Paxonin (senaparib) / IMPACT Therap, Huadong Medicine - LARVOL DELTA

Discovery and development of a potent and highly selective ATR inhibitor IMP9064 (AACR 2025) - P1/2 | "IMP9064 has entered a phase 1/2 study to evaluate the safety and efficacy either as monotherapy or in combination with PARP inhibitor Senaparib in patients with advanced solid tumors (ClinicalTrials.gov Identifier: NCT05269316). The recommended phase 2 dose (RP2D) has been determined and IMP9064 is currently in expansion studies for selected tumors."

Colorectal Cancer • Oncology • Solid Tumor • PKMYT1

Study to Evaluate IMP9064 as a Monotherapy or in Combination in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=61 | Recruiting | Sponsor: Impact Therapeutics, Inc. | Phase classification: P1 ➔ P1/2 | Trial completion date: Jul 2025 ➔ Dec 2026 | Trial primary completion date: Jul 2025 ➔ Dec 2026

Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Multifunctional nanoparticle-mediated targeting of metabolic reprogramming and DNA damage response pathways to treat drug-resistant triple-negative breast cancer. (PubMed, J Control Release) - "Herein, a P-gp-inhibiting and GSH-responsive multifunctional drug carrier targeting integrin αvβ3 was synthesised for the delivery of Lonidamine-prodrug (M1, glycolysis inhibitor) and Senaparib (Se, Poly [ADP-ribose] polymerase inhibitor). Experimental results show that iPR@M1/Se nanoparticles effectively promote dendritic cell maturation and T lymphocyte activation, which elicits long-term immune memory responses, and prevents tumour recurrence and lung metastasis. Therefore, these multifunctional nanoparticles have great potential and provide a clinically relevant and valuable option for Olaparib-resistant TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CGAS • HRD • STING

Duplexed CeTEAM drug biosensors reveal determinants of PARP inhibitor selectivity in cells. (PubMed, J Biol Chem) - "Our results reveal that most PARPi are equipotent for both PARPs, including the next-generation drug, senaparib. However, benzimidazole carboxamide (niraparib) derivatives demonstrated PARP1-selective tendencies, while pthalazinones (olaparib) favored PARP2. AZD5305, a reported PARP1-selective inhibitor with characteristics of both series, was the exception and appears ∼1600-fold more potent towards PARP1. In agreement with current understanding, we see that trapping-associated S/G2-phase transitions positively correlate with PARP1/2 binding potency, while some potent binders, such as veliparib, did not - likely reflecting their allosteric influence on DNA retention...The PARP1/2 CeTEAM platform thus provides a structural roadmap for the development of selective PARPi and should facilitate the discovery of targeted therapies. Furthermore, our results highlight that multiplexing CeTEAM biosensors and layered genetic perturbations can systematically profile determinants of..."

Journal • Oncology • PARP2

Study of Senaparib in Combination With Temozolomide in ARID1A Mutation Associated Ovarian Cancer (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting ➔ Recruiting

Enrollment open • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor

Senaparib Approved by NMPA for 1L Maintenance Therapy in Ovarian Cancer (PRNewswire) - "IMPACT Therapeutics...is pleased to announce that Senaparib Capsules has received marketing authorization in China from National Medical Products Administration (NMPA) as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy....The approval is based on FLAMES Study....The results of FLAMES Study showed that Senaparib demonstrated significant improvement in median PFS compared to placebo (PFS not reached vs 13.6 months, HR 0.43, P < 0.0001), irrespective of BRCA status."

China approval • Fallopian Tube Cancer • Ovarian Cancer • Peritoneal Cancer

Results from the first-in-human study of ATR inhibitor, IMP9064 monotherapy dose escalation in patients with advanced solid tumors (ESMO 2024) - P1 | "Here reports the results of Part 1 from the phase 1/2 study. The study consists of 4 parts: dose-escalation and dose-expansion of IMP9064 monotherapy and combination with senaparib (PARPi). IMP9064 has demonstrated a favorable safety profile and preliminary clinical efficacy signal and sustained clinical benefit in late-stage AST, which warrants further development of IMP9064. After RP2D is determined in May, enrollment in an expansion cohort will proceed."

