Tumor control of new antibodies: Multiple PD-1/L1 monoanti-rebatch solid tumor new indications, ADC for cervical cancer to seek accelerated approval of the new observation of the medicine.

Nearly 100 authoritative leaders of domestic bio innovative drugs have spoken, hundreds of leading Biopharmaceutical Enterprises have paid close attention to it. More than 1000 pharmaceutical peers have signed up to participate. Dozens of innovative drug technologies have been collectively unveiled. Four hot biomedical fields, including tumor immunity, new antibodies, stem cell regenerative medicine, and gene therapy, are focused on. 2020 bpit The biopharmaceutical innovation technology conference will be held in Nanjing International Youth Cultural Center. From July 19 to 21, 2020, we will pay tribute to the next golden decade of innovative drugs and witness the new goals and new mileage of Chinese innovative drugs! This article is original and welcome to share. It must be authorized. July 5, 2020 / emedclub news / - - in recent years, PD-1 / L1, ADC and other new antibody strategies have been booming in the field of cancer treatment. A number of corresponding drugs have been approved and listed, which provides more treatment options and hope for some cancer patients.the expansion of the follow-up indications and the development of new products have also attracted much attention.this week, there are many new developments in the field of PD-1 / L1 and ADC.drug K was approved as the first-line treatment for colorectal cancer. Since its launch, keytruda (pembrolimzumab), a checkpoint inhibitor of mosartan, has been continuously approved for new indications, covering more than 10 cancer types and more than 20 indications.recently (June 29), FDA approved it for the first-line treatment of unresectable or metastatic microsatellite instability (MSI-H) or mismatch repair defect (dmmr) colorectal cancer (CRC).at the same time, keytruda is also the first PD-1 monotherapy approved for the first-line treatment of such patients.this approval is based on the results of a phase 3 trial, keynote-177, in which keyruda treatment significantly reduced the risk of disease progression or death by 40% and more than doubled the median progression free survival (PFS) (16.5 months vs. 8.2 months).in addition, the overall response rate (ORR) and complete response rate (CR) of keyruda group were 43.8% vs. 33.1% and 11.1% vs. 3.9%, respectively. The partial response rate (PR) was 32.7% vs. 29.2%.both MSI-H and dmmr tumors have abnormal effects on normal DNA repair.the frequency of MSI-H varies with different types and stages of cancer, but about 5% of patients with metastatic colorectal cancer are MSI-H or dmmr tumors.when the number of repeats of a short repetitive DNA sequence called microsatellite is different from that of DNA in healthy human cells, microsatellite instability may involve changes in DNA of cancer cells.MSI-H and dmmr have been approved successively in recent years as mature biomarkers for immunotherapy.in May 2017, keytruda was approved for the first time for posterior line treatment of MSI-H / dmmr pan solid tumors and colorectal cancer patients, which was also the first anti-tumor therapy approved by FDA, which was not based on tumor source but differentiated by biomarkers; in July 2017, opdivo was approved for posterior line treatment of MSI-H / dmmr colorectal cancer patients; in July 2018, opdivo + yervoy was approved for posterior line treatment of MSI-H / dmmr colorectal cancer R patients with colorectal cancer.drug B was approved again for urothelial cancer. On July 1, Merck / Pfizer announced that FDA had approved bavencio (avelumab, PD-L1 antibody) supplementary biological agent license application (SBLA) for the first-line maintenance treatment of locally advanced or metastatic urothelial carcinoma (UC). These patients did not progress after platinum containing chemotherapy.the press release states that this is the first-line immunotherapy to provide significant overall survival improvement in this patient population in phase 3 clinical trials.this approval is based on the results of a phase 3 clinical trial, javelin bladder 100 study, which showed that bavencio, as the first-line maintenance therapy combined with BSC, significantly improved the median overall survival (OS) by 7.1 months: 21.4 months vs. 14.3 months.the overall risk of death was reduced by 31%.Dr. Petros Grivas, one of the main researchers in the javelin bladder 100 trial, said: "avelumab is the first immunotherapy to show statistically significant improvement in overall survival in the first-line treatment of locally advanced or metastatic urothelial carcinoma, and FDA approval of avelumab is one of the most important advances in the treatment model in this field in 30 years.according to the randomized measurement, OS is more than 21 months, which is the longest overall survival period in phase 3 trials of advanced urothelial carcinoma. The javelin bladder 100 regimen with avelumab as the first-line conversion maintenance treatment may become a new standard treatment."urothelial carcinoma is the most common type of bladder cancer, accounting for 90% of the total number of bladder cancer patients, and bladder cancer is the 10th most common cancer in the world.in 2018, about 550000 people in the world were diagnosed with bladder cancer, with 200000 deaths; 82000 new cases and 38000 deaths in China.for patients with metastatic urothelial carcinoma who cannot be operated, the first-line treatment of platinum containing chemotherapy is relatively effective in the early stage, but when drug resistance leads to tumor recurrence and disease progression, the choice of treatment is very limited.in recent years, tumor immunotherapy has made a breakthrough. Several anti PD-1 / PD-L1 antibody drugs and ADC drugs have been approved by European and American countries for the second-line treatment of urothelial carcinoma.in May 2016, tecentriq was approved by FDA as a second-line treatment for adult patients with locally advanced or metastatic urothelial carcinoma who had previously received chemotherapy. It is suitable for patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or after treatment with platinum based chemotherapy or patients who received platinum chemotherapy before or after surgery for 12 months.became the first PD-L1 drug to be marketed in the world.on February 2, 2017, FDA approved the use of opdivo in patients with locally advanced or metastatic urothelial carcinoma who are resistant to platinum drugs. These patients have progressed during or after platinum based chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment of platinum based chemotherapy.on May 9, 2017, the FDA approved bavencio (avelumab, PD-L1) of Merck / Pfizer in Germany for locally advanced or metastatic urothelial carcinoma. It is suitable for patients with advanced or metastatic urothelial carcinoma treated with platinum containing drugs or with disease progression after treatment, or with neoadjuvant therapy or adjuvant platinum containing chemotherapy for patients with disease progression within 12 months.on May 18, 2017, FDA approved keyruda monotherapy for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma, who could not receive cisplatin chemotherapy.in addition, FDA also approved keyruda as a second-line treatment for locally advanced or metastatic urothelial carcinoma with disease progression during / after platinum containing chemotherapy or within 12 months of neoadjuvant / adjuvant platinum based chemotherapy.in May 2017, the FDA approved the use of imfinzi (durvalumab, PD-L1) for the treatment of locally advanced or metastatic urothelial carcinoma with disease progression during or after platinum containing chemotherapy or within 12 months after neoadjuvant or adjuvant treatment with platinum containing chemotherapy.on December 19, 2019, FDA accelerated the approval of padcev (enfortumab vedotin ejfv), an ADC drug jointly developed by Seattle genetics and Astellas, to be used in patients with locally advanced or metastatic urothelial carcinoma who have received PD-1 / L1 inhibitors and platinum based chemotherapy.padev is the first antibody drug conjugate approved for use in patients with this invasive disease.on July 2, Baiji Shenzhou announced that nmpa Drug Evaluation Center (CDE) had accepted the application for new indications (SNDA) of tirelizumab injection for the treatment of previously treated patients with unresectable hepatocellular carcinoma (HCC). this SNDA is based on the results of a key phase 2 clinical trial (nct03419897) for the treatment of previously treated patients with unresectable HCC. a total of 249 patients with unresectable HCC from 8 countries and regions in Asia and Europe were enrolled in this study. 138 patients had previously received one systemic therapy and 111 patients had received at least two treatments. patients received tiririzumab once every 3 weeks at a dose of 200mg. the primary endpoint of the trial was the objective response rate (ORR) assessed by the Independent Review Committee (IRC). ADC has positive clinical results in cervical cancer. On June 29, tisotumab vedotin, an innovative ADC drug jointly developed by Seattle genetics and genmab, achieved positive results in a potentially registered phase 2 clinical trial called innovatv204. at present, the orr of standard therapy for recurrent and / or metastatic cervical cancer is limited, usually less than 15%, and the median overall survival time ranges from 6.0 to 9.4 months. in the treatment of patients with recurrent or metastatic cervical cancer, the orr confirmed by independent center review was 24%, and the median duration of remission (DOR) was 8.3 months. the company will discuss with FDA to seek the possibility of obtaining accelerated approval based on this data. Seattle genetics is a pioneer in the field of ADC, and has cooperated to develop a number of approved ADC drugs. its main technology platform is used for the development of antibodies, linkers and small molecule toxins related to ADC drugs, as well as the structural modification of antibodies. It has licensed the technology to abbvie, Astellas, Bayer, celldex, Genentech, GlaxoSmithKline, Pfizer and Progenics, and cooperates with Takeda, Astellas, genmab and other companies. tisotumab vedotin is a kind of research ADC drug which targets tissue factor (TF) jointly developed by Seattle genetics and genmab. combines the anti TF antibody of genmab and the antibody coupling technology of Seattle genetics. tissue factor is highly expressed in cervical cancer, which can promote tumor growth, angiogenesis and cancer metastasis. recommended reading: ADC drugs have entered a period of rapid development, and the domestic market has been preempted. Who can stand out? recommended reading: ADC drugs have entered a period of rapid development, and the domestic market has been preempted. Who can stand out Biopharmaceutical innovation technology conference will be held in Nanjing International Youth Cultural Center. at that time, many experts and scholars in the industry will bring more information on the research and development progress, innovative technology and future development direction of new antibody drugs in the sub forum of the third international new antibody drug development summit forum. let's wait and see! Click the picture above to view the agenda of the conference