Broadly defined tumor immunotherapy first began in 1893, and immune-related drugs such as interleukin-2 and interferon were used for tumor treatment before the advent of PD-1/PD-L1 inhibitors.
In 1987, American scholar Jim Allison discovered CTLA-4; in 1989, Israeli scholar Zelig Eshhar developed the first generation of CAR-T cells; in 1992, Japanese scholar Tasuku Honjo discovered PD-1; and in 1999, Chinese-American scholar Zhen Zhen Ping discovered PD-L1. The first generation of CAR-T cells were developed by Tasuku Honjo in 1992; PD-1 was discovered by Tasuku Honjo in 1992; and PD-L1 was discovered by Chen Ping, a Chinese-American scholar, in 1999.
For any new drug to come to market, there are 3 steps: basic research, animal studies, and human trials. The first step in the process is the development of a new drug, which will be validated in Phase I-III human trials before it is officially launched. The Phase I trial is to observe the tolerance and pharmacokinetics (safety assessment) of the new drug; the Phase II trial is to evaluate the efficacy of the drug; and the Phase III trial is to confirm the efficacy and safety of the drug and to test the optimal dose of the new drug, which ultimately provides sufficient evidence for the registration review of the drug. In addition, after a new drug is launched, a phase IV clinical trial is conducted to examine the efficacy and adverse effects of the drug under widespread use conditions.
The 5 PD-1/PD-L1 inhibitors that have been approved by the US FDA and their indications have clear data from human trials. Therefore, the use of these drugs in the indication is not a “trial drug”, let alone a “guinea pig”. The drugs that are marketed abroad will need to be tested in clinical trials in Chinese patients to further validate safety and efficacy before they are introduced into China.
Co-reviewed by: Guangdong Provincial People’s Hospital, Guangdong Lung Cancer Research Institute, Dr. Wang Zhen Linlin Li