^
    8d
    UPR/ATF4/Noxa pathway overactivation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids. (PubMed, Cell Death Dis)
    Ovarian cancer has a poor clinical prognosis due to chemoresistance following carboplatin/paclitaxel treatment...The therapeutic efficacy of these combinations was also proved in patient-derived tumor organoid models (PDTO), leading to their structural disintegration and reduced viability. Collectively, our study highlights that ABT-737, through BCL-xL inhibition and synergy with ER stress inducers, triggers ovarian cancer death, offering promising strategies for overcoming chemoresistance in relapsed ovarian cancer.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • ATF4 (Activating Transcription Factor 4)
    |
    carboplatin • paclitaxel • nesuparib (JPI-547) • Modeyso (dordaviprone) • ABT-737
    2ms
    To Evaluate the Efficacy and Safety of JPI-547 in Combination With Bevacizumab as Maintenance Therapy in Relapsed Ovarian Cancer (clinicaltrials.gov)
    P2, N=81, Not yet recruiting, Onconic Therapeutics Inc.
    New P2 trial
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HRD • BRCA mutation
    |
    Avastin (bevacizumab) • nesuparib (JPI-547)
    2ms
    To Evaluate the Safety and Tolerability of Study Drug as a Third-line and Beyond Therapy for Recurrent or Metastatic Gastric Cancer (clinicaltrials.gov)
    P1/2, N=49, Not yet recruiting, Onconic Therapeutics Inc.
    New P1/2 trial
    |
    irinotecan • nesuparib (JPI-547)
    4ms
    Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax. (PubMed, Res Sq)
    We report that ONC201 and highly potent second generation ClpP agonists (TR-57, TR-107), promote induction of senescence in triple-negative breast cancer (TNBC) cell lines...By contrast, cells treated with the cell cycle inhibitor and senescence inducer, abemaciclib rapidly regained p-Rb and Myc expression and cell proliferation following washout...Combining a ClpP agonist with a PARP inhibitor (olaparib) produced an additive effect. In summary, we show that ClpP activators stably induce an irreversible senescence in a ClpP-dependent manner that synergizes with venetoclax in TNBC cells.
    Journal • PARP Biomarker • IO biomarker
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CHEK2 (Checkpoint kinase 2) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    Venclexta (venetoclax) • Lynparza (olaparib) • Verzenio (abemaciclib) • nesuparib (JPI-547) • Modeyso (dordaviprone)
    7ms
    JPI-547, a Dual Inhibitor of PARP/Tankyrase, Shows Antitumor Activity Against Pancreatic Cancers with Homologous Recombination Repair Deficiency or Wnt-Addiction. (PubMed, Int J Biol Sci)
    JPI-547 outperformed most PARP inhibitors, with a half-maximal inhibitory concentration approximately 10-fold lower than that of olaparib. PDAC cells reliant on Wnt signaling due to pathogenic RNF43 mutations showed increased susceptibility to JPI-547 without altering homologous recombination repair efficiency. JPI-547 disrupts the Wnt/β-catenin pathway in RNF43-mutated cells and inhibits the oncogenic YAP pathway, highlighting its multifaceted therapeutic potential in PDAC with HRD or Wnt-addiction.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RNF43 (Ring Finger Protein 43)
    |
    HRD
    |
    Lynparza (olaparib) • nesuparib (JPI-547)
    9ms
    The therapeutic potential of repurposed mebendazole, alone and in synergistic combination with ONC201, in the treatment of diffuse midline glioma. (PubMed, Am J Cancer Res)
    Finally, one pair of ONC201-sensitive and ONC201-resistant DMG cell lines with acquired resistance showed same responsiveness to MBZ with similar values of IC50 and Emax. In conclusion, MBZ demonstrates high growth-inhibitory/proapoptotic activity, chemosensitization property to ONC201 and the ability to overcome ONC201 resistance in DMG cell cultures, proposing as a new low-toxicity therapeutic for DMG, with a potential to be used in second-line treatment and/or in combination protocols.
    Journal • PARP Biomarker
    |
    CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • ANXA5 (Annexin A5)
    |
    nesuparib (JPI-547) • Modeyso (dordaviprone) • mebendazole
    1year
    PENELOPE: First-line Carboplatin and Paclitaxel in Combination With Pembrolizumab, Followed by Maintenance Pembrolizumab With or Without Nesuparib, in Patients With Newly Diagnosed Advanced or Recurrent MMR-proficient (pMMR) Endometrial Cancer (clinicaltrials.gov)
    P2, N=92, Recruiting, Yonsei University | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Keytruda (pembrolizumab) • carboplatin • paclitaxel • nesuparib (JPI-547)
    1year
    Study to Assess the Safety, Tolerability of JPI-547 in Combination With Modified FOLFIRINOX or Gemcitabine-nab-paclitaxel in Patients With Locally Advanced and Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P1, N=30, Recruiting, Onconic Therapeutics Inc. | Trial completion date: Sep 2026 --> Jun 2026
    Trial completion date
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • nesuparib (JPI-547)
    1year
    Study to Assess the Safety, Tolerability of JPI-547 in Combination With Modified FOLFIRINOX or Gemcitabine-nab-paclitaxel in Patients With Locally Advanced and Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P1, N=30, Recruiting, Onconic Therapeutics Inc. | Trial completion date: Dec 2024 --> Sep 2026 | Trial primary completion date: Dec 2024 --> Mar 2026
    Trial completion date • Trial primary completion date
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • nesuparib (JPI-547)
    over1year
    Study to Assess the Safety, Tolerability of JPI-547 in Combination With Modified FOLFIRINOX or Gemcitabine-nab-paclitaxel in Patients With Locally Advanced and Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P1, N=24, Recruiting, Onconic Therapeutics Inc. | Not yet recruiting --> Recruiting | Trial completion date: Aug 2023 --> Dec 2024 | Trial primary completion date: Aug 2023 --> Dec 2024
    Enrollment open • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • nesuparib (JPI-547)
    over1year
    A Study to Evaluate the Efficacy and Safety of JPI-547 in Platinum-resistant, Advanced/Relapsed Ovarian Cancer Subjects Previously Treated With a PARP Inhibitor (clinicaltrials.gov)
    P2, N=58, Active, not recruiting, Onconic Therapeutics Inc. | Not yet recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    nesuparib (JPI-547)
    over1year
    PENELOPE: First-line Carboplatin and Paclitaxel in Combination With Pembrolizumab, Followed by Maintenance Pembrolizumab With or Without Nesuparib, in Patients With Newly Diagnosed Advanced or Recurrent MMR-proficient (pMMR) Endometrial Cancer (clinicaltrials.gov)
    P2, N=92, Not yet recruiting, Yonsei University
    New P2 trial
    |
    Keytruda (pembrolizumab) • carboplatin • paclitaxel • nesuparib (JPI-547)