veliparib (ABT-888) / AbbVie - LARVOL DELTA

Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma: A Randomized Clinical Trial. (PubMed, JAMA Oncol) - P2/3 | "This trial found that adding veliparib to adjuvant temozolomide did not significantly extend OS in patients with newly diagnosed, MGMT-hypermethylated glioblastoma. ClinicalTrials.gov Identifier: NCT02152982."

Clinical • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Hematological Disorders • Oncology • Solid Tumor • MGMT

Randomized phase II/III trial of veliparib or placebo in combination with adjuvant temozolomide in newly diagnosed glioblastoma (GBM) patients with MGMT promoter hypermethylation (Alliance A071102). (ASCO 2022) - P2/3 | "Veliparib combined with adjuvant TMZ therapy was not associated with significant extension in OS or PFS in newly diagnosed, MGMT hypermethylated GBM pts. However, a subset of pts treated with TMZ+veliparib may have an extended survival following re-treatment with TMZ at first recurrence."

Clinical • Combination therapy • P2/3 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

Long-term results from NRG-GI002: A phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC). (ASCO-GI 2023) - P2 | "Primary endpoint (EP) and available secondary EPs (from EA1 using veliparib [V], PARPi; and EA2 using pembrolizumab [P], anti-PD-1) have been previously reported... Stage II/III pts with MSS LARC (with any ONE of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to CA (neoadjuvant FOLFOX [x 4mo] → chemoRT [capecitabine with 50.4Gy] → surgery 8-12 wks later)... With longer follow-up, addition of V to TNT provided no significant differences in the NAR score or 3yr outcomes. The addition of P to TNT was associated with a statistically significant improvement in 3yr OS, but not DFS. Correlative molecular analyses are ongoing."

Clinical • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

Safety and Tolerability of Berzosertib, an Ataxia-Telangiectasia-Related Inhibitor, and Veliparib, an Oral Poly (ADP-ribose) Polymerase Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors. (PubMed, JCO Precis Oncol) - "This combination shows antitumor activity, including in patients with and without homologous recombination-compromised tumors and those previously treated with platinum. Adding berzosertib further increases the DDR response elicited by combination cisplatin/veliparib treatment in BRCA-wildtype patients, indicating increased replication stress at the RP2D/MTD."

Journal • Ataxia • Hematological Disorders • Immunology • Leukopenia • Movement Disorders • Neutropenia • Oncology • Primary Immunodeficiency • Solid Tumor • Thrombocytopenia • BRCA • RAD51

SWOG S1929: Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer (ES-SCLC). (ASCO 2023) - P2 | "In a retrospective analysis of a study with veliparib (PARP inhibitor [PARPi]) and temozolomide in patients with SCLC, Schlafen-11 (SLFN11) predicted PFS and OS benefit for the addition of PARPi. This study met its primary endpoint demonstrating that maintenance AT improved PFS in SLFN11-selected patients with ES-SCLC. Hematologic toxicity was increased with AT as expected, with majority being grade 3 anemia. This study demonstrates the feasibility of conducting biomarker selected trials in SCLC, paving the way for future evaluation of novel therapies in selected SCLC populations."

Clinical • IO biomarker • P2 data • Anemia • Febrile Neutropenia • Immune Modulation • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • SLFN11

Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial. (PubMed, Eur J Cancer) - "Final OS data indicate that the PFS improvement shown in the primary analysis did not translate into an OS benefit. The long survival times observed in both arms suggest that combination therapy with paclitaxel and carboplatin provides clinical benefit in the population of patients with BRCA1/2-mutated metastatic breast cancer."