Clinical • Metastases • Monotherapy • P1 data • Biliary Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastrointestinal Cancer • Leiomyosarcoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Uterine Corpus Leiomyosarcoma

Study of Senaparib in Combination With Temozolomide (clinicaltrials.gov) - P2 | N=18 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

New P2 trial • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor

IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=59 | Completed | Sponsor: Impact Therapeutics, Inc. | Recruiting ➔ Completed | N=113 ➔ 59 | Trial completion date: Dec 2025 ➔ Apr 2024 | Trial primary completion date: Oct 2024 ➔ Apr 2024

Combination therapy • Enrollment change • Metastases • Trial completion • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

A Clinical Study of IMP4297 Capsule (JS109) Combined With Irinotecan in the Treatment of Advanced Malignant Solid Tumors (clinicaltrials.gov) - P1/2 | N=4 | Terminated | Sponsor: Shanghai Jun Pai Ying Shi Therapeutics Co., Ltd. | N=57 ➔ 4 | Trial completion date: Jul 2024 ➔ Sep 2023 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2024 ➔ Sep 2023; The sponsor voluntarily requested termination

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Study to Evaluate IMP9064 as a Monotherapy or in Combination in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=61 | Recruiting | Sponsor: Impact Therapeutics, Inc. | Phase classification: P1/2 ➔ P1

Combination therapy • Metastases • Monotherapy • Phase classification • Oncology • Solid Tumor

The discovery of a potent PARP1 inhibitor Senaparib. (PubMed, Mol Cancer Ther) - "In combination studies, Senaparib used with temozolomide (TMZ) had shown strong synergistic cytotoxicity in both in vitro and in vivo experiments. Senaparib represents a novel class of PARP1 inhibitors that can be used for the treatment of cancer. A phase III clinical study of Senaparib for maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer has met its primary endpoint, and a new drug application of Senaparib has been accepted by National Medical Products Administration (NMPA) of China for review."

Journal • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD • PARP2

Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial. (PubMed, Nat Med) - P3 | "These results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 ."

Journal • Metastases • P3 data • Gynecology • Obstetrics • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2

Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial (Nat Med, Nature) - P3 | N=393 | FLAMES (NCT04169997) | Sponsor: Impact Therapeutics, Inc. | "At the prespecified interim analysis, the median progression-free survival was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32–0.58; P < 0.0001). The benefit with senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively."

P3 data • Ovarian Cancer

Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial (Nat Med, Nature) - P3 | N=393 | FLAMES (NCT04169997) | Sponsor: Impact Therapeutics, Inc. | "At the prespecified interim analysis, the median progression-free survival was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32–0.58; P < 0.0001). The benefit with senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively."

P3 data • Ovarian Cancer

Senaparib Maintenance In Newly Diagnosed Advanced Ovarian Cancer: FLAMES Study (ESGO 2024) - "Conclusion First-line maintenance Senaparib significantly reduced the risk of progression or death in advanced OC patients, irrespective of BRCA mutation status. Senaparib demonstrated favorable safety profiles, no additional safety signals were identified."

Clinical • Metastases • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Huadong Pharmaceutical (000963.SZ) subsidiary will obtain exclusive marketing rights for Senapalib from Yingpai Pharmaceuticals in mainland China [Google translation] (Investing.com) - "According to Zhitong Finance APP, Huadong Pharmaceutical...announced that on December 19, 2023, the company’s wholly-owned subsidiary Hangzhou Sino-US Huadong Pharmaceutical Co., Ltd. (referred to as 'Sino-US Huadong') and Nanjing Yingpai Pharmaceutical Co., Ltd. Shanghai Junpai Yingshi Pharmaceutical Co., Ltd. (referred to as 'Yingpai Pharmaceutical'), a wholly-owned subsidiary, signed an exclusive marketing service agreement. Sino-American Huadong has obtained the exclusive license for Senaparib (IMP4297, Senaparib) (referred to as the 'licensed product' or 'subject product', the Chinese name shall be subject to the final approval document) from Yingpai Pharmaceuticals in mainland China (referred to as the 'licensed area') Marketing rights."

Licensing / partnership • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

FLAMES: RANDOMIZED PHASE 3 TRIAL OF MAINTENANCE SENAPARIB IN PATIENTS WITH NEWLY DIAGNOSED ADVANCED OVARIAN CANCER (IGCS 2023) - "No new safety signals were identified among all subgroups. Conclusion/Implications Maintenance senaparib significantly improved PFS regardless of FIGO stage, 1L treatment response, surgical timing and residual disease status versus placebo in patients with newly diagnosed advanced OC."

