2022 AWE Professor Zhou Qing interpretation and Professor Wu Yilong commented on the GEMSTONE-301 study

Clinical research and development ideas and results

Suglilimab is a fully human, full-length IgG4 targeted PD-L1 monoclonal antibody, unlike other PD-L1 monoclonal antibodies, suglilimab retains antibody-dependent cell-mediated phagocytosis (ADCP) and has a dual anti-tumor mechanism: it can simultaneously induce T cells and macrophages to kill tumor cells
.
First, by blocking the PD-1/PD-L1 signaling pathway, the anti-tumor effect
of T cells is enhanced.
Second, the antibody Fc segment binds to the macrophage surface FcγR to activate the ADCP effect
.

The GEMSTONE-301 study was tailored for Chinese patients

GEMSTONE-301 is designed to explore the efficacy
of suglilimab for consolidation therapy in progression-free phase III patients following chemoradiotherapy.
At the same time, the efficacy of immunoconsolidation therapy after receiving cCRT or sCRT was explored, and stage III unresectable Chinese patients were included, and drivers positive patients
were excluded.
Professor Zhou Qing pointed out that the study appropriately relaxed the inclusion criteria for patients with minor injuries to liver and kidney function, and also included patients with grade 1 radiation pneumonia in the study, which is closer to the real clinical situation
.

Latest results

Baseline characteristics showed that the population enrolled in the GEMSTONE-301 study was more "refractory", with more stage IIIB/IIIC and more
squamous cell carcinoma.

Figure baseline characteristics

On this basis, the study still achieved good results and reached the primary endpoint
.
As of 1 March 2022, the median follow-up was 27.
1 months and 23.
5 months in the Sougley and comfort groups, respectively, and the median PFS assessed by BICR was 10.
5 months and 6.
2 months, respectively (HR=0.
65).

Suglilimab significantly reduces the risk of disease progression by 35%
in the general population.
The median PFS in the sCRT subgroup was 8.
1 versus 4.
1 months (HR=0.
57), and the median PFS in the cCRT subgroup was 15.
7 vs 8.
3 months (HR=0.
71),
respectively.
Professor Zhou Qing pointed out that the results of the concurrent chemoradiotherapy group were similar to the PACIFIC study, and the results of the general population were greatly
affected by the population in the "sequential chemoradiotherapy" group.

Figure research results

The duration of response was 24.
1 months and 6.
9 months
in the suglilimab and placebo groups, respectively.
There is no doubt that patients who can benefit from immunotherapy will have long-lasting
results.

Professor Zhou Qing pointed out that as of now, the only immature data is OS results, and further OS analysis results
are expected to be released next year.
In terms of safety, the incidence of adverse events in both groups was similar, which shows that immunotherapy will produce related adverse events, such as changes in thyroid function
.
For pneumonia, which is of greater concern to clinicians, the incidence was similar
in both groups.

Based on this, suglilimab, as a consolidation therapy after concurrent or sequential chemoradiotherapy, has been included in the guidelines and expert consensus, including the 2022 version of the guidelines for the diagnosis and treatment of non-small cell lung cancer (CSCO) (level III recommendation), the clinical application guidelines for immune checkpoint inhibitors (CSCO) 2022 (class IA evidence), and the expert consensus on the diagnosis and treatment of stage III non-small cell lung cancer 2022 (degree of evidence: medium; Recommended intensity: medium).

Reviews of big coffee - Professor Wu Yilong: One of the most important clinical studies in five years

Prof.
Yilong Wu

Guangdong Provincial People's Hospital

The GEMSTONE-301 study is a clinical trial
to explore the efficacy of immune consolidation therapy in patients with stage III NSCLC who achieve stable (SD) or partial remission (PR) after concurrent or sequential chemoradiotherapy.
Professor Wu Yilong believes that the GEMSTONE-301 study is one of the most important clinical studies in the field of phase III unresectable NSCLC in the past five years, because the study takes into account a high proportion (40%-50%) of patients who have been previously ignored by PACIFIC studies
.
Data from the United States, the United Kingdom and China all show that 40%-60% of patients do not receive concurrent chemoradiotherapy, so this proportion of patients should not be ignored, which is the significance of the GEMSTONE-301 study and why it is called one of
the most important clinical studies in five years.

For the GEMSTONE-301 study, we should focus on two points: first, whether the results of PACIFIC are relatively consistent
with the concurrent chemoradiotherapy group.
After a long enough follow-up, results published at the WCLC this year showed that the median PFS of patients in the concurrent chemoradiotherapy group reached 15.
7 months, which is very close to
the PACIFIC study data.
THEREFORE, THE GEMSTONE-301 DATA FURTHER CONFIRM PACIFIC'S FINDINGS
.
This suggests the superiority of immunoconsolidation therapy followed by concurrent chemoradiotherapy
.

Second, whether patients receiving sequential chemoradiation can also benefit from immunotherapy
.
GEMSTONE-301 clearly suggests that the benefit of consolidation immunotherapy after sequential chemoradiotherapy even exceeds that of concurrent chemoradiotherapy, with an HR value of 0.
57, reducing the risk of disease recurrence by nearly 50%, which is the second huge contribution
.
Confirmed by GEMSTONE-301, in clinical practice, for unresectable patients, whether after simultaneous or sequential chemoradiotherapy, suglilimab can be used as a consolidation therapy, which has been approved by CDE in China, has also been written into various guidelines, and is also the first study
in the world to remind us that suglilimab can be used as a conventional treatment after sequential chemoradiotherapy.

However, it should be emphasized that: First, sequential chemoradiotherapy cannot be given to all patients because the HR of sequential chemoradiotherapy is better than concurrent chemoradiotherapy, which is a misunderstanding
.
Overall, patients with concurrent chemoradiotherapy lived longer, surviving better than sequential chemoradiotherapy
in both the experimental and placebo groups.
Therefore, concurrent chemoradiotherapy should be preferred in stage III unresectable patients, but sequential chemoradiotherapy may be used in patients who cannot receive concurrent chemoradiotherapy
.

Second, GEMSTONE-301 was selected for advanced stages, with only 25.
4% of stage IIIA patients, compared with about 60% of PACIFIC stage IIIA patients
.
After including patients with advanced disease, GEMSTONE-301 also demonstrated the reliability
of this model.

Third, in terms of safety, the safety of sequential chemoradiotherapy is better than that of concurrent chemoradiotherapy, based on this, in clinical practice, for patients with better physical condition and relatively young, sequential suglilimab or duvalumab should be treated with concurrent chemoradiotherapy as much as possible, but for patients with poor physical condition, or older age, or other reasons need to receive sequential chemoradiotherapy, we can only choose suglilimab as maintenance therapy
.