Journal • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2 • HER-2

Prognostic value of CT radiomics in patients with gBRCA1/2 and PALB2 and advanced pancreas cancer (AACR 2026) - "Introduction: A phase II trial at Memorial Sloan Kettering Cancer Center (MSK), IRB #12-045 evaluated cisplatin/gemcitabine +/- PARP inhibitor veliparib in patients with gBRCA1/2 and PALB2 (core homologous repair deficiency; cHRD) and advanced pancreas cancer (PDAC). CT radiomic features demonstrate prognostic value for overall survival in patients with cHRD and advanced PDAC, supporting radiomics as a promising tool for patient stratification in future trials. Ongoing work is evaluating correlations between radiomic signatures and genomic profiles to further refine predictive models."

Clinical • Metastases • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRCA1 • BRCA2 • PALB2

A Randomised Phase II study of Veliparib, Radiotherapy and Temozolomide in patients with unmethylated O (6)-methylguanine-DNA methyltransferase (MGMT) Glioblastoma (brain cancer) (VERTU study) (ANZCTR) - P2 | N=120 | Completed | Sponsor: The University of Sydney | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

FIRST-LINE POLY(ADENOSINE DIPHOSPHATE -RIBOSE) POLYMERASE INHIBITOR MAINTENANCE IN OVARIAN CANCER: A SYSTEMATIC REVIEW AND META -ANALYSIS (IGCS 2026) - "Severe adverse events increased substantially (RR 2.40, 95%CI 1.16 -4.93), with regimen-dependen t haematologic toxicity, whereas high -grade toxicity ranged from veliparib RR 1.15 to niraparib RR 4.73. Seven randomized trials reported in 13 publications, encompassing 4013 patients, were included: SOLO -1, PRIMA, PAOLA -1, VELIA, ATHENA -MONO, PRIME and FLAMES. PARP maintenance significantly improved progression -free survival overall (HR 0.57, 95%CI 0.46 -0.70, I2=61.1%, high certainty), with maximal benefit in BRCA -mutated (HR 0.40, 95%CI 0.35 -0.45) and homologous recombination -deficient tumours (HR 0.44, 95%CI 0.39 -0.50). BRCA -wildtype disease retained benefit (HR 0.62, 95%CI 0.44 -0.86), whereas homologous r ecombination -proficient tumours did not show a robust advantage."

Clinical • Review • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. (PubMed, J Clin Oncol) - "Cisplatin and gemcitabine is an effective regimen in advanced gBRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in gBRCA/PALB2+ PDAC."

Clinical • Journal • P2 data • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Pancreatic Cancer • Thrombocytopenia • BRCA • BRCA1 • PALB2

Landscape of the Radiosensitizing Properties of Targeted Agents from the NCI CTEP Portfolio across Genomically Diverse 3D Tumor Models (ASTRO 2023) - "PARP inhibitors, of particular interest for clinical translation in this space, demonstrated relatively broad radiosensitization for talazoparib (62%) and olaparib (44%) but less so for veliparib (28%), which correlated with differential PARP trapping potentials. We present a unique resource for examining radiosensitizing drug properties in 3D cultures. The observed radiosensitization patterns strongly argue for the use of larger panels of clinically relevant tumor models rather than a few non-representative cell lines. Our data highlight the urgent need for predictive biomarkers to guide IR/drug combinations, even for some DDR inhibitors."

Preclinical • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • KEAP1 • KRAS • STK11

NAD+ supplementation and PARP inhibition following spinal cord injury in mice: Hurdles and considerations for therapeutic use. (PubMed, Spinal Cord) - "Within the experimental paradigm, neither PARP inhibition nor NAD+ supplementation improved major pathophysiological outcomes associated with an SCI. The results are reviewed in the context of previous reports using PARP inhibition or NAD+ supplementation strategies in SCI. At present, caution is recommended when considering these clinical modalities in treating SCI, and priorities to identify the best therapeutic paradigms are presented."

