7. Immunotherapies are so new, is the research evidence on them strong? Will we be the “guinea pigs”?
.
Broadly speaking, tumor immunotherapy first started in 1893, and immune-related drugs such as interleukin-2 and interferon were used for tumor treatment before PD-1/PD-L1 inhibitors became available.
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. After that, along with the discovery of PD-L1 with 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 three steps: basic research, animal studies, and human trials. The company’s main goal is to provide a comprehensive range of products and services to the market. The Phase I trial observes the tolerance and pharmacokinetics (safety assessment) of the new drug in humans; the Phase II trial evaluates the efficacy of the drug; 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 application. 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 five PD-1/PD-L1 inhibitors that have been approved by the US FDA and their indications have clear data from human trials. The newest and most recent version of the drug is a new version of the drug that has been approved by the FDA. 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.
8. Most of the clinical trials of PD-1/PD-L1 inhibitors have been conducted abroad, can the efficacy and safety data be extrapolated to the Chinese?
.
Due to differences in pharmacokinetics (different rates of drug metabolism) and pharmacodynamics (different starting doses and maximum tolerated doses), differences in efficacy, safety, dose, and dosing regimens may occur between patients of different ethnicities for the same drug. Based on safety considerations, it is stipulated in the Drug Registration Administration that foreign-marketed drugs need to be subject to clinical studies in Chinese patients before entering China.
Among the four PD-1/PD-L1 inhibitors that have been approved by the FDA for NSCLC treatment, Nivolumab has been the first to obtain efficacy data in Chinese patients – the CHECKMATE078 study. The study enrolled only East Asian populations (especially Chinese) and found that nivolumab reduced the risk of disease progression by 23% compared to chemotherapy and was more effective in patients with squamous cancer. Smoking is the leading cause of lung cancer in China, and adenocarcinoma is much less common among patients who smoke. nivolumab’s better results in squamous cancer may be good news for patients in China.
Studies of Pembrolizumab, Atezolizumab, and Durvalumab enrolling Chinese lung cancer patients (including IMPOWER 133, IMPOWER010, NCT02273375, KEYNOTE032, and more than a dozen other studies) are ongoing, and their results will answer our common questions –The results of these studies will answer the common question of whether the introduction of PD-1/PD-L1 inhibitors into our country will be “uncomfortable”.
9.
9. Where can I get access to clinical trials? What clinical trials are being recruited in China?
.
The main PD-1/PD-L1 inhibitors approved by the US FDA for NSCLC are Pembrolizumab (made by Merck Sharp & Dohme), Nivolumab (made by Bristol-Myers Squibb), Atezolizumab (made by Roche), Durvalumab (made by AstraZeneca), and all currently have studies recruiting Chinese patients are underway.
In addition, studies are underway with domestic PD-1/PD-L1 inhibitors (none of which have been approved for marketing) made by Cinda Biologics, Hengrui Pharmaceuticals, Baxi Shenzhou, Junshi Biologics, and Zhengda Tianqing.
The following table summarizes the PD-1/PD-L1 inhibitor clinical trials currently underway that include patients with NSCLC and small cell lung cancer, based on information from the China Drug Clinical Trial Registration and Information Publicity Platform. It is important to note that this information is dynamically updated, so please refer to the information obtained from your consultation with your doctor.
To participate in a clinical trial for PD-1/PD-L1 inhibitor therapy, you will need to talk to your primary care physician who will determine if you are eligible for enrollment and help you apply.
