elisrasib (D3S-001) / D3 Bio - LARVOL DELTA

Elisrasib (D3S-001), a next-generation GDP-bound KRAS G12C inhibitor, as first-line therapy for KRAS G12C mutation–positive non–small cell lung cancer (NSCLC). (ASCO 2026) - P1/2 | "Both elisrasib monotherapy and in combination with pembrolizumab show strong efficacy and good tolerability as 1L treatments for G12C-mutant NSCLC, warrant for randomized study to evaluate elisrasib as a potential new standard of care. *TRAEs for combo cohort is related to elisrasib and/or pembrolizumab."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

D3S-001, a next generation GDP-bound KRAS G12C inhibitor, as monotherapy in KRAS G12C inhibitor resistant non-small cell lung cancer (AACR 2025) - P1/2 | "In pre-clinical studies, D3S-001 resulted in tumor regression in xenograft models that are resistant to sotorasib (soto) and adagrasib (ada). These findings highlight the potential of D3S-001 to overcome the limitations of earlier KRAS G12Ci and address unmet needs in G12Ci resistant NSCLC, offering a promising therapeutic option for pts with KRAS G12C-mutant cancers."

Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • CDKN2A • EGFR • KRAS • MYC • NTRK1 • NTRK2 • NTRK3 • PIK3CG • TP53

D3S-001, a KRAS G12C inhibitor with rapid target engagement kinetics, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities. (PubMed, Cancer Discov) - P1/2 | "In the presence of growth factors, such as EGF and HGF, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust anti-tumor activity preclinically and translated into promising clinical activity in an ongoing phase 1 trial (NCT05410145)."

Journal • Preclinical • Oncology • KRAS

Safety and efficacy of Elisrasib (D3S-001), a next generation GDP-bound KRAS G12C inhibitor, as monotherapy in advanced non-small cell lung cancer (NSCLC) previously treated with or without a KRAS G12C inhibitor: Results from a phase 1/2 study (AACR 2026) - P1/2 | "Elisrasib monotherapy demonstrates robust and durable efficacy and favorable tolerability in 2L+ NSCLC pts, naïve and refractory to G12Ci."

Clinical • Metastases • Monotherapy • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial. (PubMed, Nat Med) - P1/2 | "The phase 1b expansion phase is ongoing. ClinicalTrials.gov identifier: NCT05410145 ."

Journal • P1 data • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Phase I/II study of D3S-001, a second generation KRAS G12C inhibitor in advanced/metastatic solid tumors with KRAS G12C mutations (ESMO 2024) - P1/2 | "D3S-001, a 2G G12Ci, demonstrated favorable tolerability and consistent promising efficacy across KRAS G12C-mutated NSCLC, CRC, and PDAC."

Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Elisrasib plus Pembrolizumab as First-Line Combination Therapy for Patients with KRAS G12C Mutation–Positive NSCLC (PRNewswire) - "D3 Bio presents first-line data for elisrasib (D3S-001) at ASCO 2026....Fifty-two patients with previously untreated G12Cmut NSCLC received elisrasib 600 mg once daily in combination with pembrolizumab 200 mg every 3 weeks (Q3W), with a median study follow-up of 5.7 months....The combination of elisrasib and pembrolizumab showed highly compelling antitumor activity in patients with previously untreated G12Cmut NSCLC. In 48 efficacy-evaluable patients, an ORR 81.3% was observed across all PD-L1 expression levels, with ORR of 70.6% in patients with PD-L1 TPS <1% (N=17), 72.7% in patients with PD-L1 TPS of 1% to 49% (N=11), and 95.0% in patients with PD-L1 TPS ≥50% (N=20), respectively. The overall DCR was 97.9%. The median PFS was not reached (95% CI: 8.4, NR), with a 6-month PFS rate of 74.6% and a 12-month PFS rate of 53.7%. Median OS was not reached, with a 12-month OS rate of 88.8%."

P1/2 data • Non Small Cell Lung Cancer

A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov) - P1/2 | N=67 | Recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd | Active, not recruiting ➔ Recruiting | Trial completion date: Apr 2028 ➔ Aug 2028 | Trial primary completion date: Apr 2028 ➔ Aug 2028

Enrollment open • First-in-human • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • ROS1

Elisrasib as First-Line Monotherapy for Patients with KRAS G12C Mutation–Positive NSCLC (PRNewswire) - "D3 Bio presents first-line data for elisrasib (D3S-001) at ASCO 2026....Elisrasib monotherapy demonstrated highly promising preliminary antitumor activity. Forty-three patients with previously untreated G12Cmut NSCLC received elisrasib 600 mg once daily in 21-day cycles, with a median study follow-up of 8.5 months. In 41 efficacy-evaluable patients, the overall response rate (ORR) was 78.0% was observed across all levels of PD-L1 expression, with 76.2% ORR in patients with PD-L1 TPS <1% (N=21) and 80.0% in patients with PD-L1 TPS of ≥1% (N=20), respectively. The disease control rate (DCR) was 95.1%. The median progression-free survival (mPFS) was 12.4 months (95% CI: 6.8, NR), 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%."

