Partruvix (pamiparib) / EMD Serono, BeiGene - LARVOL DELTA

SPRING: Study of Precision Treatment for Rare Tumours in China Guided by PDO and NGS (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Peking University Shenzhen Hospital

Biomarker • New P2 trial • Oncology

Mechanistic Modeling of Spatial Heterogeneity of Drug Penetration and Exposure in the Human Central Nervous System and Brain Tumors. (PubMed, Clin Pharmacol Ther) - "The model was validated by comparisons of model predictions and clinically observed data of six drugs (abemaciclib, ribociclib, pamiparib, olaparib, temuterkib, and ceritinib) in glioblastoma patients. The 9-CNS model is a first-of-its kind, mechanism-based computational modeling platform that enables early reliable prediction of spatial CNS and tumor pharmacokinetics based on plasma concentration-time profiles. It provides a valuable tool to assist rational drug development and treatment for brain cancer."

Heterogeneity • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

BGB-290-103: Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=139 | Completed | Sponsor: BeiGene | Phase classification: P1b ➔ P1

Metastases • Phase classification • Breast Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • AR • BRCA • HRD

A phase II single-arm, open-label trial of pamiparib in metastatic castration-resistant prostate cancer (mCRPC) patients with deleterious germline or somatic BRCA1/2 alterations or homologous recombination deficiency (HRD): Interim analysis of efficacy and safety results (ESMO Asia 2024) - P2 | "ORR and PSA response rate was 20% and 100%, respectively. Conclusions The results suggest that pamiparib demonstrates significant antitumor activity as a monotherapy for mCRPC pts with deleterious germline or somatic BRCA1/2 alterations or HRD score 43."

Clinical • Metastases • P2 data • Breast Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD

Biomarker-driven targeted therapy in platinum-resistant ovarian cancer (BRIGHT): An open-label, multicenter, umbrella trial (ESMO 2024) - P2 | "The BRIGHT trial (NCT05044871) aimed to evaluate the efficacy and safety of biomarker-driven targeted combinatorial therapies of pamiparib (Pami, a PARP inhibitor), tislelizumab (TIS, a PD-1 inhibitor), bevacizumab (BEV), and nab-paclitaxel (nab-PTX) in pts with PROC. These findings highlight the potential clinical benefits of biomarker-driven targeted therapies in pts with PROC. The majority of pts in this study had BRCAwt tumors with positive CD8+ TILs (≥3), and PD-1 inhibitor-based combinatorial regimen (TIS + BEV + nab-PTX) resulted in notable ORR and PFS in this patient population."

Biomarker • Clinical • IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • BRCA • CD8

Phase I study of pamiparib and cabozantinib in patients with metastatic solid tumors harboring homologous recombination deficiency (HRD) (ESMO 2024) - P1 | "Preliminary evidence in this study showed that the treatment with oral pamiparib 60 mg BID and cabozantinib 40 mg QD was well-tolerated and has yielded modest antitumor activity in heavily pretreated patients with metastatic HRD malignancies."

Clinical • Metastases • P1 data • Oncology • Sarcoma • Solid Tumor • ARID1A • BRCA1 • BRCA2 • HRD • KDR • MET • PALB2 • RAD50

Efficacy and safety of pamiparib monotherapy in recurrent ovarian cancer (rOC) after prior PARPi exposure: A prospective, open label, single-arm, phase II study (ESMO 2024) - P2 | "Pamiparib monotherapy showed limited clinical efficacy in rOC pts who had used PARPi before. In PARPi after PARPi treatment strategy, PARPi monotherapy should be selected prudently."

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

Study of Pamiparib in Newly Diagnosed and rGBM (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Nader Sanai | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

PNOC017: BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas (clinicaltrials.gov) - P1 | N=78 | Recruiting | Sponsor: University of California, San Francisco | Trial primary completion date: Jun 2024 ➔ Jun 2026

Combination therapy • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • IDH1 • IDH2

Co-Targeting of DTYMK and PARP1 as a Potential Therapeutic Approach in Uveal Melanoma. (PubMed, Cells) - "In vitro tests on MP41 (BAP1 positive) and MP46 (BAP1 negative) cancer cell lines using inhibitors pamiparib (PARP1) and Ymu1 (DTYMK) demonstrated significant cytotoxic effects...Our hypothesis of the double hit into tumoral DNA metabolism as a possible therapeutic option in uveal melanoma was confirmed since combined targeting of DTYMK and PARP1 affected all tested cytophysiological parameters with the highest efficiency. Our in vitro findings provide insights into novel therapeutic avenues for managing uveal melanoma, warranting further exploration in preclinical and clinical settings."

Journal • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1 • PARP1

Pamiparib Combined With Surufatinib for the Neoadjuvant Treatment of Unresectable Ovarian Cancer (clinicaltrials.gov) - P2 | N=37 | Active, not recruiting | Sponsor: Bai-Rong Xia | N=20 ➔ 37

Enrollment change • Metastases • Oncology • Ovarian Cancer • Solid Tumor • HRD

BRCAness, DNA gaps, and gain and loss of PARP inhibitor–induced synthetic lethality (J Clin Invest) - "Recent studies have revealed that changes of specific functional defects of BRCA1/2-deficient cells, particularly their defects in suppressing and protecting single-stranded DNA gaps, contribute to the gain or loss of PARPi-induced synthetic lethality. These findings not only shed light on the mechanism of action of PARPis, but also lead to revised models that explain how PARPis selectively kill BRCA-deficient cancer cells. Furthermore, new mechanistic principles of PARPi sensitivity and resistance have emerged from these studies, generating potentially useful guidelines for predicting the PARPi response and design therapies for overcoming PARPi resistance."

