Airuikai (glecirasib) / Jacobio Pharma, Allist - LARVOL DELTA

Glecirasib with or without cetuximab in previously treated locally advanced or metastatic colorectal cancer with KRASG12C mutation (JAB-21822-1002 and JAB-21822-1007): two open-label, non-randomised phase 1/2 trials. (PubMed, Lancet Gastroenterol Hepatol) - P1/2 | "Glecirasib monotherapy and its combination with cetuximab represent potential treatment options for patients with advanced, refractory colorectal cancer harbouring KRASG12C mutations. The promising efficacy and safety support further exploration of glecirasib-based combinations in earlier lines of treatment."

Journal • P1/2 data • Appendix Cancer • Cardiovascular • Colorectal Cancer • Febrile Neutropenia • Hematological Disorders • Interstitial Lung Disease • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • KRAS

A Prospective Single-Arm Phase II Clinical Study of Glecirasib Combined with Sacituzumab Tirumotecan as Second-Line Therapy for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring KRAS G12C Mutation (ChiCTR) - P4 | N=48 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital; Peking Union Medical College Hospital

New P4 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study of BL-B01D1 Combined With Glecirasib in Patients With KRAS G12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

KRAS-Targeted Therapies in NSCLC: Resistance, Combination Strategies, and Emerging Clinical Paradigms. (PubMed, Med Oncol) - "Sotorasib and adagrasib achieve ORRs of 37-43% and median PFS ~ 6-7 months in previously treated KRAS G12C NSCLC, with improved tolerability over docetaxel. Next-generation inhibitors (olomorasib, divarasib, glecirasib, D-1553, IBI351) demonstrate ORRs 45-55% and, in some studies, PFS exceeding first-generation agents, while emerging KRAS G12D inhibitors show early proof-of-concept activity...KRAS-mutant NSCLC is transitioning from historically untargetable disease to a therapeutically actionable subset. Future progress hinges on resistance-directed combinations, biomarker-guided personalization, expansion to non-G12C mutants, and evaluation in earlier disease settings."

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

Glecirasib plus sitneprotafib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 1/2a trial. (PubMed, Lancet Respir Med) - P1/2 | "Glecirasib combined with sitneprotafib showed promising efficacy and manageable safety in patients with advanced KRASG12C -mutated NSCLC, particularly among those who had not received previous treatment. These findings support the evaluation of this combination in a phase 3 trial comparing this chemotherapy-free regimen to current standard of care in this patient group."

Journal • P1/2 data • Dyslipidemia • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • KRAS

Genomic Biomarkers for Whole-Process Stratification in KRASG12C-Mutant NSCLC: A Phase 1/2 Trial Analysis of Glecirasib Plus Sitneprotafib (IASLC-WCLC 2026) - P1/2 | "Additionally, treatment-related hepatic adverse events correlated with improved survival, and the HLA-A*11:01 allele was identified as a host genetic protective factor against such hepatotoxicity, mediated by enhanced M2 macrophage polarization and TGFB1-TGFBR2 pathway activity that attenuates hepatic inflammation. Conclusions : Our findings first of all establish a novel molecular framework for precision management of KRASG12C-mutant NSCLC treated with glecirasib plus sitneprotafib, wherein baseline genomic signature stratification and dynamic single-gene KRASG12C ctDNA monitoring enable risk-adapted clinical decision-making, early efficacy assessment and identification of resistance.$$graphic_{02101649-137C-486C-8C2E-ABAF5D5FD3DA}$$"

Biomarker • P1/2 data • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • KRAS • PTPN11 • SMAD4 • SMARCA4 • SMARCB1 • TGFB1 • TGFBR2

Efficacy and safety of glecirasib in solid tumors with KRAS G12C mutation: A pooled analysis of two phase I/II trials. (PubMed, Cancer Commun (Lond)) - P1/2 | "Glecirasib showed promising efficacy and was well tolerated in patients with PDAC and other advanced solid tumors (beyond NSCLC and CRC), warranting further expedited clinical development in this patient population."

Journal • P1/2 data • Retrospective data • Appendix Cancer • Biliary Cancer • Biliary Tract Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Small Intestinal Carcinoma • Solid Tumor • KRAS

Glecirasib (KRAS G12C inhibitor) in combination with JAB-3312 (SHP2 inhibitor) in patients with KRAS p.G12C mutated solid tumors (ESMO 2023) - P1/2 | "Conclusions Glecirasib plus JAB-3312 was well tolerated with promising efficacy in KRAS p.G12C NSCLC. Currently, dose expansion is underway to further evaluate efficacy and safety."

