2021 CSCO Professor Sheng Xinan: Immunization combined with ADC, a new breakthrough in the treatment of metastatic urothelial cancer

Introduction Urothelial carcinoma is a common malignant tumor in the world, and it is also one of the common malignant tumors of the urinary system in China
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With the rapid development of basic immunology and tumor biology in recent years, its treatment model is constantly changing
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During the 2021 CSCO meeting, Yimaitong had the honor to interview Professor Sheng Xinan from Peking University Cancer Hospital to introduce us to the research progress in the treatment of metastatic urothelial cancer
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Expert Profile Professor Sheng Xinan, Chief Physician, Associate Professor, and Doctoral Supervisor, Deputy Director, Department of Urology and Oncology, Peking University Cancer Hospital, China Society of Clinical Oncology (CSCO) Council Member, CSCO Youth Expert Committee Standing Committee Secretary, CSCO Renal Cancer Expert Committee Standing Committee Member, CSCO Urothelial Cancer Expert Committee Standing Committee Executive Director of the Youth Council of the Cancer Society Member of the Renal Cancer Group of the Urological Oncology Committee of the Chinese Anti-Cancer Association Member of the Oncology Group of the Youth Committee of the Urology Branch of the Chinese Medical Association Deputy Leader of the Oncology Group of the Youth Committee of the Chinese Medical Association Yi Maitong, deputy head of the Urology Group of the Rare Disease Branch of the Medical Association: Urothelial cancer is a more common type of advanced urinary tumors.
Could you please introduce the current status of diagnosis and treatment of urothelial cancer? Professor Sheng Xinan: The tissue sources of urothelial cancer are different.
Among them, bladder-derived tumors are the most common, which is commonly referred to as bladder cancer in the past.
It is collectively referred to as urine with renal pelvis, ureter and other upper urothelial tumors.
Carcinoma of the epithelium
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Different tumor sources have different treatment methods
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Urothelial carcinoma tends to have hematuria symptoms in the early stage, and it is easier to be found in the early stage.
For this kind of early stage tumor, surgery is usually chosen
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However, muscular invasive urothelial carcinoma is prone to recurrence and distant metastasis, and its treatment is a hot topic of clinical concern
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In recent years, we have made a lot of progress in the treatment of metastatic urothelial carcinoma, especially in the application of new drugs.
From PD-1/PD-L1 monoclonal antibody-based immunotherapy, we have successively developed inhibitors against FGFR mutations.
And antibody-drug conjugates (ADC) and other new biological targeted drugs
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While new drugs continue to emerge, the treatment model for urothelial cancer is also constantly changing
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Of course, for advanced patients, traditional platinum-based chemotherapy is the mainstay, and immunotherapy may be the first choice for post-line treatment
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At present, sequential immunotherapy has become the first-line treatment for advanced urothelial cancer
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In recent years, many researches on immune combination therapy have also been carried out.
At present, it is difficult to make greater breakthroughs in research related to chemotherapy combined treatment strategies, and the data of immune combined ADC initially shows a good synergistic effect, so the future immune combined ADC will be Important development trends may change the treatment of advanced urothelial carcinoma in recent years
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In addition, immunotherapy has also moved forward to adjuvant therapy and neoadjuvant therapy.
For high-risk muscular invasive urothelial carcinoma, immunotherapy can prevent recurrence and metastasis.
Combination therapy strategies centered on immunotherapy are also applied to neoadjuvant therapy.

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Yimaitong: At this year’s CSCO meeting, you reported a Phase 1B/II clinical study on the safety and effectiveness of vedicitumumab combined with teriprizumab in the treatment of patients with locally advanced or metastatic urothelial cancer Please introduce the latest data of this study.
What clinical significance does this study have for the diagnosis and treatment of urothelial carcinoma? Prof.
Sheng Xinan: Immunization combined with ADC is an important research direction in the treatment of advanced urothelial cancer.
Vidicuzumab is an ADC drug originally developed for HER2 in China
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Under the leadership of Director Guo Jun, we have successively carried out two phase II clinical studies, one of which is a multi-center phase II clinical study using vedicitumumab for locally advanced or metastatic HER2-positive urothelium that has failed conventional treatment.
Cancer patients
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The results of the study showed that the objective response rate (ORR) of vedicitumumab in such patients could reach 50%-51.
2%, the median progression-free survival (PFS) reached 6.
9 months, and the overall survival (OS) ) Reached 14.
2 months
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Patients who have failed conventional treatment, especially chemotherapy, often have a poor prognosis, and the treatment options available are also very limited.
The often-mentioned immunotherapy is only effective in some patients who are sensitive to immunotherapy, and there are still many patients who are immune to immunotherapy.
It is not sensitive, its overall ORR is only about 20%, and the median PFS is only 2-3 months
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ADC can greatly improve the efficacy of such patients, and accurately screen out HER2-positive patients, which is a major breakthrough
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At this CSCO meeting, we reported the preliminary efficacy of vedicitumumab combined with teriprizumab in the treatment of patients with locally advanced or metastatic urothelial cancer
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At present, the study has enrolled 25 patients, including patients with metastatic urothelial carcinoma who were newly treated and failed multi-line treatment
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There are no special restrictions on whether they are HER2 positive or PD-L1 positive .

In this context, it can still be observed that the overall ORR has reached 75%, which is significantly improved compared to traditional first- and second-line treatments
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Next, we will complete the enrollment and observe the patient's PFS and the duration of the effect
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At the same time, based on the preliminary good data of this study, we may next carry out a phase III clinical study of vedicitumumab combined with teriprizumab for the first-line treatment of advanced urothelial cancer
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In addition, the combined program may also move forward to the field of neoadjuvant therapy.
These explorations will further consolidate the advantages of vedicitumumab in the field of anti-HER2 therapy for urothelial cancer
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At present, in the field of urothelial cancer anti-HER2 treatment, we are still at the forefront of the world.
The combination of immunotherapy and ADC is an important direction.
We look forward to the follow-up research results and hope that more patients can join this Clinical studies
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Yimaitong: What other directions are worth exploring for ADC in the future? Professor Sheng Xinan: The combination of ADC and immunotherapy may move forward in the future, including the aforementioned exploration for neoadjuvant therapy
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In the current research, whether immunotherapy is combined with vedicitumumab or with Enfortumab vedotin (EV), the ORR can reach 70%-80%.
We expect this combined strategy to move forward to neoadjuvant therapy At this stage, the pathological complete remission rate of patients will be improved, so that more patients will benefit
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