P1/2 data • Non Small Cell Lung Cancer

D3 Bio Presents KRAS Pipeline Updates at AACR 2026; Elisrasib (D3S-001), a Next-Generation KRAS G12C Inhibitor, Shows Strong Phase 2 Efficacy Across Multiple Tumor Types (PRNewswire) - "In 2L+ KRAS G12Ci-naïve NSCLC (n=68), elisrasib demonstrated robust efficacy at the RP2D (600 mg QD) with an ORR of 58.8%, median duration of response (mDoR) of 16.5 months, and mPFS of 12.2 months. Among late-line NSCLC patients refractory to prior KRAS G12C inhibitor therapy (n=31), an ORR of 32.3%, mDoR of 15.6 months, and mPFS of 8.1 months were recorded. In previously treated CRC, elisrasib showed significant efficacy as both monotherapy (n=32, ORR 46.9%, mDoR 13.1 months, and mPFS 9.5 months) and in combination with cetuximab (n=29, ORR 62.1%, mDoR 7.0 months, and mPFS 8.2 months). Further studies are planned to evaluate optimized combination strategies to enhance the durability of response in CRC. For late-line PDAC, monotherapy (n=20) achieved an ORR of 65.0%, mDoR of 10.8 months, and mPFS of 13.5 months."

P2 data • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

First in human phase 1 study of D3S-002, a purposely designed ERK1/2 inhibitor, in advanced solid tumors with MAPK pathway mutations (AACR 2026) - P1/2 | "D3S-002 demonstrates predictable, dose-proportional PK consistent with its preclinically designed pulsatile exposure profile, supporting its development as an optimal ERKi partner for synergistic combination with other MAPK pathway-targeted therapies. A clinical study evaluating D3S-002 in combination with D3S-001 for the treatment of patients with KRAS G12C-mutant NSCLC is currently underway."

First-in-human • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Safety and efficacy of Elisrasib (D3S-001), a next generation GDP-bound KRAS G12C inhibitor, as monotherapy or combination therapy with cetuximab in previously treated metastatic CRC and PDAC: Results from a phase 1/2 study (AACR 2026) - P1/2 | "Elisrasib with or without cetuximab has demonstrated promising efficacy and favorable tolerability in pts of 2L+ CRC and PDAC naïve to G12Ci."

Clinical • Combination therapy • Metastases • Monotherapy • P1/2 data • Oncology • EGFR • KRAS

Elisrasib Elicits Clinical Benefit in KRASG12C-mutant NSCLC. (PubMed, Cancer Discov) - "In a phase I/II clinical trial, patients with locally advanced or metastatic KRAS G12C-mutant non-small cell lung cancer treated with the next-generation KRASG12C inhibitor elisrasib showed robust and durable clinical responses. Patients naïve to KRASG12C inhibitors, as well as those refractory to other such drugs, experienced high rates of disease control-98.5% and 83.9%, respectively."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Elisrasib, a next-generation KRAS G12C inhibitor, demonstrated disease control in a majority of patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC), whether exposed to a prior KRAS G12C inhibitor or not, according to findings from an ongoing phase I/II clinical trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 (THE ASCO POST) - "Among patients who were not exposed to a prior KRAS G12C inhibitor (n = 84 evaluable patients), the objective response rate was 57.1%, including one complete response; the disease control rate was 98.8%. The median progression-free survival was 8.8 months and the median duration of response was 12.5 months. At 12 months, the overall survival rate was 67%. At the chosen expansion cohort dose (n = 68 evaluable patients), the objective response rate was 55.9%, with one complete response; the disease control rate was 98.5%. The median progression-free survival was 11.8 months, and the median duration of response was 14.9 months. At 12 months, the overall survival rate was 71%."

P1/2 data • Non Small Cell Lung Cancer

D3S-001, a second-generation GDP-bound KRAS G12C inhibitor, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities (AACR 2024) - P1/2 | "First-generation KRAS G12C inhibitors [G12Ci(s)], such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. Response rate and duration are reported in a companion clinical trial abstract submitted to this AACR meeting.In conclusion, D3S-001 is a second-generation GDP-bound KRAS G12Ci that overcomes GDP-to-GTP cycling. Its high covalent efficiency and rapid TE kinetics correlated with robust anti-tumor activity preclinically and translated into promising clinical activity with a high response rate and durable responses in a phase 1 trial."