Clinical • Combination therapy • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Genomic Biomarkers for Whole-Process Stratification in KRASG12C-Mutant NSCLC: A Phase 1/2 Trial Analysis of Glecirasib Plus Sitneprotafib (IASLC-WCLC 2026) - P1/2 | "Additionally, treatment-related hepatic adverse events correlated with improved survival, and the HLA-A*11:01 allele was identified as a host genetic protective factor against such hepatotoxicity, mediated by enhanced M2 macrophage polarization and TGFB1-TGFBR2 pathway activity that attenuates hepatic inflammation. Conclusions : Our findings first of all establish a novel molecular framework for precision management of KRASG12C-mutant NSCLC treated with glecirasib plus sitneprotafib, wherein baseline genomic signature stratification and dynamic single-gene KRASG12C ctDNA monitoring enable risk-adapted clinical decision-making, early efficacy assessment and identification of resistance."

Biomarker • P1/2 data • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • KRAS • PTPN11 • SMAD4 • SMARCA4 • SMARCB1 • TGFB1 • TGFBR2

Updated safety and efficacy data of combined KRAS G12C inhibitor (glecirasib, JAB-21822) and SHP2 inhibitor (JAB-3312) in patients with KRAS p.G12C mutated solid tumors. (ASCO 2024) - P1/2 | "Glecirasib plus JAB-3312 has a manageable safety profile and a promising ORR and PFS as a front-line treatment for patients with KRAS p.G12C NSCLC. This combination will be further evaluated in a randomized phase III trial in NSCLC."

Clinical • Anemia • Colorectal Cancer • Dyslipidemia • Gastrointestinal Cancer • Hematological Disorders • Hypertriglyceridemia • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Preliminary activity and safety results of KRAS G12C inhibitor glecirasib (JAB-21822) in patients with pancreatic cancer and other solid tumors. (ASCO-GI 2024) - P1/2, P2 | "Glecirasib monotherapy is well tolerated and has a manageable safety profile and exhibits promising anti-tumor activity in pts with KRAS G12C mutated PDAC and other solid tumors. Further clinical development of glecirasib in above mentioned population is ongoing (NCT06008288). Clinical trial information: NCT05009329 and NCT05002270."

Clinical • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A pivotal phase 2 single-arm study of glecirasib (JAB-21822) in patients with NSCLC harboring KRAS G12C mutation. (ASCO Plenary Apr 2024) - No abstract available

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

JAB-21822-1006: Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A Study of JAB-21822 in Adult Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation in China (clinicaltrials.gov) - P1/2 | N=315 | Active, not recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial primary completion date: May 2026 ➔ Aug 2026

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

JAB-21822 3002: JAB-21822 Combined With JAB-3312 Compared SOC in the First Line for Treatment of Advanced Non-small Cell Lung Cancer With KRAS p.G12C Mutation (clinicaltrials.gov) - P3 | N=392 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial completion date: Feb 2027 ➔ Aug 2030 | Trial primary completion date: Sep 2026 ➔ Sep 2029

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1 (clinicaltrials.gov) - P1/2 | N=104 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial completion date: Feb 2026 ➔ Aug 2027 | Trial primary completion date: Feb 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KEAP1 • KRAS • STK11

KRAS G12C-Targeted Therapy in Non-Small Cell Lung Cancer: From Resistant Salvage to Potential First-Line Backbone. (PubMed, Int J Mol Sci) - "The discovery of a cryptic binding pocket accessible in the GDP-bound state enabled covalent inhibitors-sotorasib and adagrasib-that have received regulatory approval for previously treated KRAS G12C-mutant NSCLC, with sotorasib demonstrating PFS and OS superiority over docetaxel in CodeBreaK 200 and adagrasib showing meaningful intracranial activity and a progression-free survival benefit over docetaxel in KRYSTAL-12...Next-generation covalent inhibitors (divarasib, glecirasib, olomorasib), tri-complex RAS(ON) inhibitors (RMC-6291), pan-KRAS agents, and rationally designed combinations with EGFR, SHP2, SOS1, and PD-1 inhibitors are repositioning KRAS-directed therapy toward earlier lines of treatment. This review integrates the structural, signaling, and clinical biology of KRAS G12C with contemporary trial and real-world evidence to examine the emerging case for first-line KRAS G12C inhibition in genomically defined subsets of NSCLC. First-line use nonetheless remains..."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KEAP1 • KRAS • STK11 • TP53

