Anfangning (garsorasib) / InventisBio, Sino Biopharm - LARVOL DELTA

Efficacy and safety of garsorasib in patients with KRAS G12C-mutated advanced pancreatic cancer. (PubMed, Br J Cancer) - P1/2 | "Garsorasib demonstrated encouraging antitumor activity and a tolerable safety profile in patients with KRAS G12C-mutated advanced pancreatic cancer."

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

Garsorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: A pooled analysis of phase 1/2 study. (PubMed, Eur J Cancer) - P1/2 | "This pooled analysis confirmed the robust efficacy and manageable safety of garsorasib in KRAS G12C-mutated NSCLC."

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

Garsorasib in Patients with KRAS G12C-Mutated Non-Small-Cell Lung Cancer: A Pooled Analysis of Phase 1/2 Study (Eur J Cancer) - "This pooled dataset included 189 patients (N=66 in phase 1 and N=123 in phase 2). The median pooled follow-up time was 13.0 months (IQR: 6.7-17.5). The objective response rate was 48.1% (95%CI: 40.8-55.5), and disease control rate was 87.8% (95%CI: 82.3-92.1). The median duration of response was 12.45 months (95% CI: 8.31, 14.49), the median progression-free survival was 9.07 months (95%CI: 7.39-9.76), and the median overall survival was 14.19 months (95%CI: 13.08-17.54)."

P1/2 data • Non Small Cell Lung Cancer

Case Report: Two cases of long-term survival in advanced pancreatic cancer patients following treatment with KRAS G12C inhibitors. (PubMed, Front Oncol) - "In this report, we present two patients with advanced PDAC with KRAS G12C mutations who achieved remarkable disease control and prolonged survival following treatment with the KRAS G12C inhibitor D1553 (garsorasib)...Case 2, a 75-year-old woman initially treated with Folinic acid, fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) and stereotactic body radiotherapy (SBRT), demonstrated sustained disease stability for over three years on KRAS G12C inhibitor therapy...These cases underscore the potential of KRAS-directed therapies in PDAC and illustrate the importance of molecular profiling in identifying eligible patients. The findings support further investigation into the durability of KRAS G12C inhibition, resistance mechanisms, and combination treatment strategies to optimize patient outcomes."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Galaxy-L-01: A Multicenter, Prospective Clinical Study Evaluating the Garsorasib Plus Anlotinib as First-Line Therapy for KRAS G12C-Mutant Advanced Non-Squamous NSCLC (ChiCTR) - P4 | N=104 | Not yet recruiting | Sponsor: Shanghai Chest Hospital; Shanghai Chest Hospital

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

Phase II study of Garsorasib for the adjuvant treatment of KRAS G12C-mutated NSCLC (ChiCTR) - P2 | N=30 | Not yet recruiting | Sponsor: Shanghai Pulmonary Hospital; Shanghai Pulmonary Hospital

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

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 3 Study of IN10018 in Combination With D-1553 Versus Standard Therapy for First Line Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: InxMed (Shanghai) Co., Ltd.

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

Literature review of advances and challenges in KRAS G12C mutant non-small cell lung cancer. (PubMed, Transl Lung Cancer Res) - "The KRAS G12C mutation was once considered "undruggable" until the breakthrough approval of two targeted inhibitors: AMG510 (sotorasib) and MRTX849 (adagrasib). In China, IBI351 and D-1553 have also been approved for the treatment of adult patients with advanced NSCLC harboring the KRAS G12C mutation...Notably, recent findings indicate that combining dual immune checkpoint inhibitors (ICIs; durvalumab and tremelimumab) with chemotherapy (CT) in patients with advanced NSCLC, including those with KRAS mutations, can result in durable survival benefits...Moreover, the POSEIDON trial has highlighted the potential of dual ICI therapy combined with CT to achieve sustained clinical benefits. Despite these advances, the heterogeneity of tumor responses underscores the need for further investigation into intrinsic resistance mechanisms and the strategic optimization of combination therapies to enhance treatment outcomes."

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

The objective response rate doubled over that of garsorasib in the treatment of colorectal cancer and won the STTT [Google translation] (Sino Biopharm Press Release) - P1/2 | N=180 | NCT04585035 | Sponsor: InventisBio Co., Ltd | "Recently, the research results of garsorasib...were published in the internationally renowned journal Signal Transduction and Targeted Therapy....Since the first patient was enrolled in November 2021, as of February 29, 2024, a total of 26 patients with locally advanced or metastatic CRC were enrolled in the study to receive garsorasib monotherapy, and 42 patients with locally advanced or metastatic CRC were treated with garsorasib combined with cetuximab. The confirmed ORR and DCR were 45.2% (95% CI, 29.8–61.3) and 92.9% (95% CI, 80.5–98.5), respectively. The median progression-free survival (PFS) was 7.5 months (95% CI, 5.5–8.1). At the time of data cutoff, the median OS had not yet been reached (95% CI, 11.3–NE). Most of the treatment-related adverse events (TRAEs) in the study were grade 1-2."

P2 data • Colorectal Cancer

Garsorasib, a KRAS G12C inhibitor, with or without cetuximab, an EGFR antibody, in colorectal cancer cohorts of a phase II trial in advanced solid tumors with KRAS G12C mutation. (PubMed, Signal Transduct Target Ther) - P1/2 | "Grade ≥3 treatment-related adverse events occurred in 5 (19.2%) and 6 (14.3%) patients in monotherapy and combination cohort, respectively. Garsorasib with or without cetuximab showed a promising efficacy and manageable safety profiles in heavily pretreated patients with KRAS G12C-mutated CRC, providing a potential new treatment approach for such population."

Journal • P2 data • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Efficacy and safety of KRAS p.G12C inhibitors in advanced NSCLC: A systematic review and meta-analysis. (ASCO 2025) - "The KRAS p.G12C inhibitors evaluated were sotorasib, adagrasib, divarasib, and garsorasib. This meta-analysis underscores the favorable safety and efficacy profiles of KRAS p.G12C inhibitors after first-line progression in advanced NSCLC, despite the frequent adverse events, which were considered manageable. Further randomized controlled trials are expected to confirm these results and refine their role in subgroup populations, including STK1 and KEAP1 co-mutations, that confer even poor prognosis."

Metastases • Retrospective data • Review • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKB • CDK7 • KEAP1 • KRAS

Safety and efficacy of ifebemtinib (IN10018) combined with garsorasib (D-1553) in KRAS G12C mutant solid tumors from a phase Ib/II study: Results from single-arm of non-small-cell lung cancer (NSCLC) and randomized part of colorectal cancer (CRC). (ASCO 2025) - P1/2 | "Combination of ifebe and D-1553, as a dual-oral regimen, is safe and highly efficacious against KRAS G12C mutant NSCLC with ORR over 90% and durable efficacy. Preliminary results from the randomized part of CRC demonstrated ORR doubling with the combo, validating the add-on benefits of ifebe. Our data suggest that ifebe could be an ideal partner of RASi."

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

An overview of PROTACs targeting KRAS and SOS1 as antitumor agents. (PubMed, Bioorg Med Chem Lett) - "Currently, four KRASG12C-specific inhibitors, namely sotorasib, adagrasib, fulzerasib and garsorasib, have garnered regulatory approval. PROTAC-mediated KRAS and SOS1 degradation has been emerged as a promising strategy to overcome these issues, and achieved rapid progress in the recent years. This article provides an overview of the chemical structures, design strategies, structure-activity relationship (SAR) studies as well as in vitro and in vivo activities of the PROTACs degrading KRAS and SOS1, and sheds light on future challenges and opportunities to accelerate the development of new chemotherapies for KRAS-driven cancers."

Journal • Review • Oncology • Targeted Protein Degradation • KRAS

Potency and Safety of KRAS G12C Inhibitors in Solid Tumors: A Systematic Review. (PubMed, Clin Med Insights Oncol) - "In this study, we comprehensively evaluate the effectiveness and toxicity of relevant KRAS G12C inhibitors (Sotorasib, Adagrasib, Garsorasib, and Divarasib) in patients with colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), and pancreatic ductal adenocarcinomas (PDAC). However, Adagrasib and Sotorasib are moderately efficient in CRC clinical trials. This study confirms that patients treated with these KRAS G12C inhibitors, exclusively or combined with conventional therapies, achieve better treatment responses and modulate the progressions of these solid tumors."

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

Study to Evaluate D-1553 in Combination With IN10018 in Subjects With Solid Tumors (clinicaltrials.gov) - P1/2 | N=92 | Active, not recruiting | Sponsor: InventisBio Co., Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KEYNOTE-C15: Study to Evaluate D-1553 in Subjects With Solid Tumors (clinicaltrials.gov) - P1/2 | N=180 | Active, not recruiting | Sponsor: InventisBio Co., Ltd | Trial completion date: Feb 2025 ➔ Dec 2025

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

Effect of Food on the Pharmacokinetic Characteristics of a Single Oral Dose of D-1553, a Selective Inhibitor of KRASG12C, in Healthy Chinese Subjects. (PubMed, Clin Drug Investig) - "The study indicated that a high-calorie and high-fat meal has no clinically relevant impact on the PK and bioavailability of D-1553 in healthy Chinese subjects. D-1553 was generally safe and well-tolerated under both fasting and fed conditions. The findings suggest that D-1553 could be administered orally with or without food."

Journal • PK/PD data • KRAS

Garsorasib Tablets Approved with Conditions for Marketing by China NMPA - "Recently, the Class 1 innovative drug Garsorasib Tablets...of Shanghai Chia-tai Tianqing Pharmaceutical Technology Development Co. Ltd. is approved with conditions for marketing through the priority review and approval procedure by NMPA in China. This drug is indicated for adult patients with advanced non-small cell lung cancer (NSCLC) carrying the Kirsten rat sarcoma viral oncogene (KRAS) G12C mutation who have received at least one systemic treatment, providing a new treatment option for patients."

China approval • Non Small Cell Lung Cancer

InxMed FAK Inhibitor Ifebemtinib Received Breakthrough Therapy Designation by China National Medical Products Administration for First-Line Non-Small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation (PRNewswire) - "InxMed...announced that China National Medical Products Administration (NMPA) has granted Ifebemtinib (IN10018) Breakthrough Therapy designation (BTD) for the first-line (1L) treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutation in combination with garsorasib, a specific inhibitor of the KRAS G12C mutation. This is the second BTD ifebemtinib received....The BTD is supported by the data from the Phase Ib/II study evaluating the efficacy and safety of ifebemtinib in combination with garsorasib for the 1L treatment of NSCLC with KRAS G12C mutation (NCT06166836)....InxMed is currently conducting a registrational trial in platinum-resistant ovarian cancer in China, for which the company plans to submit a New Drug Application to the NMPA in 2025."

Breakthrough therapy • China filing • Evidence highlight • Non Small Cell Lung Cancer • Ovarian Cancer • KRAS

Study to Evaluate D-1553 in Combination With IN10018 in Subjects With Solid Tumors (clinicaltrials.gov) - P1/2 | N=92 | Recruiting | Sponsor: InventisBio Co., Ltd | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

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

Study to Evaluate D-1553 in Subjects With Lung Cancer (clinicaltrials.gov) - P1/2 | N=225 | Completed | Sponsor: InventisBio Co., Ltd | Active, not recruiting ➔ Completed

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

A Study to Evaluate D-1553 in Combination Therapy in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=22 | Terminated | Sponsor: InventisBio Co., Ltd | Phase classification: P1b/2 ➔ P1/2 | N=144 ➔ 22 | Trial completion date: Dec 2024 ➔ Jun 2024 | Recruiting ➔ Terminated; Adjustment of drug development strategy.

Combination therapy • Enrollment change • Metastases • Phase classification • Trial completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study to Evaluate the Effects of D-1553 on PK of Midazolam, Caffeine, Rosuvastatin, Furosemide, Digoxin, and Itraconazole or Omeprazole on PK of D-1553 (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: InventisBio Co., Ltd | Active, not recruiting ➔ Completed | Trial completion date: Jul 2024 ➔ Feb 2024

Trial completion • Trial completion date

Garsorasib in KRAS G12C-Mutated Non-Small-Cell Lung Cancer: Updated Results from a Phase 2 Study (IASLC-WCLC 2024) - P1/2 | "Conclusions : Garsorasib has shown a high tumor response rate and long duration of response in a pretreated population of patients with KRAS G12C-mutated NSCLC. After prolonged follow up, the updated PFS and OS suggest a long-term clinical benefit, which will be further evaluated in a randomized, double-blind, controlled trial."

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