Journal • Preclinical • Review • CNS Disorders • Orthopedics • GFAP

Efficacy and safety of PARP inhibitors in older patients with advanced ovarian cancer: a systematic review and network meta-analysis. (PubMed, Front Oncol) - "Similar benefits were observed in older patients (≥65 years), with significant PFS improvements for olaparib (HR, 0.44; 95% CI, 0.25-0.77), rucaparib (HR, 0.43; 95% CI, 0.19-0.97), and niraparib (HR, 0.56; 95% CI, 0.38-0.83). In the overall adult population, senaparib, veliparib, and olaparib were associated with significant improvements in PFS...However, treatment was associated with increased hematologic and gastrointestinal toxicities. Further studies should assess geriatric outcomes, long-term safety, and patient-reported outcomes."

Clinical • Journal • Retrospective data • Review • Gynecologic Cancers • Hematological Disorders • Oncology • Ovarian Cancer • Solid Tumor

Biomarker-guided responses in patient-derived organoids predict effective therapies in breast cancer. (PubMed, Cell Rep Med) - P2 | "We utilize patient data from the I-SPY2 clinical trial (NCT01042379) to develop predictive models of response to a range of therapies, using only organoid-detectable biomarkers as input, and validate a model predicting response to veliparib-platinum chemotherapy (VP) in triple-negative BC (TNBC) organoids. A drug screen in VP-resistant TNBC organoids reveals combination treatments that overcome resistance to cisplatin, including pro-apoptotic therapies. Another class of hits, HSP90 inhibitors, links organoid drug sensitivity to improved recurrence-free survival in a biomarker-defined patient subset. These findings establish organoid-based functional modeling as a bridge between clinical biomarkers and precision treatment strategies in breast cancer."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDC37

Veliparib and Dinaciclib in Treating Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=121 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2

Risk of Venous Thromboembolic Events with PARP Inhibitors in Solid Tumour Patients: a Bayesian Network Meta-Analysis (ISTH 2026) - "Compared to control, talazoparib was associated with the highest estimated VTE risk (OR 5.67, 95% CrI 1.62–23.7; SUCRA 93.72), followed by olaparib (OR 2.55, 95% CrI 1.51–4.79; SUCRA 76.80) and niraparib (OR 1.88, 95% CrI 0.27–16.7; SUCRA 59.16). Iniparib (OR 0.99, 95% CrI 0.23–4.79; SUCRA 34.90), veliparib (OR 1.01, 95% CrI 0.61–1.93; SUCRA 34.79), and rucaparib (OR 0.69, 95% CrI 0.29–1.90; SUCRA 16.49) did not demonstrate a significantly increased VTE risk...Clinicians should consider agent-specific thrombotic risk when prescribing PARP inhibitors, and further adequately powered studies are warranted. Table or Figure Upload (1) Page 2 Table or Figure Upload (2) DOI*10.1016/j.rpth.2026.106250 Page 3"

Retrospective data • Cardiovascular • Gastric Cancer • Gastrointestinal Cancer • Oncology • Respiratory Diseases • Solid Tumor

5-FU in combination with PARP inhibitor ABT-888 deregulates MGMT-dependent mismatch repair (MMR) pathway in MMR-proficient colorectal cancer stem cells by modulating MGMT/PARP1/MSH6 complex. (PubMed, Expert Opin Ther Targets) - "Previous study showed the PARP inhibitor ABT-888 potentiates the cytotoxicity of 5-fluorouracil (5-FU) by inhibiting PARP1-mediated mismatch repair (MMR) pathway via MSH6 deregulation in MMR-proficient colorectal cancer stem cells (CRC-CSCs). (9) Consequently, MGMT and MSH6 fail to interact with PARP1, preventing further recruitment of MMR components and leading to defective MGMT-dependent MMR signaling in 5-FU pre-exposed CRC-CSCs, ultimately triggering apoptosis and reducing the cancer stem cell population. Created in BioRender (https://biorender.com/i29644a)."