| Type | Drugs |
Company |
Registration test number |
Trial status |
Indications |
Trial phase |
|
PD-1 inhibitors |
Nivolumab |
BMS |
CTR20170731 |
In progress, not yet recruited |
Treated advanced or recurrent solid tumors |
Stage III |
|
CTR20170694 |
On-going, recruiting |
Extensive stage small cell lung cancer |
Stage III |
|||
|
CTR20170541 |
On-going, recruiting |
Advanced or metastatic NSCLC (EGFR mutation-positive, T790M mutation-negative, failed first-line TKI therapy) |
Phase III |
|||
|
CTR20170340 |
On-going, recruiting |
NSCLC |
Stage III |
|||
|
CTR20160578 |
In progress, recruitment complete |
Limited or extensive stage small cell lung cancer |
Stage III |
|||
|
CTR20150767 |
In progress, recruitment complete |
Advanced or metastatic NSCLC |
Stage III |
|||
|
CTR20171020 |
On-going, recruiting |
NSCLC |
Other |
|||
|
CTR20150755 |
In progress, not yet recruited |
Advanced or recurrent solid tumors |
Other |
|||
|
Pembrolizumab |
Merzadone |
CTR20170044 |
On-going, recruiting |
Metastatic squamous NSCLC |
Stage III |
|
|
CTR20160205 |
On-going, recruiting |
NSCLC with disease progression after platinum-containing therapy and positive PD-L1 expression |
Other | |||
|
CTR20160097 |
In progress, recruitment complete |
Advanced or metastatic NSCLC with positive PD-L1 expression and primary treatment |
Other | |||
|
SHR-1210 |
Henry |
CTR20170322 |
On-going, recruiting |
Advanced NSCLC |
Stage III |
|
|
CTR20170299 |
On-going, recruiting |
Advanced NSCLC |
Stage II |
|||
|
CTR20170090 |
On-going, recruiting |
Combining Apatinib for Advanced NSCLC |
Stage II | |||
|
CTR20160248 |
On-going, recruiting |
Solid tumors |
Stage I |
|||
|
CTR20160175 |
On-going, recruiting |
Advanced solid tumors |
Stage I |
|||
|
IBI308 |
SINDA |
CTR20160735 |
On-going, recruiting |
Solid tumors |
Stage I |
|
|
CTR20170380 |
On-going, recruiting |
Advanced or metastatic squamous NSCLC |
Other |
|||
|
BGB-A317 |
Baekje Shenzhou |
CTR20171112 |
On-going, recruiting |
NSCLC |
Other |
|
|
CTR20170361 |
On-going, recruiting |
Lung cancer |
Other |
|||
|
CTR20160871 |
On-going, recruiting |
Solid tumors |
Stage I-II |
|||
|
JS001 |
Juniper |
CTR20180275 |
On-going, recruiting |
Advanced NSCLC |
Other |
|
|
CTR20160274 |
On-going, recruiting |
Advanced or recurrent malignancy |
Stage I |
|||
|
PD-L1 inhibitors |
Atezolizumab |
Roche |
CTR20171629 |
In progress, not yet recruited |
Primarily treated advanced or recurrent or metastatic NSCLC |
Other |
|
CTR20170064 |
On-going, recruiting |
Stage IV non-squamous NSCLC not previously treated with chemotherapy |
Stage III |
|||
|
CTR20160988 |
On-going, recruiting |
Extensive stage small cell lung cancer stage III |
Other |
|||
|
Durvalumab |
AstraZeneca |
CTR20170012 |
On-going, recruiting |
Advanced NSCLC |
Stage III |
|
|
TQB2450 |
Zhengda Tianqing |
CTR20180272 |
In progress, not yet recruited |
Advanced malignancy |
Stage I |
|
|
KN035 |
Thoughtfulness/Corning Jerry |
CTR20170036 |
On-going, recruiting |
Advanced solid tumors |
Stage I |
(Note: BMS, Bristol-Myers Squibb; TKI, tyrosine kinase inhibitor)
The main hospitals and trial leaders undertaking these trials include: Yilong Wu, Guangdong Provincial People’s Hospital; Tension, Center for Cancer Control, Sun Yat-sen University; Ying Cheng, Jilin Provincial Cancer Hospital; Yuankai Shi, Cancer Hospital, Chinese Academy of Medical Sciences; Cai-cun Zhou, Shanghai Pulmonary Hospital; and Shun Lu, Shanghai Chest Hospital.
Note: Drug Clinical Trial Registration and Information Disclosure Platform; http://www.chinadrugtrials.org.cn/eap/main
Related reading:
Co-reviewed by: Guangdong Provincial People’s Hospital Guangdong Provincial Lung Cancer Institute Dr. Wang Zhen, Associate Chief Physician Dr. Linlin Lai, Dr. Siyang Liu