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

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

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

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

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

Glecirasib Combined With Ivonescimab for First-line Treatment of KRAS G12C-mutated NSCLC (clinicaltrials.gov) - P1/2 | N=42 | Not yet recruiting | Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

JAB-21822 Activity in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=29 | Completed | Sponsor: Jacobio Pharmaceuticals Co., Ltd. | Recruiting ➔ Completed | N=100 ➔ 29 | Trial completion date: Jul 2025 ➔ Feb 2025 | Trial primary completion date: Jan 2024 ➔ Feb 2025

Enrollment change • Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

JAB-21822 Combined With Chemotherapy and Bevacizumab in Second-line KRAS G12C CRC (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Jian Li | Recruiting ➔ Active, not recruiting | Phase classification: P2 ➔ P1 | Trial primary completion date: Jun 2026 ➔ Mar 2026

Enrollment closed • Phase classification • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • KRAS

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

Jacobio combo delivers 71% ORR, sets stage for first SHP-2–based NSCLC therapy (Indian Pharma Post) - "The regimen pairs glecirasib, a KRAS G12C inhibitor, with sitneprotafib, an SHP-2 inhibitor, aiming to offer a fully oral, chemotherapy-free option for patients with KRAS G12C-mutated NSCLC."

P1/2 data • Non Small Cell Lung Cancer

Advances in Diagnosis and Targeted Therapy of KRASG12C Mutant Non-small Cell Lung Cancer (PubMed, Zhongguo Fei Ai Za Zhi) - "In targeted therapies, KRASG12C targeted drugs, including Sotorasib, Adagrasib, Fulzerasib, Garsorasib, and Glecirasib, have demonstrated certain therapeutic efficacies in clinical trials and have obtained marketing approval. To tackle drug resistance and enhance patient's prognoses, combination therapeutic strategies that integrate targeted agents with chemotherapy, immune checkpoint inhibitors, Src homology region 2 domain-containing phosphatase 2 (SHP2) inhibitors, and epidermal growth factor receptor (EGFR) monoclonal antibodies have emerged. This paper systematically reviews the advancements in the diagnosis and targeted therapy of NSCLC with KRASG12C mutation, aiming to offer a reference for the selection of clinical treatment regimens and subsequent research.."

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

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

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

Glecirasib (JAB-21822, KRAS G12C inhibitor) (PRNewswire) - "Phase I/II data for the combination with SHP2 inhibitor has been accepted by a top-tier academic journal, with publication expected in H2 2025."

P1/2 data • Solid Tumor

A Phase II Study Evaluating JAB-21822 Monotherapy in Adult Patients With Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation. (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial completion date: Nov 2025 ➔ Dec 2027 | Trial primary completion date: May 2025 ➔ Dec 2026

Monotherapy • Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9 • KRAS • MSI

Jacobio’s KRAS G12C Inhibitor Glecirasib Approved for Market Launch (Jacobio Press Release) - "According to the official website of the National Medical Products Administration (NMPA), Jacobio Pharma...has received approval for its independently developed KRAS G12C inhibitor, glecirasib, to be launched on the market. The approved indication is for patients with non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations who have received at least one prior systemic therapy. This approval triggers a milestone payment from Jacobio’s partner Shanghai Allist Pharmaceuticals Co., Ltd. (688578.SH), and Jacobio will receive a milestone payment of RMB 50 million."

China approval • Non Small Cell Lung Cancer

Glecirasib, a potent and selective covalent KRAS G12C inhibitor exhibiting synergism with cetuximab or SHP2 inhibitor JAB-3312. (PubMed, Cancer Res Commun) - P1/2, P3 | "Glecirasib could effectively inhibit HRAS G12C, NRAS G12C, and several G12C-inclusive KRAS double mutants that showed resistance to adagrasib. A new drug application for glecirasib has been submitted in China, seeking approval for the treatment of non-small cell lung cancer, supported by a pivotal phase 2 single-arm study (NCT05009329). Additionally, glecirasib is being explored in clinical trials in combination with cetuximab (phase 2, NCT05194995) and JAB-3312 (phase 3, NCT06416410)."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HRAS • KRAS • NRAS

JAB-3312, a Potent Allosteric SHP2 Inhibitor that Enhances the Efficacy of RTK/RAS/MAPK and PD-1 Blockade Therapies. (PubMed, Clin Cancer Res) - P1/2 | "JAB-3312 in combination with RTK/RAS/MAPK or PD-1 blockage therapies is a promising strategy that warrants further clinical investigation."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • 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 primary completion date: Dec 2023 ➔ Feb 2026

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

ABBISKO THERAPEUTICS AND ALLIST ENTER INTO A COOPERATION AGREEMENT TO EXPLORE ABSK043 IN COMBINATION GLECIRASIB FOR THE TREATMENT OF NSCLC (HKEXnews) - "...Abbisko Therapeutics...announced that it has entered into a cooperation agreement with Shanghai Allist Pharmaceuticals...to explore the combination of Abbisko Therapeutics’ investigational oral PD-L1 inhibitor, ABSK043, with Allist’s KRAS-G12C inhibitor, glecirasib, for the treatment of non-small cell lung cancer patients with KRAS-G12C mutation."

Licensing / partnership • Non Small Cell Lung Cancer

Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer: a phase 2b trial. (PubMed, Nat Med) - P1/2 | "Glecirasib exhibited promising clinical efficacy and manageable safety profiles in these patient populations. ClinicalTrials.gov identifier: NCT05009329 ."

Journal • P2b 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. | N=124 ➔ 240

Enrollment change • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Jacobio Pharma Announces 2024 Annual Results (PRNewswire) - "Non-small cell lung cancer (NSCLC): Glecirasib is expected to be approved in the first half of 2025; Multi-tumor basket: The multi-tumor basket registration phase II trial of glecirasib for the treatment of pancreatic cancer, biliary tract cancer, gastric cancer, small bowel cancer, appendiceal cancer and other indications has been initiated in China."

China approval • Trial status • Appendix Cancer • Biliary Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer • Small Intestinal Carcinoma

JAB-21822 in Combination with Cetuximab in Patients with Advanced CRC and Other Solid Tumors with KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=48 | Active, not recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Appendix Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Small Intestinal Carcinoma • Solid Tumor • KRAS

Small molecules for Kirsten rat sarcoma viral oncogene homolog mutant cancers: Past, present, and future. (PubMed, Eur J Pharmacol) - "However, due to the lack of a binding pocket, KRAS has long been considered an undruggable target in recent decades until the discovery of Sotorasib (AMG510). With the approval of Glecirasib (JAB-21822), there are three approved small molecule inhibitors of KRAS, all of which are KRAS G12C inhibitors. At the same time, the limited clinical benefits and rapid emergence of drug resistance to the approved inhibitors have also promoted the emergence of more therapeutics, such as tri-complexes and proteolysis-targeting chimeras (PROTAC). In this paper, we summarize the development of KRAS inhibitors (KRASG12C, KRASG12D, and KRASmulti inhibitors, PROTAC, and tri-complex) and discuss the challenges and opportunities in the discovery of KRAS inhibitors in the hope of providing insights into the development of novel medications for KRAS."

Journal • Preclinical • Review • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • EGFR • KRAS • mTOR