HRS-4642 / Jiangsu Hengrui Pharma - LARVOL DELTA

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

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

Unveiling mechanisms of MRTX1133 resistance in PDAC models (AACR 2026) - "To investigate these mechanisms, we established resistant cell lines through stepwise escalation of MRTX1133, the first covalent inhibitor of KRAS G12D to enter clinical evaluation, in KRAS G12D-mutant modelsThese resistant cells maintain stable phenotypes to MRTX-1133 both in vitro and in vivo, and exhibited broad cross-resistance to other KRAS G12D inhibitors, such as RMC9805 and HRS-4642, with partial resistance observed toward the pan-RAS inhibitor RMC6236.Bioinformatic analysis of both resistant models revealed a spectrum of convergent adaptive mechanisms, including: (1) altered oncogenic signaling networks, (2) upregulation of cell cycle and drug efflux regulators, and (3) epithelial-mesenchymal transition (EMT). The established resistant models serve as physiologically relevant platforms for biomarker discovery and the development of rational combination therapies. Using these models, functional studies demonstrated that targeting core vulnerabilities—including..."

Oncology • KRAS

A Phase III Study of HRS-4642 Combined With AG (Nab-paclitaxel and Gemcitabine) as Conversion Therapy for Locally Advanced Pancreatic Cancer (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: The First Affiliated Hospital with Nanjing Medical University

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

HRS-4642 in Combination With Nimotuzumab and Chemotherapy for BRPC With KRAS G12D Mutation (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Zhejiang University | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2025 ➔ Feb 2026

Enrollment open • Trial initiation date • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

HRS-4642-206: Phase IB/II clinical study of the safety, tolerability and efficacy of HRS-4642 in combination with other anti-tumor drugs in subjects with solid tumors (ChiCTR) - P1/2 | N=60 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital; Peking Union Medical College Hospital

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

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=20 | Recruiting | Sponsor: West China Hospital,Sichuan University; West China Hospital,Sichuan University | N=10 ➔ 20

Enrollment change • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CA 19-9 • KRAS

A first-in-human phase I study of a novel KRAS G12D inhibitor HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation (ESMO 2023) - P1 | "Conclusions HRS-4642 showed a tolerable safety profile and preliminary anti-tumor activity in advanced solid tumors harboring KRAS G12D mutation. Dose escalation is ongoing and expected to proceed to dose expansion soon."

Clinical • Late-breaking abstract • Metastases • P1 data • Appendix Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • KRAS

HRS-4642 Combination With Other Antitumor Therapies in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Exploratory Platform Research on Precision Therapy of Advanced Pancreatic Cancer (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Fudan University | Not yet recruiting ➔ Recruiting | N=120 ➔ 160

Enrollment change • Enrollment open • Oncology • Pancreatic Cancer • 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 | Recruiting | Sponsor: Ruijin Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Solid Tumor

HRS-4642 Combination With Other Antitumor Therapies in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=60 | Not yet recruiting | Sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.

New P1/2 trial • Oncology • Pancreatic Cancer • Solid Tumor

HRS-4642 Combined With Nimotuzumab in the Treatment of Recurrent or Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: West China Hospital | N=10 ➔ 20

Enrollment change • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

HRS 4642 Injection Combined With AG Versus Placebo Combined With AG Therapy in First-Line Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P3 | N=588 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P3 trial • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

HRS-4642 in Combination With Nimotuzumab and Chemotherapy for BRPC With KRAS G12D Mutation (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Zhejiang University

New P2 trial • Oncology • Pancreatic Cancer • 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