After O+Y, the double-free treatment T+D attacked liver cancer again, and the OS exceeded 18 months!

Liver cancer is a common clinical malignant tumor of the digestive system.
Especially in China, it is characterized by high incidence and refractory treatment.

Liver cancer is a serious threat to people's health.

Because there are abundant immune cells in the liver, including sinusoidal endothelial cells, macrophages (Kupffer cells), etc.
, liver cancer has the conditions, basis and basis for receiving immunotherapy.

Author: cornflower This article is the author's permission NMT Medical publish, please do not reprint without authorization.

Since 2015, the results of liver cancer immunotherapy research have been announced one after another, continuously attacking the deadlock in the treatment of liver cancer.
Among them, CheckMate-040 research, as the pioneer, plays a role in promoting the development of immunotherapy in the field of liver cancer.
A pivotal role.

Coincidentally, at the just-concluded 2021 HCC-TAG Conference, Tremelimumab (CTLA-4 monoclonal antibody) combined with Durvaluamb (duvalizumab, PD-L1 monoclonal antibody) (T+D) The results of a phase II clinical study (Study 22 study, NCT02519348) for the treatment of immune checkpoint inhibitors for unresectable hepatocellular carcinoma (uHCC) were also announced, once again igniting hope for a breakthrough in the treatment of liver cancer.

Let's take a look at these two double-free studies together.

CheckMate-040 study [1] On March 11, 2020, the U.
S.
Food and Drug Administration (FDA) officially approved Nivolumab (Nivolumab, "O drug") in combination with Ipilimumab (Ipilimumab, abbreviated as " Drug Y") is used for hepatocellular carcinoma (HCC) patients who have previously received sorafenib treatment.On October 1, 2020, JAMA magazine published the complete data of the CheckMate 040 randomized clinical trial.
The study evaluated the efficacy and safety of O+Y in the treatment of advanced HCC patients who were previously treated with sorafenib.
A new and efficient treatment mode.

CheckMate 040 is a multi-center, open-label, multi-cohort, phase I/II study.

The enrolled patients were Sorafenib-treated advanced HCC patients.
A total of 148 patients were randomly divided into groups: Group A (n=50): O drug 1mg/kg combined with Y drug 3mg/kg, once every 3 weeks, sequential O drug 240mg, once every 2 weeks; B group (n=49): O drug 3mg/kg combined with Y drug 1mg/kg, once every 3 weeks, sequential O drug 240mg, once every 2 weeks; C group (n= 49): O drug 3mg/kg (once every 2 weeks) combined with Y drug 1mg/kg (once every 6 weeks).

Study results: Group A vs.
Group B vs.
Group C: Investigator-assessed objective response rate (ORR): 32% vs 27% vs 29%; median duration of response (mDOR): not assessable (NE) vs 15.
2 months vs 21.
7 months.

The Independent Center for Blinding (BICR) assessed ORR according to RECIST (Efficacy Evaluation Criteria for Solid Tumors) v 1.
1: 32% vs 31% vs 31%; complete response (CR): 8% vs 6% vs 0%; disease control rate (DCR) ): 54% vs 43% vs 49%; mDOR: 17.
5 months vs 22.
2 months vs 16.
6 months; BICR according to RECIST assessment ORR: 34% vs 33% vs 31%.

Subgroup analysis showed that patients with hepatitis B and PD-L1 negative patients can still benefit from dual immunotherapy.

The success of the CheckMate 040 study not only brings a higher-efficiency second-line treatment plan for patients with advanced liver cancer, but also brings a different kind of treatment thinking.

Study 22 study [2] Study 22 is an international multi-center, open-label, randomized controlled phase II registered clinical trial, which aims to evaluate different doses of tremelimumab (T) + duvalizumab (D), T single The safety and effectiveness of single-drug and D drugs for first-line/second-line treatment of patients with advanced uHCC.

332 patients with advanced uHCC who had progressed on sorafenib treatment or were intolerant/refusal of sorafenib treatment, and had not received immune checkpoint inhibitor therapy in the past, were randomly divided into 4 groups: T300+D group (n=75 Example): T drug 300 mg + D drug 1500 mg, followed by D drug 1500 mg after a course of treatment, Q4W (once every 4 weeks); single drug D group (n=104 cases): D drug 1500 mg single use, Q4W; single drug T group (n=69 cases): T drug 750 mg alone, Q4w for the first 7 courses, Q12W after 7 courses; T75+D group (n=84 cases): T drug 75 mg + D drug 1500 mg, followed by D drug 1500 mg, Q4W after 4 consecutive courses.

Research results: Clinical benefits were observed in all patients in the treatment groups.
Among them, the T300+D group had the most obvious advantage.
After only one course of T drug 300 mg + D drug 1500 mg regimen, the sequential D drug 1500 mg was obtained.
The median OS [95%CI: 10.
78-27.
27] and 24% ORR (RECIST v1.
1) were up to 18.
73 months.

The mDOR of the T300+D group has not been reached, and the mDOR of the other three groups has exceeded 11 months.

In this study, the median OS of the T300+D group reached 18.
73 months, and the DOR of the other three groups reached 11 months.
Compared with the natural median OS of patients with advanced HCC in China, which is only 3 to 4 months, it is quite commendable.
Efficacy data.

In addition to double immune therapy, in the field of advanced liver cancer treatment, there are many immune combination programs that are constantly updating the results, summarized as follows: (Data from References 3, 4, 5) Conclusion Compared with standard chemotherapy, immuno-oncology drugs are clinically effective.
The research shows greater advantages, such as longer duration of efficacy and survival time, which is highly anticipated. But returning to the current clinical practice of liver cancer in China, the results of clinical trials need to pass more tests before they can be used to guide clinical practice.

In the current clinical practice, the choice of treatment plan should consider evidence-based evidence and real-world data (whether it is more suitable for the clinical practice of Chinese patients).

Although the progress of liver cancer immunotherapy is not as fast as lung cancer, melanoma and other tumors, liver cancer is a refractory tumor, and every little progress is enough to bring us great joy and motivation! In the future, "combined boxing" therapy, i.
e.
combination therapy of immuno-oncology drugs, will still be the focus and hot spot of clinical research. References: 1.
Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib The CheckMate 040 Randomized Clinical Trial; 2.
Kelley KR, Masatoshi K, Harris W, etal.
Study 22: a randomized, phase 2 trial of durvalumab and tremelimumab inadvanced HCC.
Presented at: 2021 Annual HCC-TAG Conference; March 25-27, 2021; Virtual.
Accessed March 26, 2021; 3.
Patient-reported outcomes (PROs) from the Phase III IMbrave150 trial of atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC); 4.
Retrieved Jan 13, 2021, from http://innoventbio.
com /#/news/247;5.
Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma.