGFR-TKIS, immunotherapy and chemotherapy are used for EGFR 20 exogenous appetizers to insert a variant of late NSCLC or less than 20%, and the median survival period is less than 17 months. 5], cannot meet the patient's clinical treatment needs, so it is urgent to develop new drugs that are more effective and safe and tolerant to this disease.

Figure 4: Amino acid coded by EGFR 20 outer appende

Regardless of the mutation position, Schwotini shows good anti -tumor activity on different EGFR EXON20INS mutations subcontments

Due to the large change of the position and size of the inserting mutation, the variant of the EGFR 20 out -of -reveal subsequent sub -insertion has a strong variant and a large number of subtypes. About 90%of the mutation subtypes occur on the ring after "C-Spiral" [6], and the insert mutation of insertion on the "C-Spi" is divided into "near-ring insertion mutations" and "far ring" Connectal mutation "[7]. Different variants are inserted. The patient's sensitivity to EGFR-TKI is not completely consistent. Some research results have prompting: "Nearly ring insertion mutations" is significantly better than "distant ring insertion mutations" (ORR " : 46% vs 0%, P = 0.0015) [8]. However, judging from the update data reported at this WCLC conference, regardless of the insertion of the mutation position, Schwotini shows good anti -tumor activity for different EGFR EXON20INS mutations subcontments: "close -ring insertion mutation" ORR reached 52.4%, and 52.4%, which is 52.4%. "Far ring insertion mutation" ORR reached 41.4%.

Schwotinib brings new hope for patients with EGFR EXON20INS mutations subcontracted brain metastases

As one of the common metastasis parts of lung cancer, about 23%-39%of EGFR 20 exterior appetite inserted mutant NSCLC patients have brain metastases in the early stages of treatment [9]. Such patients often have poor prognosis and quality of life. Equipment. Although radiotherapy can alleviate the symptoms of the nervous system of patients with brain metastases, it cannot effectively extend the OS, and it may also reduce the quality of life and damage. Although new drugs that have been targeted for EGFR 20 have been listed overseas in recent years, their curative effect requires a large samples III clinical trial verification, and the efficacy of these new drugs on brain metastases is still limited. Orr is only 18% of 18% [10]. Summary analysis of the Schwotinib, WU-KONG2, and WU-KONG6, which was reported at the WCLC conference this time: Schwotinib the treatment base line with EGFR EXON20INS mutant patients with a brain metastases of 44%, the result is 44%, and the result Surprising. In addition, the overall tolerance of Schwotinib is good, the types of adverse reactions are similar to the traditional EGFR-TKI, and there are no special adverse reactions, and most of them are level 1-2, which can be managed and restored in clinical practice. This also means that Schwotini patients with EGFR EXON20INS mutant -variable late NSCLC patients who are accompanied by brain metastases have also taken good on good safety while improving the activity of anti -tumor.

Conclusion

As a high-selective EGFR-TKI, which is independently developed by Dazhe Pharmaceutical, oral, irreversible suppression, and targeting multiple EGFR mutations subcontrays, it has repeatedly appeared on the international academic stage with excellent research data. At present, there are many key clinical studies in simultaneous development at home and abroad. I look forward to the announcement of more research results in Schwotinib and benefit patients with global patients as soon as possible!

Expert Introduction

Professor Fan Yun

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

Director of the Department of Internal Medicine of the Chest, Chief Physician, Bo Director

Director of China Clinical Oncology Society

Deputy Chairman of the China Clinical Oncology Society of Small cell lung cancer expert committee

Deputy Chairman of the Education Expert Committee of the China Clinical Oncology Society

Standing Committee Member of the Chinese Physician Association Cancer Multi -Disciplinary Diagnosis and Treatment Committee

Chairman of the Zhejiang Anti -Cancer Association Cancer Internal Medicine Committee

Chairman of the Zhejiang Medical Association Cancer Precision Treatment Committee

Deputy Chairman of the Cancer Branch of Zhejiang Medical Association

references:

[1] .Geng d, et al. Clin Transl Oncol, 2022 Feb; 24 (2): 379-387.

[2] .friedlander a, et al. Nat Rev Clin oncol. 2022 Jan; 19 (1): 51-69. [3] .Yang G, et al. LUNG CANCER. 2020 jul; 145: 186-194.

[4] .dimitrios tomaras, et al. 2020 esmo. Abstract #1362p.

[5] .bazhenova l, et al. LUNG CANCER. 2021 DEC; 162: 154-161.

[6] .vyse s, et al. Signal transduct target theer, 2019,4: 5

[7] .jacqulyne P. Robichaux, et al. Nature (2021) .597: 732-737

[8] .yasir y. elamin, et al. Cancer cell, 2022, 40: 754-767

[9] .remon j, et al. CANCER TREAT Rev. 2020 nov; 90: 102105.

[10]. Pasi a j .nne, et al. 2022 asco

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