M9466 / Jiangsu Hengrui Pharma, EMD Serono - LARVOL DELTA

Phase 1 Study of M9466 Combined With Carboplatin and Platinum-based Anticancer Therapy (DDRiver 521) (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: EMD Serono Research & Development Institute, Inc. | N=54 ➔ 0 | Trial completion date: Oct 2027 ➔ May 2025 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Oct 2027 ➔ May 2025

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Oncology • Solid Tumor

M9466 (HRS-1167): A highly potent and selective PARP1 inhibitor with DNA trapping activity, monotherapy antitumor activity and synergistic potential with DDR inhibitors and chemotherapies (AACR 2025) - P1 | "Currently approved PARP inhibitors (PARPis) such as olaparib, niraparib and talazoparib show synthetic lethality in homologous recombination deficient (HRD) cancers including those with BRCA1/2 mutations...The screen highlighted synergistic activity of M9466 with certain DDR inhibitors (ATR and ATM kinase inhibitors) and with topoisomerase I (Topo I) inhibitors and temozolomide...Here, M9466 enhanced the antitumor efficacy of the ATR inhibitor tuvusertib and the chemotherapy carboplatin. Thus, M9466 has strong single agent synthetic lethal activity in HRD models and combinability with selected DDRis and chemotherapies. Based on these data, Phase I clinical trials are evaluating M9466-based combinations in patients with advanced solid tumors, and colorectal cancer (NCT06421935, NCT06509906)."

Monotherapy • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • HRD • PARP2

Study of HRS-1167 as Monotherapy in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=153 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Ovarian Cancer • Prostate Cancer • Solid Tumor • HRD

M9466 in Combination With Topoisomerase 1 Inhibitors-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511) (clinicaltrials.gov) - P1 | N=54 | Suspended | Sponsor: EMD Serono Research & Development Institute, Inc. | Recruiting ➔ Suspended

Trial suspension • Colorectal Cancer • Oncology • Solid Tumor

Phase 1 Study of M9466 Combined With Carboplatin and Platinum-based Anticancer Therapy (DDRiver 521) (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Initiation date: Jan 2025 ➔ Jul 2025

Trial initiation date • Oncology • Solid Tumor

A Study for the Treatment of Metastatic Prostate Cancer With HRS-1167 Tablets Combined With Abiraterone Acetate Tablets and Prednisone (clinicaltrials.gov) - P1/2 | N=66 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 1 Study of M9466 Combined With Carboplatin and Platinum-based Anticancer Therapy (DDRiver 521) (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: EMD Serono Research & Development Institute, Inc.

Combination therapy • New P1 trial • Oncology • Solid Tumor

Neoadjuvant Treatment of gBRCA-Mutated HER2-Negative Breast Cancer With HRS-1167 and Famitinib ± Camrelizumab (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Fudan University | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2024 ➔ Sep 2024

Enrollment open • IO biomarker • Trial initiation date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • BRCA

A Study for the Treatment of Metastatic Prostate Cancer With HRS-1167 Tablets Combined With Abiraterone Acetate Tablets and Prednisone (clinicaltrials.gov) - P1/2 | N=66 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P1/2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

M9466 in Combination With Topoisomerase 1 Inhibitors-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511) (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of HRS-5041 Tablets Combined With Antitumor Therapy in Subjects With Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Hengrui Medicine: HRS-1167 tablets, HRS-5041 tablets and SHR2554 tablets received drug clinical trial approval notice [Google translation] (Wallstreet.org) - "Hengrui Medicine announced that the company and its subsidiary Chengdu Shengdi Pharmaceutical Co., Ltd. recently received the 'Drug Clinical Trial Approval Notice' for HRS-1167 tablets, HRS-5041 tablets and SHR2554 tablets approved and issued by the National Medical Products Administration, and will conduct clinical trials in the near future. HRS-5041 tablets will be combined with HRS-1167 tablets, SHR2554 tablets, abiraterone acetate tablets (II) and docetaxel for clinical trials of advanced prostate cancer."

New trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of HRS-5041 Tablets Combined With Antitumor Therapy in Subjects With Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=100 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Metastases • New P1/2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

M9466 as Single Agent or in Combination With Tuvusertib in Advanced Solid Tumors (DDRiver 501) (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Oncology • Solid Tumor

Neoadjuvant Treatment of gBRCA-Mutated HER2-Negative Breast Cancer With HRS-1167 and Famitinib ± Camrelizumab (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Fudan University

IO biomarker • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • BRCA

M9466 in Combination With Topoisomerase 1 Inhibitors-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511) (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: EMD Serono Research & Development Institute, Inc.

Combination therapy • Metastases • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Merck’s Innovative Oncology Pipeline of DNA Damage Response Inhibitors and Antibody-Drug Conjugates Poised to Advance Cancer Treatment (Businesswire) - "Merck...shared updates on the company’s oncology pipeline and focused approach to the research and development of potential new medicines designed to improve the futures of people with cancer...This year, the company plans to open multiple new Phase Ib and II clinical studies for tuvusertib and M9466...updates were shared at the company’s Oncology R&D Update Call...A basket trial planned to launch in early 2025 will further explore M9140 monotherapy in tumors with high CEACAM5 expression, with the potential for further exploration in various combinations...M3554 is the next ADC based on the company’s platform, linking an exatecan payload with an anti-GD2 antibody. This potentially first-in-class ADC will enter its first-in-human study later in 2024."

New P1 trial • New P2 trial • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Osteosarcoma • Ovarian Cancer • Prostate Cancer • Sarcoma • Solid Tumor

A phase 1 study of HRS-1167 (M9466), a highly selective PARP1 inhibitor, in patients (pts) with advanced solid tumors. (ASCO 2024) - P1 | "HRS-1167 was well-tolerated and exhibited favorable safety and PK profiles in pts with advanced solid tumors, and demonstrated promising anti-tumor activity in pretreated pts with HRR mutations."

Clinical • Metastases • P1 data • Anemia • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Disorders • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD • PALB2 • PARP2 • RAD51C • RAD51D

M9466 as Single Agent or in Combination With Tuvusertib in Advanced Solid Tumors (DDRiver 501) (clinicaltrials.gov) - P1 | N=70 | Not yet recruiting | Sponsor: EMD Serono Research & Development Institute, Inc.

Combination therapy • Metastases • New P1 trial • Oncology • Solid Tumor

A Phase Ib/II Clinical Study of HRS-1167 in Combination With Bevacizumab in Patients With Recurrent Ovarian Cancer (clinicaltrials.gov) - P1/2 | N=54 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Oncology • Ovarian Cancer • Solid Tumor

A Phase Ib/II Clinical Study of HRS-1167 in Combination With Bevacizumab in Patients With Recurrent Ovarian Cancer (clinicaltrials.gov) - P1/2 | N=54 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Combination therapy • New P1/2 trial • Oncology • Ovarian Cancer • Solid Tumor

Hengrui Medicine’s new PARP inhibitor HRS-1167 (M9466) combination therapy for advanced solid tumors received clinical approval [Google translation] (Jiangsu Hengrui Press Release) - "Recently, Hengrui Medicine and its subsidiaries Suzhou Shengdia Biopharmaceutical Co., Ltd. and Chengdu Shengdi Pharmaceutical Co., Ltd. received the 'Drug Clinical Trial Approval Notice' approved and issued by the National Medical Products Administration, approving the development of a HRS-1167 tablet (Merck code: M9466) Combined with SHR-A1921 for injection or combined with bevacizumab or combined with abiraterone acetate tablets (I) and prednisone/prednisolone (AA-P) for the treatment of advanced entities Phase Ib/II clinical study of tumor....This study will explore the effectiveness and safety of various anti-tumor therapies in treating patients with advanced solid tumors..."

New P1/2 trial • Solid Tumor

Effect of Rifampicin on the Pharmacokinetics of HRS-1167 in Healthy Subjects (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor

Effect of Rifampicin on the Pharmacokinetics of HRS-1167 in Healthy Subjects (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

Effect of Rifampicin on the Pharmacokinetics of HRS-1167 in Healthy Subjects (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P1 trial • Oncology • Solid Tumor