Clinical • Late-breaking abstract • Metastases • P3 data • Oncology • Ovarian Cancer • Solid Tumor • BRCA

SABRINA study: A phase II study of senaparib monotherapy for patients (pts) with BRCA1/2 mutated recurrent platinum-sensitive ovarian cancer (PSOC) (ESMO 2023) - P2 | "Conclusions Senaparib demonstrated clinically meaningful antitumor activity and manageable safety profile in BRCA1/2 mutated recurrent PSOC. The OS was immature but seemed to be improved."

Clinical • Monotherapy • P2 data • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2

First-in-human study of ATR inhibitor IMP9064 monotherapy and in combination with PARP inhibitor senaparib in patients with advanced solid tumors (ESMO 2023) - P1/2 | "Conclusions These results indicate that IMP9064 monotherapy appears to be well-tolerated and support further dose escalation. More MRD and biomarker analyses are underway."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Efficacy and safety of senaparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer (FLAMES study): A randomized, double-blind, placebo-controlled, phase III trial (ESMO 2023) - P3 | "Table: LBA36 Senaparib (n=271), m Placebo (n=133), m HR (95%CI), P value PFS (BICR) NR 13.6 0.43 (0.32-0.58) P < 0.0001 PFS (BICR) BRCA + NR 15.6 0.43 (0.24-0.76) P = 0.0026 PFS (BICR) BRCA- NR 12.9 0.43 (0.30-0.61) P < 0.0001 PFS (INVR) NR 11.1 0.43 (0.32-0.57) P < 0.0001 PFS (INVR) BRCA + NR 11.1 0.33 (0.20-0.56) P < 0.0001 PFS (INVR) BRCA- NR 11.1 0.48 (0.34-0.67) P < 0.0001 TFST NR 14.4 0.44 (0.33-0.59) P < 0.0001 BICR, blinded independent central review; INVR, investigator review; HR, hazard ratio; NR, not reached; PFS, progression-free survival; BRCA +, breast cancer susceptibility gene (BRCA) mutation positive; BRCA -, BRCA mutation negative; TFST, time to first subsequent therapy or death; m, month Conclusions 1L maintenance Senaparib led to an unprecedented reduction in the risk of progression or death versus placebo in OC, regardless of biomarker status. Senaparib was well tolerated, no new safety signals were identified."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

SENAPARIB, A PARP INHIBITOR, IN PATIENTS WITH BRCA1/2 MUTATED PLATINUM SENSITIVE RECURRENT OVARIAN CANCER: SUBGROUP ANALYSIS FROM SABRINA STUDY. (IGCS 2023) - P2 | "As of 30 Jan 2023, 93 pts were enrolled. 59%/41% pts were partially/fully platinum sensitive. Median lines of prior systemic chemotherapy(CT) was 2 (range 2-7), and 71%/29% received 2 / ≥ 3 lines of CT."

Clinical • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2

Senaparib Significantly Improves PFS Vs Placebo in Advanced Ovarian Cancer (Cancer Network) - P3 | N=393 | FLAMES (NCT04169997) | Sponsor: Impact Therapeutics, Inc. | "Senaparib (IMP4297) maintenance monotherapy led to a reduction in the risk of progression or death compared with placebo in patients with newly diagnosed advanced ovarian cancer regardless of BRCA mutation status, according to results from the phase 3 FLAMES trial (NCT04169997) presented at the 2023 European Society of Medical Oncology (ESMO) Congress. The median progression-free survival (PFS) by blinded independent central review (BICR) via RECIST 1.1 criteria was not reached (NR) in the senaparib arm compared with 13.6 months in the placebo arm, yielding a 57% risk reduction in progression or death with senaparib (HR, 0.43; 95% CI, 0.32-0.58; P <.0001). At 12 months, the PFS rate in the senaparib arm was 72.2% vs 53.7%, and at 24 months it was 63.0% vs 31.3%."

P3 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=113 | Recruiting | Sponsor: Impact Therapeutics, Inc. | Phase classification: P1 ➔ P1/2 | Trial completion date: Jan 2023 ➔ Dec 2025 | Trial primary completion date: Oct 2022 ➔ Oct 2024

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

Efficacy And Safety Of Senaparib As Maintenance Treatment In Patients With Newly Diagnosed Advanced Ovarian Cancer (FLAMES Study): A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial (ESGO 2023) - "The most common grade â¥3 TEAEs were anemia (x%) , thrombocytopenia (x%), and neutropenia (x%).Conclusion Pts who received Sena had a meaningful and significant improvement in PFS compared to those who received PBO and the PFS is much longer than other PARP inhibitors, regardless of biomarker status. Sena was well tolerated, no new safety signals were identified."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Endometrial Cancer • Gynecologic Cancers • Hormone Receptor Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA