JCO: Professor Wang Jie's team found that Torpalimab combined with chemotherapy works well in the treatment of non-small cell lung cancer

In recent years, immunotherapy has developed rapidly, bringing new hope
to patients with advanced lung cancer.
Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers
.
NSCLC is one of the leading causes of cancer-related death and the highest incidence of all cancers worldwide
.
There are large-scale clinical trials supporting anti-PD-1/PD-L1 combination chemotherapy as standard first-line therapy
for advanced NSCLC without driver mutations.
However, further exploration is needed for predictive biomarkers that can identify beneficiary patient populations
.

On October 7, 2022, Professor Wang Jie's team at the Chinese Academy of Medical Sciences published a paper entitled "Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter" in the Journal of Clinical Oncology Randomized Phase III Trial (CHOICE-01)"
.
The study investigated the efficacy and safety
of Torpalimab (tolipalimab) combination chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC).

https：//ascopubs.
org/doi/10.
1200/JCO.
22.
00727

1.
Research background

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers
.
NSCLC is one of the leading causes of cancer-related death and the highest incidence of all cancers worldwide
.
China accounts for about one-third
of new cases and cancer deaths worldwide.
In patients with advanced NSCLC without driver mutations, conventional platinum-based chemotherapy has been the standard first-line treatment
, despite unsatisfactory clinical benefits.

Immune checkpoint inhibitors, represented by programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) antibodies, have significantly changed the treatment status
of advanced NSCLC because their efficacy is better than traditional chemotherapy.
There are large-scale clinical trials supporting anti-PD-1/PD-L1 combination chemotherapy as standard first-line therapy
for advanced NSCLC without driver mutations.
However, further exploration is needed for predictive biomarkers that can identify beneficiary patient populations
.
Therefore, comprehensive endpoint analysis and biomarker exploration
are warranted in rigorously designed large-scale clinical trials of first-line chemotherapy immunotherapy for NSCLC.

Torpalimab is a humanized IgG4K monoclonal antibody specific to human PD-1
.
Through crystal structure analysis, it was found that it has a different domain
on PD-1 than nivolumab and pembrolizumab.
In a preclinical study, torpalimab promoted antigen-specific interferon-γ production more than nivolumab
.
Early clinical trials of Toripalimab have also shown promising antitumor activity
in advanced NSCLC.

2.
Research overview

In the CHOICE-01 study, the researchers compared toripalimab plus chemotherapy with placebo plus chemotherapy as first-line treatment for patients with advanced NSCLC without EGFR/ALK-driven mutations
.

CHOICE-01 is a multicenter, randomized, double-blind, placebo-controlled phase III study conducted
at 59 medical centers in China.
Eligible patients must be untreated, locally advanced (stage IIIB or IIIC), or metastatic NSCLC, or non-squamous NSCLC who have completed neoadjuvant/adjuvant therapy at least 6 months prior to enrollment and have excluded EGFR or ALK-driven mutations
.

Patients were randomly assigned 2:1 to receive either toripalimab or placebo plus chemotherapy
.
Patients are given a 240 mg intravenous dose of toripalimab or placebo every 3 weeks and maintain a basic care regimen
.
Tumor evaluation is performed at baseline, every 6 weeks for the first 12 months, and every 9 weeks thereafter
.

Results of progression-free survival (PFS) and overall survival (OS) analyses showed a statistically significant and clinically significant improvement
in the addition of toripalimab to standard first-line chemotherapy compared with chemotherapy alone, regardless of PD-L1 expression.

The researchers also used whole exome sequencing for genomic analysis
of tumor biopsies and paired PBMCs.
Further analysis revealed gene mutations that significantly interacted with therapeutic effects, including RB1, KEAP1 and SMARCA4
.
Patients with SMARCA4 mutations, especially in the non-squamous subgroup (n = 33), had PFS in the toripalimab group significantly better than those in the
placebo group.
In contrast, patients with RB1 mutations (n = 21) in the squamous subgroup had worse PFS than the toripalimab group than the placebo group, suggesting that they may not benefit from
combination therapy.

3.
Research summary

In conclusion, the study revealed that PFS and OS added to chemotherapy in untreated patients with advanced NSCLC are superior to chemotherapy alone and have a manageable safety profile
.
These results support the use of toripalimab in combination with chemotherapy as first-line treatment
for patients with advanced NSCLC without EGFR/ALK mutations.

Resources:

https://ascopubs.
org/doi/10.
1200/JCO.
22.
00727