Abstract LBA79
Background
GEMSTONE-303 is a randomized, double-blinded, multi-center phase 3 trial evaluating sugemalimab (suge), a full-length, fully human anti-PD-L1 mAb + CAPOX vs placebo + CAPOX as the first-line treatment for patients (pts) with advanced G/GEJ adenocarcinoma. It is the first reported phase 3 trial of an anti-PD-L1 mAb in this disease that met the dual primary endpoints of PFS and OS. Here, we report the final analysis results of dual primary endpoints.
Methods
Eligible pts with previously untreated, no known HER2-positive status, PD-L1 expression ≥5%, unresectable advanced or metastatic G/GEJ adenocarcinoma were randomized 1:1 to receive suge/placebo (1200 mg, Q3W, IV) + CAPOX (capecitabine, 1000 mg/m2, PO, BID, D1-14, Q3W; oxaliplatin, 130 mg/m2, IV, Q3W; max 6 cycles). Stratification factors were ECOG PS (0 or 1) and PD-L1 expression levels (5-9% or ≥10%). Primary endpoints were PFS and OS. Data cutoff dates of the preplanned PFS and OS final analyses were 6 Aug 2022 and 9 Jul 2023, respectively.
Results
A total of 479 pts were randomized to suge+CAPOX (N=241) and placebo+CAPOX (N=238) arms between 9 Apr 2019 and 29 Dec 2021. The PFS and OS final analysis showed a significant improvement of the dual primary endpoints with suge+CAPOX vs placebo+CAPOX. The ORR was 68.6% with suge+CAPOX and 52.7% with placebo+CAPOX. The OS benefits were observed across all subgroups. The incidences of G3-5 suge/placebo-related AEs were 31.1% in suge+CAPOX arm and 28.7% in placebo+CAPOX arm. No new safety signals were observed. Table: LBA79
| PD-L1 Expression Level >=5% | Suge+CAPOX | Placebo+CAPOX |
| N=241 | N=238 | |
| PFS (Months) | ||
| Median (95% CI) | 7.62 (6.37, 7.89) | 6.08 (5.06, 6.44) |
| P-value | <0.0001 | |
| HR (95% CI) | 0.66 (0.54, 0.81) | |
| OS (Months) | ||
| Median (95% CI) | 15.64 (13.27, 17.81) | 12.65 (10.64, 14.06) |
| P-value | 0.0060 | |
| HR (95% CI) | 0.75 (0.61, 0.92) | |
| OS Rate | ||
| 12 Months (95% CI) | 61.25% (54.77%, 67.08%) | 52.02% (45.44%, 58.18%) |
| 24 Months (95% CI) | 29.90% (23.79%, 36.23%) | 23.28% (17.81%, 29.18%) |
| PD-L1 Expression Level >=10% | N=130 | N=128 |
| PFS (Months) | ||
| Median (95% CI) | 7.79 (6.77, 9.99) | 5.52 (4.83, 6.67) |
| P-value | 0.0001 | |
| HR (95% CI) | 0.58 (0.43, 0.77) | |
| OS (Months) | ||
| Median (95% CI) | 17.81 (14.36, 21.16) | 12.45 (9.89, 13.86) |
| P-value | 0.0022 | |
| HR (95% CI) | 0.64 (0.48, 0.85) |
Conclusions
Sugemalimab in combination with CAPOX demonstrates statistically significant and clinically meaningful improvements in PFS and OS, with a manageable safety profile. These findings support suge+CAPOX as new first-line treatment option for pts with PD-L1 expression ≥5%, advanced G/GEJ adenocarcinoma.
Clinical trial identification
NCT03802591.
Editorial acknowledgement
Medical writing and editorial assistance were provided by Mengxin Chen from CStone Pharmaceuticals, funded by the study sponsor.
Legal entity responsible for the study
CStone Pharmaceuticals.
Funding
CStone pharmaceuticals.
Disclosure
J. Luo: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (Su Zhou) Co., Ltd.. D. Zhu: Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.. H. Wang: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.. Y. Xu: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.. Q. Shi: Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.. J.J. Yang: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares, CStone Pharmaceuticals (Su Zhou) Co., Ltd.: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Member of Board of Directors: CStone Pharmaceuticals (Su Zhou) Co., Ltd.. L. Shen: Financial Interests, Personal, Other, Consulting fees: Mingji biopharmaceutical, Haichuang pharmaceutical, Herbour biomed; Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, BI, Sanofi, Roche, SERVIER, AZ; Financial Interests, Institutional, Funding: Beijing Xiantong Biomedical Technology, Qilu Pharmaceutical, ZaiLab Pharmaceutical (Shanghai), Alphamab Oncology, Yaojie Ankang (Nanjing) Technology Co., Ltd., BeiGene, Ltd., Qiyu Biotechnology (Shanghai) Co., Ltd., BriSTAR immunotech; Financial Interests, Institutional, Local PI: Merck Healthcare KGaA, Roche; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceutical, Innovent, BeiGene, Ltd., Qilu Pharmaceutical, NovaRock Biotherapeutics Limited. All other authors have declared no conflicts of interest.
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