Review • Breast Cancer

Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • ARID1A • BRCA1 • BRCA2 • CHEK1 • CHEK2 • EMSY • PARP1 • PTEN • RAD50

Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 16 substudy 37: Pamiparib (ANZCTR) - P2 | N=16 | Terminated | Sponsor: The University of Sydney | Recruiting ➔ Terminated

Trial termination • Hematological Disorders • Hematological Malignancies • Oncology • BRCA • BRCA1 • BRCA2 • ERCC4

Individualized radiotherapy plus PARP inhibitors in locally advanced esophageal cancer (ChiCTR) - P2 | N=55 | Not yet recruiting | Sponsor: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine Affiliated Sh

New P2 trial • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology

ATM, BLM, and CDH1 gene co-mutations in a high-grade endometrial stromal sarcoma patient with multiple abdominal cavity metastases: a case report and literature review. (PubMed, BMC Geriatr) - "Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS."

IO biomarker • Journal • Review • Stroma • Oncology • Pain • Sarcoma • Solid Tumor • Uterine Cancer • CDH1

Phase 1b study to assess the safety, tolerability, and clinical activity of pamiparib in combination with temozolomide in patients with locally advanced or metastatic solid tumors. (PubMed, Cancer Med) - P1b | "Pamiparib in combination with TMZ had a manageable safety profile. Further investigation of the efficacy of this combination in tumor types with specific DNA damage repair deficiencies is warranted."

Combination therapy • Journal • Metastases • P1 data • Breast Cancer • Fatigue • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • HRD • PARP1

Pamiparib, A Novel Intervention with Anti-neoplastic Activity for the Treatment of Glioblastoma. (PubMed, Am J Med Sci) - No abstract available

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

BGB-290-AU-002: Phase 1a/1b BGB-290 for Advanced Solid Tumors. (clinicaltrials.gov) - P1 | N=101 | Completed | Sponsor: BeiGene | Phase classification: P1a/1b ➔ P1

Metastases • Phase classification • Breast Cancer • Gastric Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2

BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov) - P3 | N=300 | Enrolling by invitation | Sponsor: BeiGene | Trial completion date: Aug 2024 ➔ Dec 2026 | Trial primary completion date: Aug 2024 ➔ Dec 2026

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

PET imaging of PARP-1 expression using a novel 18F-labeled Olaparib (SNMMI 2024) - "08 μM, Pamiparib: IC50 = 52. Photolabeling enables the efficient preparation of PARP-1 targeted radioactive ligands under mild conditions. 18F-PARPi-OMe can be used to noninvasively visualize PARP expression with good tumor-to-background ratios. Further PET/CT imaging in other tumor models and biodistribution studies will be conducted."

Oncology • HRD • PARP1

Neoadjuvant pamiparib in patients with newly diagnosed advanced ovarian cancer: A single-arm, prospective phase II trial. (ASCO 2024) - "The treatment consists of paclitaxel 175mg/m2 on Day 1 and carboplatin AUC 5 on Day 2, every 3 weeks, for a maximum of 6 cycles. The combination of pamiparib with neoadjuvant chemotherapy and bevacizumab showed promising efficacy and acceptable toxicity in patients with newly diagnosed advanced ovarian cancer. We will report more data in the future. Clinical trial information: ChiCTR2200059119."

Clinical • Metastases • P2 data • Anemia • Endometrial Cancer • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Thrombocytopenia

PET imaging of PARP-1 expression using a novel 18F-labeled Olaparib (SNMMI 2024) - "08 μM, Pamiparib: IC50 = 52. Photolabeling enables the efficient preparation of PARP-1 targeted radioactive ligands under mild conditions. 18F-PARPi-OMe can be used to noninvasively visualize PARP expression with good tumor-to-background ratios. Further PET/CT imaging in other tumor models and biodistribution studies will be conducted."

Oncology • HRD • PARP1

PET imaging of PARP-1 expression using a novel 18F-labeled Olaparib (SNMMI 2024) - "08 μM, Pamiparib: IC50 = 52. Photolabeling enables the efficient preparation of PARP-1 targeted radioactive ligands under mild conditions. 18F-PARPi-OMe can be used to noninvasively visualize PARP expression with good tumor-to-background ratios. Further PET/CT imaging in other tumor models and biodistribution studies will be conducted."

Oncology • HRD • PARP1

PET imaging of PARP-1 expression using a novel 18F-labeled Olaparib (SNMMI 2024) - "08 μM, Pamiparib: IC50 = 52. Photolabeling enables the efficient preparation of PARP-1 targeted radioactive ligands under mild conditions. 18F-PARPi-OMe can be used to noninvasively visualize PARP expression with good tumor-to-background ratios. Further PET/CT imaging in other tumor models and biodistribution studies will be conducted."

Oncology • HRD • PARP1