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

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

Safety and efficacy of ifebemtinib (IN10018) combined with D-1553 in solid tumors with KRAS G12C mutation: Results from a phase Ib/II study (ESMO 2024) - P1/2 | "The combination of ifebemtinib and D-1553, as a dual-oral regimen, showed promising antitumor activity and manageable safety profile in KRAS G12C mutant solid tumors. Long term FU is needed to assess the potential of such novel combo."

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

Six innovative Chinese biopharmaceutical drugs were unveiled at the World Lung Cancer Conference to empower patients with treatment [Google translation] (Sohu.com) - "In 2025, several blockbuster products of Sino Biopharmaceuticals are expected to be approved for marketing. Among them, KRAS G12C inhibitor D-1553 is the first of its kind in China, and is expected to fill clinical and market gaps; CDK2/4/6 inhibitor TQB3616 is a new generation of therapy for HR+/HER- breast cancer, and is expected to become the best product of its kind; the first domestically launched pertuzumab biosimilar next year is expected to be combined with the already launched trastuzumab to form a 'trastuzumab' combination, which is expected to bring new hope to HER2-positive breast cancer patients."

Approval • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Innovent Biologics-U (688382): garsorasib is about to be launched and its R&D is progressing smoothly [Google translation] (Eastmoney.com) - "The company's KRAS G12C inhibitor garsorasib submitted its NDA in December 2023. According to the NMPA review task announcement, garsorasib is currently in the supplementary information review stage and is expected to be approved for marketing at the end of this year or early next year....In addition, 24H1 garsorasib's pancreatic ductal adenocarcinoma and colorectal cancer indications have been newly included in the breakthrough therapy drug program by the CDE, and clinical trials for other indications are progressing in an orderly manner: the Phase III clinical trial of monotherapy for second-line KRAS G12C mutant NSCLC has completed the enrollment of the first patient, and the clinical trial application for the treatment of advanced solid tumors with KRASG12C mutations in combination with SHP2 inhibitors has passed the CDE review."

Breakthrough therapy • China approval • Enrollment closed • New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Another KRAS Inhibitor Scores an Early Win in Advanced Non-Small Cell Lung Cancer (MedPageToday) - "'The results from the D1553-102 study group confirm the activity of [guanosine diphosphate]-bound KRASG12C inhibitors as a drug class,' wrote...Liza Villaruz, MD...'Furthermore, they provide supporting evidence of the modest benefit of garsorasib in KRASG12C-mutated NSCLC, similar to that provided by already-approved KRASG12C inhibitors. If the drug is ultimately approved, it could provide greater global access to an oral, targeted option for patients with KRASG12C-mutated NSCLC.'"

Media quote

Garsorasib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 2 trial. (PubMed, Lancet Respir Med) - P1/2 | "The results show that garsorasib has a high response rate, long duration of response, and an acceptable and manageable safety profile in patients with previously treated KRASG12C-mutated NSCLC. Garsorasib potentially provides a promising treatment option for this patient population."

IO biomarker • Journal • P2 data • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Safety and efficacy of ifebemtinib (IN10018) combined with D-1553 in non-small-cell lung cancer (NSCLC) with KRAS G12C mutation: Results from a phase Ib/II study. (ASCO 2024) - P1/2 | "The combination of ifebemtinib and D-1553, as a dual-oral regimen, showed promising antitumor activity and manageable safety profile in KRAS G12C mutant front-line NSCLC population. Long term follow-up is needed to assess the potential of such novel combo."

Clinical • P1/2 data • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • KRAS

GH21 Combined With D-1553 With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=126 | Not yet recruiting | Sponsor: Suzhou Genhouse Bio Co., Ltd.

Metastases • New P1/2 trial • Oncology • Solid Tumor • KRAS

InxMed Reports Positive Phase Ib/II Results for Ifebemtinib in Combination with Garsorasib in Non-Small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation (PRNewswire) - P1b/2 | N=140 | NCT06166836 | Sponsor: InxMed (Shanghai) Co., Ltd | "InxMed Co., Ltd...announced results from the Phase Ib/II clinical trial of ifebemtinib, the company's focal adhesion kinase (FAK) inhibitor, in combination with garsorasib, a specific inhibitor of the KRAS G12C mutation, for the first-line treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutation...The objective response rate (ORR) was 90.3% (95% CI: 74.3, 98.0), and the disease control rate (DCR) was 96.8% (95% CI: 83.3, 99.9). A total of 28 partial responses (PRs) and two stable diseases (SDs) were reported. Twenty-six out of 28 PRs were confirmed thus far...The overall safety profile of the combination of ifebemtinib with garsorasib is consistent with either ifebemtinib or garsorasib monotherapy....InxMed plans to submit a New Drug Application to the NMPA in early 2025."

China filing • P1/2 data • Non Small Cell Lung Cancer