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Sugemalimab Offers Another Option in Unresectable NSCLC

Vienna, Austria — Updated clinical trial data suggest that the new immunotherapy sugemalimab, which is approved in China, could offer another option for treatment of patients with unresectable stage III non–small cell lung cancer (NSCLC),

Sugemalimab was shown to improve progression-free survival (PFS) when compared with placebo when given after both concurrent and sequential chemoradiotherapy in the GEMSTONE-301 trial.

The data from this trial have already led to approval of sugemalimab for this indication in June 2022 in China, where it is is marketed as Cejemly by CStone/Pfizer.

In addition, data from a preplanned interim analysis of this trial have already published in The Lancet Oncology earlier this year.

Now come updated results from a final PFS analysis of this trial, presented on August 7 at the World Conference on Lung Cancer, held in Vienna, Austria, and also virtually online.

They show that overall, in over 380 randomly assigned patients, sugemalimab improved PFS by 35% compared with placebo. The improvement was 43% in patients who were given sequential chemoradiotherapy (sCRT) and by 29% in those treated with concurrent chemoradiotherapy (cCRT).

Preliminary overall survival data suggest a trend for a 39% survival benefit with sugemalimab, which translated into a 40% improvement in sCRT patients and a 25% benefit in those given cCRT.

Lead author Yi-Long Wu, MD, PhD, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China, said that the “take home message” from this study was that sugemalimab “could safely and effectively be used after cCRT or sCRT and become a standard of care in this setting for stage III inoperable NSCLC”.

However, an expert approached for comment was not impressed. Linda W. Martin, MD, MPH, associate professor of surgery, University of Virginia, Charlottesville, Virginia, believes that sugemalimab “is not clearly better than the standard of care” of durvalumab (Imfinzi), which was investigated in PACIFIC 6 in the same treatment paradigm.

Both sugemalimab and durvalimab are monoclonal antibody products directed against programmed cell death ligand 1 (PD-L1),

“My editorial view on this is that, instead of spending money and investing in another drug to develop in the [same] space, why don’t we focus…on access to care and disparities instead of drug development in this area?” Martin commented to Medscape Medical News.

She also had questions about the design of the trial and wondered why patients with an ECOG performance status of 0 received sCRT in this trial.

In his presentation, Wu told the audience that for patients with unresectable stage III NSCLC, the standard of care is cCRT followed by immunotherapy. However, he said that “a substantial proportion of patients cannot tolerate or access cCRT,” and so sCRT is commonly used instead.

Martin also wondered why these patients could not access concurrent chemoradiotherapy. She noted that “about a third of them had sequential chemoradiotherapy but NCCN guidelines say that this should only be used for frail patients.”

She added that the results suggest that sCRT was associated with inferior outcomes compared with cCRT when taking both the active and placebo treatment groups together, and so the question becomes: Why don’t we get more patients to concurrent CRT when they have a good performance status?

Details of the Results

Wu noted that GEMSTONE-301 is the first phase 3 trial in this setting to include both forms of delivery for chemotherapy, concurrent and sequential.

Patients recruited to the trial had not progressed after cCRT or sCRT, had an ECOG performance status of 0 or 1, and had no known sensitizing EGFR, ALK, or ROS1 mutations.

They were randomly assigned to receive intravenous sugemalimab or placebo every 3 weeks for up to 24 months, with PFS assessed by blinded independent central review.

Of 381 patients included in the study, 255 were assigned to sugemalimab and 126 to placebo. The median age of the participants was 60-61 years, and around 92% of participants were men. The majority of patients were in disease stage IIIB, and just over two thirds of the tumors had squamous histology.

After a median follow-up of 27.1 months in the sugemalimab arm and 23.5 months in the placebo arm, the median PFS was 10.5 months and 6.2 months, respectively, at a hazard ratio (HR) for progression of 0.65 (P = .0012).

At 24 months, 38.6% of patients in the active treatment arm had not progressed compared with 23.1% of those assigned to placebo.

Looking at CRT delivery, Wu showed that the HR for progression with sugemalimab vs placebo after sCRT was 0.57 (95% CI, 0.38-0.87), whereas after cCRT, it was 0.71 (95% CI, 0.50-1.00).

However, it was notable that in both the active and placebo treatment arms, the median PFS in the cCRT group was approximately double than that seen with sCRT.

Subgroup analysis suggested that sugemalimab was superior to placebo in patients aged 65 years or younger; those with an ECOG performance status of 0, stage IIIB disease, and a squamous histology; and in patients who waited more than 14 days between their last radiation dose and random assignment into the study.

Although emphasizing that they are immature, Wu also presented results for overall survival, which showed that the HR for death with sugemalimab vs placebo was 0.69 (95% CI, 0.49-0.97). The median overall survival was not reached in patients given sugemalimab compared with 25.9 months reached in the placebo group.

After 24 months, 67.6% of patients in the sugemalimab arm and 55.0% of those assigned to placebo were still alive.

Stratifying the patients by CRT delivery revealed that the HR for overall survival in those treated with sCRT was 0.60 (95% CI, 0.34-1.05), whereas for those given cCRT, it was 0.75 (95% CI, 0.48-1.15).

The overall response rate was 24.5% with sugemalimab and 25.2% with placebo. However, the median duration of response was markedly longer with sugemalimab, at 24.1 months vs 6.9 months.

Wu said there were “no new safety signals”, with 31.0% of sugemalimab patients and 28.6% of those given placebo experiencing a grade 3 or higher treatment-emergent adverse event, and 34.5% and 27.8%, respectively, experiencing a serious treatment-emergent adverse event.

The most common all-grade treatment-related adverse events in the patients who received sugemalimab were hypothyroidism, hyperthyroidism, increased levels of alanine and aspartate aminotransferases, and pneumonitis.

GEMSTONE-301 was funded by CStone Pharmaceuticals and the National Key Research and Development Program of China. The current analysis is supported by EQRx and CStone Pharmaceuticals.

Wu reports relationships with AstraZeneca, Boehringer Ingelheim, Novartis, Takeda, Beigene, Bristol-Meyers Squibb, Eli Lilly, MSD, Pfizer, Roche, Sanofi, and Hengrui.

Martin reports relationships with AstraZeneca, Ethicon, and OnTarget Laboratories.

2022 World Conference on Lung Cancer: Abstract OA02.05. Presented August 7.

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