No tumor cells were found in surgical specimens of nearly 1/4 patients. The world's first IO neoadjuvant phase III study confirmed that nivolumab combined with chemotherapy can significantly improve the pCR of lung cancer patients

*Only for medical professionals to read for reference.
The complete data of CheckMate-816 research has been announced in the form of an oral report at the AACR clinical research plenary meeting in 2021! On April 9-11, 2021, the American Association for Cancer Research (AACR) annual meeting will be held in Washington.

At noon on the 10th, local time, Professor Patrick M Forde from Johns Hopkins Hospital reported that the primary endpoint of the Phase III CheckMate-816 study of immunocombined chemotherapy with neoadjuvant therapy that can cut non-small cell lung cancer (NSCLC) is pathological complete remission ( pCR) complete data.

The CheckMate-816 study was reported at the 2021 AACR virtual conference.
In recent years, neoadjuvant immunotherapy is a hot area of ​​clinical research on early lung cancer.
Clinically, different models including immune monotherapy, immune combined immune and immune combined chemotherapy have been explored.

Immune checkpoint inhibitors (ICIs) can effectively break the immune escape mechanism of tumor cells.
Some studies have shown that ICI neoadjuvant therapy can obtain good feasibility, safety and efficacy for resectable NSCLC, but some key issues are still unknown.
The number, including whether ICI neoadjuvant therapy can ultimately reduce the recurrence of NSCLC after surgery, the selection of benefiting groups and the best treatment plan, etc.

In 2021, the AACR announced the results of the CheckMate-816 study.
This study is the first phase III study in the world to prove that neoadjuvant immunotherapy combined with chemotherapy can bring significant improvement in pCR for patients with resectable NSCLC.
The risk of later recurrence and the improvement of patient survival bring new hope.

The pCR rate of nivolumab + chemotherapy neoadjuvant therapy reaches 24%.
It is not affected by classification, staging, TMB and PD-L1.
Checkmate-816 is a randomized, open-label, multi-center phase III clinical study designed to To evaluate the efficacy and safety of nivolumab combined with chemotherapy for neoadjuvant therapy in patients with resectable NSCLC.

The study included 358 patients who were randomized to receive nivolumab 360 mg combined with platinum-containing dual-drug chemotherapy (once every 3 weeks, up to 3 cycles), or platinum-containing dual-drug chemotherapy (once every 3 weeks, up to 3 cycles).

The primary study endpoints are pCR and event-free survival (EFS) assessed by the blinded independent review committee (BIRC), and secondary endpoints include the primary pathological response (MPR), overall survival (OS), and death or death as assessed by the BIRC.
The time of distant transfer.

Exploratory endpoints include objective response rate (ORR) assessed by BIRC and predictive biomarkers such as PD-L1.

Figure 1.
The results of the CheckMate-816 study design showed that the pCR rate of the group receiving nivolumab combined with chemotherapy before surgery reached 24%, while that of the chemotherapy group alone was only 2.
2% (OR=13.
94, 99%CI: 3.
49- 55.
75, p<0.
0001).

Figure 2.
Subgroup analysis of pCR results shows that regardless of the patient's disease stage, histological type, tumor mutation burden (TMB) and PD-L1 expression level, nivolumab combined with chemotherapy can improve pCR.

Figure 3.
Results of subgroup analysis.
Nivolumab + chemotherapy neoadjuvant therapy also improved MPR and ORR.
In terms of secondary endpoints, the primary pathological remission (MPR) rate of the nivolumab + chemotherapy group was that of the chemotherapy alone group 4 times (36.
9% vs 8.
9%).

Among patients who underwent surgical resection, the MPR rate of the nivolumab + chemotherapy group was significantly higher than that of the chemotherapy alone group (46.
8% vs 12.
7%).

Figure 4.
MPR results The ORR of the nivolumab + chemotherapy group also improved, reaching 54%, compared with 37% in the chemotherapy group alone.

For the patients who were downgraded by imaging evaluation, the ORRs of the nivolumab + chemotherapy group and chemotherapy alone group were 31% and 24%, respectively.

Figure 5.
ORR results The ctDNA clearance rate of nivolumab + chemotherapy group was significantly higher than that of chemotherapy alone group (56% vs 34%).

Analyzing the pCR rate of ctDNA-cleared and uncleared patients in the two groups, it was found that ctDNA clearance was related to pCR.

Figure 6.
MPR results of the CheckMate-816 study.
Nivolumab + chemotherapy neoadjuvant therapy is safe and tolerable.
In terms of safety, the nivoliumab + chemotherapy group and chemotherapy alone group are related to grade 3-4 treatment The incidence of adverse events was 34% and 37%, respectively.

No treatment-related deaths occurred in the nivolumab + chemotherapy group.

Figure 7.
Summary of safety analysis The CheckMate-816 research data released at this conference shows that nivolumab combined with neoadjuvant chemotherapy can bring significant pCR improvement in patients with resectable NSCLC, and in different stages and different tissues Patients with medical type, TMB and PD-L1 expression showed consistent benefits.

Both MPR and ORR improved.

And the combination therapy is well tolerated.

This study provides a new option for neoadjuvant treatment of patients with resectable NSCLC.

Looking forward to the final result of the other primary endpoint EFS.

At the same time, in the future, issues such as neoadjuvant immunotherapy schemes, surgical timing, curative effect evaluation systems, and predictive markers will still need to be explored in clinical practice with a large sample.