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- Elisrasib monotherapy achieved a 78.0% objective response rate (ORR) and a median progression-free survival (PFS) of 12.4 months (n=41) in first-line treatment of KRAS G12C-mutated advanced NSCLC, with consistent efficacy across all PD-L1 expression subgroups.
- Elisrasib combined with pembrolizumab achieved an 81.3% ORR (n=48) in first-line treatment, with a 12-month PFS rate of 53.7%.
ShanghaiJune 1, 2026 /PRNewswire/ — D3 Bio, a global clinical-stage biotechnology company dedicated to developing innovative cancer therapies, today announced first-line treatment data from an ongoing Phase I/II clinical study evaluating its next-generation KRAS G12C inhibitor, elisrasib (D3S-001). The study assessed the efficacy and safety of elisrasib as monotherapy and in combination with pembrolizumab in patients with KRAS G12C-mutated (G12Cmut) non-small cell lung cancer (NSCLC). The data were presented at the Clinical Science Symposium of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Study results showed that both monotherapy and combination regimens of elisrasib demonstrated a favorable safety and tolerability profile in first-line G12C-mutated NSCLC patients, along with encouraging antitumor activity across different PD-L1 expression levels, supporting further development in the first-line setting.
Elisrasib Monotherapy in First-Line KRAS G12C-Mutated NSCLC
Elisrasib monotherapy showed highly promising preliminary antitumor activity. In this cohort, a total of 43 previously untreated G12C-mutated NSCLC patients received elisrasib 600 mg once daily (21-day cycle), with a median follow-up of 8.5 months. Among 41 evaluable patients, the ORR was 78.0%, with efficacy observed across all PD-L1 expression subgroups: ORR was 76.2% (n=21) in patients with PD-L1 TPS <1%, and 80.0% (n=20) in those with TPS ≥1%. The disease control rate (DCR) was 95.1%.
Median PFS was 12.4 months (95% CI: 6.8, not reached), with a 12-month PFS rate of 50.8%. Median overall survival (OS) was not reached, with a 12-month OS rate of 90.0%. As of the data cutoff date, 60.5% of patients remained on treatment.
In terms of safety, elisrasib monotherapy was generally well tolerated, with a ≥Grade 3 treatment-related adverse event (TRAE) rate of 7.0% and a serious TRAE rate of 2.3%. No TRAE-related discontinuations or dose reductions occurred.
Elisrasib Combined with Pembrolizumab in First-Line KRAS G12C-Mutated NSCLC
In the combination cohort, a total of 52 previously untreated G12C-mutated NSCLC patients received elisrasib 600 mg once daily combined with pembrolizumab 200 mg every 3 weeks (Q3W), with a median follow-up of 5.7 months. Notably, the elisrasib dose in the combination regimen was its RP2D (600 mg QD), enabling complete coverage of the KRAS G12C target.
Elisrasib combined with pembrolizumab demonstrated compelling antitumor activity in previously untreated G12C-mutated NSCLC patients. Among 48 evaluable patients, the ORR was 81.3%, with efficacy observed across all PD-L1 expression subgroups: ORR was 70.6% (n=17) in patients with PD-L1 TPS <1%, 72.7% (n=11) in those with TPS 1%–49%, and 95.0% (n=20) in those with TPS ≥50%. The DCR was 97.9%.
Median PFS was not reached (95% CI: 8.4, not reached), with 6-month and 12-month PFS rates of 74.6% and 53.7%, respectively. Median OS was not reached, with a 12-month OS rate of 88.8%. As of the data cutoff date, 82.7% of patients remained on treatment.
The safety profile of the combination regimen was consistent with the known safety profiles of each agent individually. The ≥Grade 3 TRAE rate was 32.7%, with most serious adverse events related to pembrolizumab; the serious TRAE rate was 17.3%. No new or unexpected safety signals were observed for elisrasib, and the overall safety profile was superior to the current standard of care, pembrolizumab combined with chemotherapy.
Expert Commentary
Professor Shun Lu from Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, and the study presenter, stated: “The first-line data for elisrasib are encouraging. Whether as monotherapy or in combination with pembrolizumab, it demonstrates consistently potent antitumor activity across different PD-L1 expression subgroups. Its favorable tolerability and rapid onset of action fully highlight the clinical application potential of this drug for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC).”
Dr. Zhijian Chen, Founder, Chairman, and CEO of D3 Bio, said: “Elisrasib has shown highly promising efficacy signals in both monotherapy and combination therapy for first-line NSCLC, bringing new hope to this patient population that has long lacked effective treatment options. We believe these results support the continued advancement and accelerated development of elisrasib in Phase III randomized studies.”