The Combination of PD-1 mAb and Atinumab

Posted by beauty33 on January 29th, 2021

Recently, Hengrui Medicine issued an announcement that its anti-PD-1 antibody SHR-1210 combined with atinumab mesylate in the first-line international multi-center phase III clinical trial of hepatocellular carcinoma has been communicated with the US FDA, and the trial is about to be launched in the US , Europe and China simultaneously.

It is reported that the content of the communication between the two parties involves the overall design of the phase III clinical trial program, patient selection, primary endpoints, secondary endpoints, efficacy evaluation, statistical analysis methods and related details. The FDA agrees that the upcoming phase III clinical trials are ok if the results of the mid-term analysis of the progression survival period meet the preset statistical standards, the production will be declared in advance. If the application is finally passed, it will be accelerated by the FDA.

SHR-1210 is a humanized anti-PD-1 antibody independently developed by Hengrui Medicine, which can be used for the treatment of hematological malignancies and solid tumors. On April 23, Hengrui submitted a listing application for the treatment of SHR-1210 classic Hodgkin lymphoma (cHL), which has been accepted by CDE and has been included in the priority review. It is expected to become a domestic classic Hodgkin lymphoma (cHL). The first domestic marketed product in the therapeutic field. Apatinib is a small molecule anti-angiogenic tyrosine kinase inhibitor targeting VEGFR-2. It was approved for marketing in China in October 2014 under the trade name Aitan.

Currently, therapies for liver cancer are very limited. The objective response rate (ORR) and median progression-free survival (mPFS) of the second-line treatment drug Regofinil for liver cancer patients were 11% and 3.1 months, respectively. In contrast, the results of a phase I b study published in the Journal of Clinical Oncology in October 2018 showed that the objective response rate (ORR) of SHR-1210 combined with apatinib mesylate for the treatment of advanced hepatocellular carcinoma ) Up to 50%, the median progression-free survival (mPFS) reached 7.2 months, and the 6-week disease control rate reached 93.8%. The curative effect was significantly better than the current standard treatment.

In addition, in terms of safety, the side effects of the combined use of SHR-1210 and apatinib are similar to those of the single use, mainly hypertension and elevated transaminases. With excellent clinical data, SHR-1210 combined with apatinib has the potential to become a first-line treatment for liver cancer.


Apatinib is the first VEGFR-2 oral small molecule tyrosine kinase inhibitor successfully applied to gastric cancer. It was originally synthesized and patented by Advenchen Labs, and its foreign name was Rivoceranib (Apatinib, YN968D1). Hengrui Medicine obtained the right to develop in China in 2005, and LSK BioPharma obtained the right to develop the drug globally except in China.

In October 2014, apatinib was approved for marketing in China under the trade name Aitan. It is used for patients with advanced gastric adenocarcinoma or gastric-esophageal junction adenocarcinoma who have progressed or recurred after receiving at least two systems of chemotherapy in the past; At the same time, preliminary results have been achieved in clinical exploration of many other tumor types, including advanced or metastatic gastric cancer and colorectal cancer.

In October 2018, Hengrui Medicine and LSK BioPharma, a US biotechnology company, reached an agreement to jointly carry out global clinical cooperation, which will jointly develop PD-1 monoclonal antibody Carrelizol (SHR-1210) and LSK's VEGFR-2 inhibitor Apatinib is used in combination for the treatment of hepatocellular carcinoma. Hengrui will be responsible for related clinical trials in this cooperation, and all research expenses outside of China will be divided equally between the two companies.

Multiple indications are under development

At present, anti-angiogenesis therapy and PD-1/PD-L1 monoclonal antibody combination therapy have achieved important breakthroughs. By blocking the VEGF pathway, blood vessels can be normalized, and lymphocytes can be transmitted to the tumor site more and Tregs can be reduced. The expression of immune negative feedback cells such as TAM and TAM is beneficial to improve the immune microenvironment of tumors, and the response rate to solid tumor combination therapy has generally been improved to varying degrees.

Hengrui Medicine's PD-1 monoclonal antibody SHR-1210 combined with apatinib has completed the clinical phase I dose exploration trial. From the experimental data, the response rate of the combined drug for gastric cancer, liver cancer, and lung cancer is relative to that of PD-1 single Drug reference data have been improved to varying degrees. At the ASCO2018 meeting, the objective response rate and disease control rate of SHR-1210 combined with apatinib for the treatment of patients with advanced liver cancer were 50.0% and 85.7%, respectively. At the same time, SHR-1210 is unique. The incidence of side effects of capillary hemangioma is greatly reduced after the combination.

According to reports, Hengrui Medicine SHR-1210 combined with apatinib has a good synergistic effect. The phase II clinical trial of the combined drug involves a variety of indications, including non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, and soft tissue sarcoma.

Like it? Share it!


About the Author

Joined: July 10th, 2017
Articles Posted: 286

More by this author