First-in-human • Preclinical • Oncology • Solid Tumor • KRAS

A phase 1 study of D3S-001, a second-generation GDP-bound KRAS G12C inhibitor, as monotherapy in patients with KRAS G12C-mutated solid tumors (AACR 2024) - P1/2 | "D3S-001, a 2G G12Ci, is well tolerated and delivers promising anti-tumor activity in pts with NSCLC, CRC, and PDAC carrying KRAS G12C mutation across all dose levels in FIH trial."

Clinical • First-in-human • Monotherapy • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A Phase 1 Study to Assess Food Effect on the Pharmacokinetics of D3S-001 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: D3 Bio (Wuxi) Co., Ltd | Recruiting ➔ Completed | N=14 ➔ 26

Enrollment change • Trial completion

D3 Bio to Showcase Its Innovative KRAS Pipeline at AACR 2026, Including an Oral Presentation at Clinical Plenary Session (PRNewswire) - "'These presentations will showcase our comprehensive KRAS pipeline, including Elisrasib (D3S-001), our next-generation KRAS G12C inhibitor, D3S-002, a selective ERK1/2 inhibitor designed with a unique profile for combination strategies to enhance clinical efficacy and overcome resistance to KRAS G12C inhibitors; and D3S-003, our differentiated KRAS G12D inhibitor addressing large unmet medical needs in pancreatic and colo-rectal cancers. These data highlight D3 Bio's strong scientific progress and commitment to advancing transformative therapies for patients with KRAS-driven cancers'."

Clinical data • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

Therapeutic advances with KRASG12C inhibitors and combination strategies in non-small cell lung cancer brain metastases. (PubMed, Cancer Gene Ther) - "This article examines the clinical and translational application of specific next-generation blood-brain barrier penetrant KRASG12C inhibitors, such as sotorasib, adagrasib, olomorasib, RMC-6236, and D3S-001, and their rational integration with radiation therapy, targeted therapies, and immunotherapies to overcome therapeutic resistance in patients with NSCLC brain metastases. This review summarizes recent advances aimed at enhancing intracranial tumor control and overall survival in patients with NSCLC brain metastases through the use of next-generation KRASG12C inhibitors and multimodal therapies."

IO biomarker • Journal • Review • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

D3 Bio Receives U.S. FDA Clearance for Two IND Applications, Enabling Phase 1 Trial of D3S‑003 and Phase 2 Combination Study of Elisrasib (D3S‑001) with D3S‑002 (PRNewswire) - "With FDA clearance received, D3 Bio will advance D3S‑003 into a Phase 1 first‑in‑human study in patients with advanced solid tumors harboring KRAS G12D mutations. The newly cleared Phase 2 study will evaluate the combination of D3S‑001 and D3S‑002 in patients with KRAS G12C–mutant non‑small cell lung cancer (NSCLC) who have progressed on prior KRAS G12C‑targeted therapies. The trial, expected to begin in the first half of 2026..."

IND • New trial • Non Small Cell Lung Cancer

A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov) - P1/2 | N=67 | Active, not recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd | Phase classification: P1 ➔ P1/2 | Trial completion date: Nov 2025 ➔ Apr 2028 | Trial primary completion date: Nov 2025 ➔ Apr 2028

Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Solid Tumor

D3 Bio Secures $108 Million in Series B Financing to Advance Global Clinical Programs (PRNewswire) - "Proceeds from this financing will primarily support the planned global Phase III pivotal program for the company's lead asset, elisrasib (D3S-001). These pivotal trials will assess elisrasib as both a monotherapy and in combination therapies for KRAS G12C-mutant cancers across key countries and regions, including the United States, China, and the European Union, to facilitate global regulatory submissions. Furthermore, the funding will facilitate ongoing development of D3 Bio's comprehensive pipeline of targeted and immuno-oncology programs, which are centred on innovative mechanisms with first-in-class or best-in-class potential."

Financing • Solid Tumor

D3 Bio, Inc. Announces FDA…Orphan Drug Designation for D3S-001 for the Treatment of Patients with KRAS G12C-Mutated Cancers (PRNewswire) - "Orphan Drug Designation was granted for treatment of colorectal cancer (CRC) harboring KRAS G12C mutant protein....Orphan Drug Designations are based on clinical data from an ongoing Phase 1/2 study (NCT05410145)..."

Orphan drug • Colorectal Cancer

A Phase 1 Study to Assess Food Effect on the Pharmacokinetics of D3S-001 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd

New P1 trial

D3 Bio, Inc. Announces FDA Breakthrough Therapy Designation…for D3S-001 for the Treatment of Patients with KRAS G12C-Mutated Cancers (PRNewswire) - "Breakthrough Therapy Designation was granted for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have had prior treatment with platinum-based chemotherapy and anti-PD-(L)1 antibody but have not been previously treated with a KRAS G12C inhibitor...The Breakthrough Therapy....based on clinical data from an ongoing Phase 1/2 study (NCT05410145)..."

Breakthrough therapy • Evidence highlight • Non Small Cell Lung Cancer • KRAS