Sugemalimab for stage III NSCLC: Efficacy, safety signals sustained in final PFS analysis

In the final progression-free survival (PFS) analysis of the GEMSTONE-301 study, sugemalimab demonstrated sustained efficacy and safety as consolidation treatment for individuals with unresectable stage III non-small cell lung cancer (NSCLC) whose disease had not progressed following either concurrent chemoradiotherapy (cCRT) or sequential CRT (sCRT).

The current results come on the heels of the pre-planned interim PFS analysis showing statistically significant and clinically meaningful PFS improvements with sugemalimab compared with placebo. [Lancet Oncol 2022;23:209-219]

In this phase III trial, 381 participants (median age 60 years, 92 percent male) were randomized 2:1 to receive either sugemalimab 1,200 mg IV Q3W or placebo for up to 24 months. Patients who have tolerated sugemalimab after 24 months and have not had disease progression may continue to receive treatment at the investigators’ discretion. [WCLC 2022, abstract 968]

BICR*-assessed PFS was longer in the sugemalimab vs the placebo arm (median 10.5 vs 6.2 months; stratified hazard ratio [HR], 0.65; p=0.0012). Sugemalimab continued to have the advantage over placebo when participants were stratified by CRT type (median 15.7 vs 8.3 months; stratified HR, 0.71 [cCRT] and 8.1 vs 4.1 months; stratified HR, 0.57 [sCRT]).

PFS rates were higher with sugemalimab vs placebo, both at 24 months (39 percent vs 23 percent) and at 36 months (26 percent vs 0 percent).

Subgroup analysis of PFS consistently favoured sugemalimab over placebo across all subgroups** evaluated.

Overall, median OS was not reached (NR) with sugemalimab and was 25.9 months with placebo (stratified HR, 0.69). A similar trend was seen in the cCRT (median NR vs 32.4 months; stratified HR, 0.75) and sCRT subgroups (median NR vs 24.1 months; stratified HR, 0.60).

OS rates at 24 months were higher with sugemalimab vs placebo in the overall (68 percent vs 55 percent), cCRT (66 percent vs 58 percent), and sCRT cohorts (71 percent vs 54 percent). The same was true for the 36-month OS rates (56 percent vs 30 percent [overall], 54 percent vs 20 percent [cCRT], and 59 percent vs 44 percent [sCRT]).

Objective response rates (complete and partial responses) were similar between the sugemalimab and placebo arms (24.5 percent vs 25.2 percent), but duration of response was longer with the former than the latter (24.1 vs 6.9 months).

Compared with the placebo arm, the incidence of grade ≥3 treatment-related adverse events (AEs) was nearly twice as high with sugemalimab (11 percent vs 6 percent), while the rate of treatment-emergent AEs leading to permanent discontinuation was about threefold higher (16 percent vs 5 percent). Nonetheless, no new safety signals were reported, noted Dr Yi-Long Wu from the Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China, at WCLC 2022.

A potential standard of care?

“[In this final analysis,] sustained PFS benefit and a well-tolerated safety profile were observed [with sugemalimab] … Preliminary OS data showed a trend for benefit favouring sugemalimab,” said Wu.

“cCRT followed by immunotherapy is the standard of care for patients with unresectable stage III NSCLC. However, a substantial proportion of patients cannot tolerate or access cCRT; thus, sCRT is commonly utilized,” Wu noted. “[Our findings suggest that] sugemalimab could be safely and effectively used after cCRT or sCRT and could become a standard of care … for stage III inoperable NSCLC.”

In June 2022, sugemalimab, a full-length, fully human IgG4 monoclonal antibody targeting PD-L1, has gained approval for this indication in China.