Journal • Mismatch repair • Colorectal Cancer • Oncology • Solid Tumor • MGMT • MLH1 • MSH2 • MSH6 • PMS2

Talazoparib engages innate immune activation via PARP trapping-dependent cGAS/STING activation in Ewing Sarcoma. (PubMed, Cancer Lett) - "Talazoparib, the strongest PARP-trapping agent, showed markedly greater efficacy than olaparib or veliparib. Combination of talazoparib with exogenous 2'-3'-cyclic GMP-AMP (cGAMP) does not further increase phagocytosis of EwS cells when co-cultured with macrophages, and no additive effects were observed under the tested conditions. Thus, talazoparib is a potent cytotoxic agent with innate immune activation/macrophage-mediated effects, prompting further clinical evaluation in this tumor type."

Journal • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CGAS • STING

Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=156 | Completed | Sponsor: National Cancer Institute (NCI) | Phase classification: P2 ➔ P1/2

Phase classification • Endocrine Cancer • Large Cell Carcinoma • Lung Cancer • Neuroendocrine Carcinoma • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

PARP Trapping as a Therapeutic Vulnerability in ARID1A-Deficient Ovarian Clear Cell Carcinoma (EACR 2026) - "Cells were treated with the alkylating agent methyl methanesulfonate (MMS) in combination with equimolar concentrations of the PARP inhibitors veliparib (weak PARP trapper) or talazoparib (potent PARP trapper). Our study demonstrates that ARID1A deficiency creates a selective sensitivity to PARP trapping, independent of exogenous DNA damage. This mechanistic link between SWI/SNF dysfunction and trapped PARP-DNA complexes suggest a promising therapeutic avenue for ARID1A-mutant OCCC, potentially guiding the rational use of PARP-trapping inhibitors in this challenging cancer subtype."

Clear Cell Carcinoma • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • ARID1A • AVEN • PARP1

Taxane and platinum combination as a predictor of pathologic complete response in I-SPY2 by gene expression breast cancer signatures. (ASCO 2026) - P2 | "Taxane and platinum gene expression signatures showed complementary associations with pCR in the I-SPY2 veliparib-carboplatin arm. Joint modeling and stratification identified subgroups with distinct responses, supporting the potential utility of combining drug-specific biomarkers to refine patient selection for platinum addition in taxane-based NAC."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Autophagy impairs the sensitivity of Ewing sarcoma cells to PARP inhibitors. (PubMed, Cancer Chemother Pharmacol) - "This study demonstrates that autophagy affects the anticancer activity of PARPi in Ewing sarcoma cells."

Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor

Cooperative molecular interaction networks govern PARP1 inhibitor selectivity and binding affinity. (PubMed, PLoS Comput Biol) - "To explore the molecular determinants of ligand selectivity, we focus on four clinically relevant PARP inhibitors-two PARP1-selective (saruparib and NMS-P118) and two non-selective (veliparib and olaparib) inhibitors-and perform atomistic potential-of-mean-force calculations of the PARP1 catalytic binding domain in the presence of these molecules. Progressively increasing the number of mutations markedly reduces binding stability, with distinct residue combinations exerting two primary effects: destabilization of the final bound state and the emergence of energetic barriers along the ligand association pathway. Together, our results provide a coherent mechanistic framework for understanding PARP1 selectivity and informs the rational design of next-generation inhibitors with improved efficacy and safety."

Journal • Hematological Disorders • Oncology • BRCA • PARP2

From DNA repair to neurodegeneration: PARP1 mechanisms and inhibitor strategies in Alzheimer's disease. (PubMed, DNA Repair (Amst)) - "Moreover, brain-penetrant inhibitors such as veliparib and AZD9574 offer enhanced selectivity and access to the central nervous system (CNS). The future calls for CNS-optimized, selective inhibitors that combine safety with bioavailability. This review highlights the exciting possibilities of PARP1 modulation not only for symptomatic relief but also as a marked improvement for the future of treating AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Metabolic Disorders

S1513: FOLFIRI or Modified FOLFIRI and Veliparib as Second Line Therapy in Treating Patients With Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=123 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed

Trial completion • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CEACAM5