Therapeutic Strategies Targeting the KRAS G12C Mutation-Current Landscape and Future Directions (PubMed, Gan To Kagaku Ryoho) - "First-generation KRAS G12C inhibitors, including sotorasib and adagrasib, have demonstrated clinically meaningful activity in previously treated NSCLC; however, their benefit is limited by acquired resistance, which arises through secondary KRAS alterations, bypass pathway activation, and adaptive reactivation of downstream MAPK signaling...Multiple next-generation KRAS G12C inhibitors, such as divarasib, glecirasib, and olomorasib, are currently under clinical development, with early evidence suggesting improved potency, selectivity, and tolerability...More recently, the advent of RAS (ON) inhibitors, exemplified by daraxonrasib (RMC-6236), has introduced a distinct therapeutic paradigm by directly targeting active RAS through a tri-complex mechanism. As the therapeutic landscape continues to evolve, optimal treatment selection will require integrated consideration of molecular heterogeneity, resistance mechanisms, toxicity profiles, and patient-centered shared..."

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

The dynamic evolution of circulating tumor cells during glecirasib treatment predicts survival and resistance in gastrointestinal tumors with KRASG12C mutation. (PubMed, Hum Cell) - P1/2 | "E/M-CTC ≤ 1 showed a trend toward improved OS (p = 0.086). In addition, patients with > 1 CTC who received local radiotherapy for progressive lesions after glecirasib targeted therapy had significantly prolonged PFS and OS compared to those who did not (p < 0.05)."

Circulating tumor cells • Journal • Oncology • Solid Tumor • CTCs • KRAS

A Phase 2 Clinical Study of Combination Therapy With ABSK043 and Glecirasib (clinicaltrials.gov) - P2 | N=86 | Recruiting | Sponsor: Abbisko Therapeutics Co, Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

Trends in historical response rates: A meta-analysis of KRAS G12C inhibitors in pretreated metastatic pancreatic cancer—Effects on ORR and disease control. (ASCO 2026) - "The development of covalent KRAS G12C inhibitors—including sotorasib, adagrasib, garsorasib, glecirasib, and divarasib—has opened new therapeutic options for this molecularly defined subset of PDAC patients. KRAS G12C inhibitor monotherapy demonstrates clinically significant and durable efficacy in pretreated adults with advanced/metastatic PDAC harboring the KRAS G12C mutation. The pooled ORR of approximately one-third, together with a DCR near 90%, indicates substantial tumor control in a population with historically poor outcomes. Median PFS of approximately 5 months and OS of nearly 9 months represent clinically relevant improvements over standard salvage therapies, supporting KRAS G12C inhibitors as a viable option after chemotherapy failure."

Metastases • Retrospective data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

A phase Ib, open-label, clinical trial of JAB21822 combined with second-line chemotherapy for metastatic colorectal cancer with KRAS G12C mutation. (ASCO 2026) - P1 | "Clinical Trial Registration Number: NCT06838338 Background: Glecirasib (JAB-21822), a novel, covalent, small molecule KRAS G12C-GDP covalent inhibitor, has been shown to be effective and safe as monotherapy or in combination with cetuximab in treating patients with refractory, unresectable locally advanced or metastatic colorectal cancer (mCRC) harboring KRAS G12C mutation... Patients (pts) with mCRC harboring KRAS G12C mutation were enrolled and treated with glecirasib (800mg QD) combined with standard second-line chemotherapy (FOLFIRI or FOLFOX) and bevacizumab until disease progression or intolerable toxicity or patient-initiated withdrawal from the study... Glecirasib in combination with the second-line standard chemotherapy and bevacizumab demonstrated encouraging efficacy and tolerable safety in the second-line treatment of mCRC patients with KRAS G12C mutation."

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor • KRAS

A Trial of HRS-7058 in Advanced or Metastatic Non-Small Cell Lung Cancer Patients Who Have Failed Standard Treatment (clinicaltrials.gov) - P3 | N=450 | Not yet recruiting | Sponsor: Shandong Suncadia Medicine Co., Ltd.

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Non-small cell lung cancer research: advances and persistent challenges. (PubMed, Front Oncol) - "Recent innovations include antibody-drug conjugates (ADCs) such as TROP-2-targeting agents and HER3-DXd, which show promising efficacy in refractory disease. Next-generation tyrosine kinase inhibitors (TKIs), including lorlatinib, tepotinib, and glecirasib, have shown improved outcomes for patients with oncogene-driven NSCLC...Future efforts must prioritize overcoming resistance through combination strategies and ADCs, validating biomarkers using AI and ctDNA, streamlining CGP implementation, and addressing the unique needs of special populations. Bridging these biological and systemic challenges is essential for improving survival outcomes and ensuring equitable benefits for all NSCLC patients."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • KEAP1 • STK11

A Study of JAB-21822 in Adult Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation in China (clinicaltrials.gov) - P1/2 | N=315 | Active, not recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS