Second-line indications for liver cancer: What is the efficacy of domestic PD-1 when drug O is withdrawn and drug K is approved?

Author: Xiao Guang

On July 23, Bristol-Myers Squibb (BMS) announced that after consultation with the FDA, it would voluntarily withdraw Opdivo (nivolumab, commonly known as O drug) in the U.

BMS's decision is based on the meeting of the Oncology Drug Advisory Committee in April this year and subsequent discussions with the FDA

Drug O encounters Waterloo, drug K gets accelerated approval

Drug O was first approved for the second-line treatment of HCC under the FDA's accelerated approval plan in September 2017, and is the first immunotherapy drug approved for HCC

The accelerated approval is based on data from the Phase I/II CheckMate-040 trial

However, in the confirmatory clinical trial CheckMate-459, according to the pre-specified analysis, O drug and sorafenib first-line treatment of liver cancer, although the ORR data consistent with the previous accelerated approval was achieved, the primary endpoint of OS did not reach the statistics.

CheckMate 459 Primary Endpoint OS Achieved Negative Results (Source: 2019 ESMO)

CheckMate 459's PFS has a negative result (Source: 2019 ESMO)

It is worth noting that the second-line liver cancer PD-1-Merck’s Keytruda (pembrolizumab, pembrolizumab, commonly known as K drug) compared with placebo for the second-line treatment of advanced HCC Phase III study KEYNOTE-240 results released: This study did not achieve the established statistically significant OS and progression-free survival (PFS) benefits

The median OS of the K drug group and the placebo group were 13.

The OS results of KEYNOTE-240 did not meet statistical assumptions (Source: Reference 2)

Domestic PD-1 helps immunotherapy for liver cancer

Drug O is the world's first and China's first PD-1 inhibitor approved for marketing

Part of the reason for the failure of Drug O may be the principle of immune checkpoint inhibitors: it takes time to adjust and mobilize the immune balance in the body, and the body functions of patients with advanced liver cancer enter the downward channel, which makes many patients unable to maintain the normal immune system in the body.

After the O drug second-line liver cancer indication is withdrawn, the K drug can continue to be used for the treatment of second-line hepatocellular carcinoma in the United States, but it has not yet been approved in China

Carrelizumab

In 2020, the humanized PD-1 monoclonal antibody developed by Hengrui Medicine-Carrelizumab (trade name: Erica) was approved by NMPA for the second-line treatment of HCC, becoming the first approved treatment in China PD-1 inhibitor for liver cancer

This approval is mainly based on the results of a national multi-center phase II clinical study of carrelizumab in the treatment of advanced hepatocellular carcinoma in China that has failed previous systemic treatments

Since the advent of carrelizumab, it has been widely recognized in the oncology field at home and abroad

Tilelizumab

In June of this year, NMPA formally approved the second domestic PD-1 tislelizumab (trade name: Beizean) as a single drug for HCC patients who have undergone at least one systemic treatment

This is a single-arm, multi-center, open-ended, phase II study conducted globally

Liver cancer is one of the most "Chinese characteristics" malignant tumors

PD-1/PD-L1 immunosuppressants have been the hottest topic in the anti-cancer field in recent years
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Such drugs benefit a wide range of super survivors and may bring clinical cures, and have attracted the attention of cancer patients
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Among domestic drugs, carrelizumab and tislelizumab are at the forefront of domestic liver cancer immune drugs, and the future is promising
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We also look forward to more therapeutic drugs/programs coming out in the future to benefit more liver cancer patients
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Reference

1.
Bruno Sangro, Chiun Hsu, Yoon-Koo Kang, et al.
CheckMate 040: Efficacy, Hepatic Safety, and Biomarkers of Nivolumab + Ipilimumab Combination Therapy in Patients with Advanced Hepatocellular Carcinoma.
AASLD 2019 Abstract: 0200.

2.
Pembrolizumab (pembro) vs placebo (pbo) in patients (pts) with advanced hepatocellular carcinoma (aHCC) previously treated with sorafenib: Updated data from the randomized, phase III KEYNOTE-240 study.
2021ASCO GI, abs268.

3.
Qin S, Ren Z, Meng Z, et al.
Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, randomised, open-label, parallel-group, phase 2 trial.
Lancet Oncol.
Feb 26,2020.

4.
Results from a global Phase 2 study of tislelizumab, an investigational PD-1 antibody, in patients with unresectable hepatocellular carcinoma.