HRS-4642 / Jiangsu Hengrui Pharma - LARVOL DELTA

KRAS G12D inhibitor HRS-4642 in patients with KRAS G12D-mutant advanced solid tumors: A phase I trial (ESMO 2025) - "These data support further investigation of HRS-4642, including in combination regimens. Legal entity responsible for the study Jiangsu Hengrui Pharmaceuticals, Co., Ltd."

Clinical • IO biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

HRS-4642 combined with gemcitabine and nab-paclitaxel in KRAS-G12D mutant advanced pancreatic cancer: A phase Ib/II study (ESMO 2025) - P1/2 | "Conclusions HRS-4642 combined with GA showed encouraging antitumor activity and manageable safety profile in advanced KRAS -G12D mutant PDAC. Follow-up is ongoing for long-term efficacy and safety data."

IO biomarker • Metastases • P1/2 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Live from ESMO | Hengrui Debuts Exhibition Booth with Landmark Data Showcasing Pharma’s Emerging Innovation Power (The Manila Times) - "This year, the company unveiled 46 studies across 14 innovative therapeutic programs, including nine oral presentations, two mini oral sessions, and four late-breaking abstracts (LBAs), underscoring its global R&D strength. These data highlight the company's commitment to multi-cancer coverage and multi-mechanism innovation in oncology."

Clinical data • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer

A Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation (clinicaltrials.gov) - P1/2 | N=47 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Enrolling by invitation ➔ Active, not recruiting | N=70 ➔ 47

Enrollment change • Enrollment closed • Oncology • Solid Tumor • KRAS

HRS-4642 With Nimotuzumab and Chemotherapy for First-line Treatment of Advanced Pancreatic Cancer Patients (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: Zhejiang University | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A Study of HRS-4642 in Combination With Antineoplastic Agents in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=118 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

HRS-4642 in Combination With Gemcitabine and Albumin-bound Paclitaxel and Adebrelimab for Neoadjuvant and Adjuvant Treatment of Pancreatic Cancer (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Ruijin Hospital

New P2 trial • Oncology • Pancreatic Cancer • Solid Tumor

HRS-4642 in Combination With AG for Neoadjuvant and Adjuvant Treatment of Pancreatic Cancer (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Ruijin Hospital | N=60 ➔ 30

Enrollment change • Oncology • Pancreatic Cancer • Solid Tumor

Phase I Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation (clinicaltrials.gov) - P1 | N=102 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Trial completion date: Dec 2024 ➔ Dec 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Solid Tumor • KRAS

HRS-4642 combined with nimotuzumab in the treatment of recurrent or metastatic pancreatic ductal adenocarcinoma: study protocol of a single-arm, prospective phase Ib/II trial. (PubMed, Front Pharmacol) - P1/2 | "This study was registered on ClinicalTrials.gov with NCT06773130. This study protocol has been approved by the Ethics Committee of West China Hospital [2024 (2239)]."

Journal • P1/2 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

HRS-4642 in Combination With AG and Adebrelimab for Neoadjuvant and Adjuvant Treatment of Pancreatic Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Ruijin Hospital | N=20 ➔ 60 | Not yet recruiting ➔ Recruiting

Enrollment change • Enrollment open • Oncology • Pancreatic Cancer • Solid Tumor

Clinical Trial of HRS-4642 Plus SHR-A2102 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=32 | Not yet recruiting | Sponsor: Henan Cancer Hospital

New P1/2 trial • Solid Tumor

An Exploratory Clinical Study of HRS-4642 in Combination With Immunotherapy and Chemotherapy for Pancreatic Cancer (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Shanghai Zhongshan Hospital

New P2 trial • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

A Study of HRS-4642 Monotherapy or in Combination With Adebrelimab in the Treatment of Advanced Biliary Tract Tumors. (clinicaltrials.gov) - P2 | N=49 | Recruiting | Sponsor: Shanghai Zhongshan Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

HRS-4642 combined with Nimotuzumab in the treatment of recurrent or metastatic pancreatic ductal adenocarcinoma with KRAS G12D mutation that has failed systemic therapy (ChiCTR) - P1/2 | N=10 | Recruiting | Sponsor: West China Hospital,Sichuan University; West China Hospital,Sichuan University

New P1/2 trial • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CA 19-9 • KRAS

HRS-4642 Combined with Nimotuzumab in the Treatment of Recurrent or Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: West China Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

New exploration of KRASG12D inhibitors and the mechanisms of resistance. (PubMed, Exp Hematol Oncol) - "developed a high-affinity, selective, long-acting, non-covalent KRASG12D-specific inhibitor and, further combined with the proteasome inhibitor carfilzomib, found that this protocol can achieve the purpose of killing mutant cell lines and inhibiting tumor growth in vitro and in vivo. Here, we aim to describe a potential novel therapy for patients with KRASG12D mutations and present the first KRASG12D-specific inhibitor to be proven as clinically effective. Different mutations of KRAS gene and mechanisms of KRAS drug resistance were also discussed."

Journal • Oncology • Solid Tumor • KRAS

HRS-4642 Combined With Nimotuzumab in the Treatment of Recurrent or Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=10 | Not yet recruiting | Sponsor: West China Hospital

New P1/2 trial • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

HRS-4642 with Nimotuzumab and Chemotherapy for First-line Treatment of Advanced Pancreatic Cancer Patients (clinicaltrials.gov) - P2 | N=32 | Not yet recruiting | Sponsor: Zhejiang University

New P2 trial • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

An exploratory study of HRS-4642 combination therapy for advanced colorectal cancer (ChiCTR) - P1/2 | N=78 | Sponsor: Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

New P1/2 trial • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Hengrui Medicine’s innovative drug SHR-1826 for injection in combination with advanced solid tumors is approved for clinical trials [Google translation] (Jiangsu Hengrui Press Release) - "Recently, Hengrui Medicine's subsidiaries Shanghai Shengdi Pharmaceutical Co., Ltd., Shanghai Hengrui Medicine Co., Ltd. and Suzhou Shengdia Biotechnology Co., Ltd. received the 'Notice of Approval for Drug Clinical Trials' approved and issued by the National Medical Products Administration, approving the company to conduct a multicenter, open Phase IB/II clinical study on the safety, tolerability and efficacy of SHR-1826 for injection, HRS-4642 injection, adebelimumab injection, SHR-9839 for injection, SHR-8068 injection and bevacizumab injection in subjects with advanced solid tumors."

New P1/2 trial • Solid Tumor

HRS-4642 combined with gemcitabine and albumin-bound paclitaxel for neoadjuvant and adjuvant treatment of pancreatic cancer: an xploratory clinical study. (ChiCTR) - P2 | N=20 | Not yet recruiting | Sponsor: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

New P2 trial • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

A Study of HRS-4642 Monotherapy or in Combination with Adebrelimab in the Treatment of Advanced Biliary Tract Tumors. (clinicaltrials.gov) - P2 | N=49 | Not yet recruiting | Sponsor: Shanghai Zhongshan Hospital

New P2 trial • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

HRS-4642 in Combination With AG for Neoadjuvant and Adjuvant Treatment of Pancreatic Cancer (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Ruijin Hospital

Combination therapy • New P2 trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9

Anti-Tumor Efficacy of HRS-4642 and its Potential Combination with Proteasome Inhibition in KRAS G12D-Mutant Cancer (IASLC-WCLC 2024) - "(2) HRS-4642 synergizes with proteasome inhibitor carfilzomib again KRAS G12D-mutant tumors. (3) HRS-4642, or in combination with carfilzomib, has the potential to reshape the tumor immune microenvironment."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • KRAS