Combination with immune-checkpoint inhibitors
NCT04840589 (enrolling) A Phase I/Ib Trial Evaluating the Safety and Efficacy of BET Inhibitor, ZEN003694 With PD-1 Inhibitor, Nivolumab With or Without CTLA-4 Inhibitor, Ipilimumab in Solid Tumors is evaluating the combination of ZEN-3694 + BMS's immune-checkpoint inhibitors, Opdivo and Yervoy, in patients with advanced or metastatic solid tumors and wildtype BRCA, platinum resistant ovarian cancer. To date, checkpoint inhibitor trials have had limited success in ovarian cancer, and there are few options after patients progress on targeted therapies. ZEN-3694 has been shown preclinically to address several mechanisms of resistance to checkpoint inhibitors, and may sensitize tumors to the checkpoint combination. The trial is being led by
NCT05422794 A Phase 1b Trial of ZEN003694 (ZEN-3694) With Pembrolizumab and Nab-Paclitaxel in Patients With Metastatic Triple-Negative Breast Cancer will evaluate the combination of ZEN-3694 +
Combination with PARP inhibitors
NCT05327010 A Phase 2 Trial of the Combination of the BET Inhibitor, ZEN003694 (ZEN-3694), and the PARP Inhibitor Talazoparib, in Patients With Molecularly-Selected Solid Tumors (ComBET) will evaluate the combination of ZEN-3694 plus talazoparib in additional indications such as PARPi resistant ovarian, prostate cancer, breast, and pancreatic cancers, and solid tumors with Ras alterations. This trial builds on the proof of concept shown in Zenith Epigenetics' mTNBC trial (NCT03901469) by expanding into additional indications where PARPi are utilized. BETi including ZEN-3694 has been shown to sensitize germline BRCA wild-type tumors to PARPi, by creating a 'BRCAness' phenotype and reverse acquired resistance to PARPi in pre-clinical models. The trial will be led by Timothy A Yap, MBBS PhD FRCP, Associate Professor of Investigational Cancer Therapeutics at
Combination with MEK inhibitor
NCT05111561 (enrolling) A Phase 1 Study of ZEN003694 in Combination With Binimetinib in Solid Tumors With RAS Pathway Alterations and Triple Negative Breast Cancer is evaluating the safety and the activity of ZEN-3694 combined with
Combinations with chemotherapy or a CDK4/6 inhibitor for NUT carcinoma
NCT05019716 (enrolling) A Phase 1/2 Study of the Bromodomain Inhibitor ZEN003694 in Combination With Etoposide/Platinum in Patients With NUT Carcinoma is evaluating the combination of ZEN-3694 in combination with chemotherapy in the ultra orphan indication NUT carcinoma. NUT carcinoma is a
NCT05372640 A Phase 1 Study of BET Bromodomain Inhibitor ZEN003694 in Combination With the CDK4/6 Inhibitor Abemaciclib in Patients With NUT Carcinoma and Other Solid Tumors will evaluate the combination of ZEN-3694 and
Combination with an HDAC inhibitor
NCT05053971 (enrolling) A Phase Ib/II Study of ZEN003694 and Entinostat in Advanced and Refractory Solid Tumors and Lymphomas will evaluate the combination of ZEN-3694 and Syndax's HDAC inhibitor, entinostat, in solid tumors and lymphoma, with an expansion population in pancreatic cancer. HDACi have been shown pre-clinically in several systems to sensitize cancer cells to BETi, by hyperacetylating histones, the target of
'We are very pleased with our collaboration with the NCI and that ZEN-3694 will be evaluated in additional oncology indications', said
About Zenith and ZEN-3694
1. Phase 2b metastatic castration resistant prostate (mCRPC) cancer trial in combination with androgen receptor inhibitor, XTANDI (enzalutamide), conducted in collaboration with
2. Phase 2b Triple Negative Breast Cancer (TNBC) trial in combination with the PARP inhibitor TALZENNA (talazoparib), conducted in collaboration with
3. Phase 2 androgen receptor independent mCRPC trial in combination with immune checkpoint inhibitor KEYTRUDA (pembrolizumab) and XTANDI (enzalutamide), conducted by the
About Triple Negative Breast Cancer ('TNBC')
TNBC is an aggressive form of breast cancer with low survival rates. TNBC accounts for about 10-15% of all breast cancers and it differs from other types of invasive breast cancer in that it tends to grow and spread faster, has fewer treatment options, and tends to have a worse prognosis. The term triple-negative breast cancer refers to the fact that the cancer cells have only low or no amount of the receptors ER, PR, and HER2. Approximately 75,000 women in the US,
About Prostate Cancer
Prostate cancer is the second-most commonly diagnosed cancer among men and the fifth most common cause of male cancer death worldwide. Adenocarcinoma of the prostate is dependent on androgen for tumor progression and depleting or blocking androgen action has been a mainstay for over six decades. Although tumors are often initially sensitive to medical or surgical therapies that decrease levels of testosterone and to ARSIs that block AR signaling, disease progression ultimately occurs leading to mCRPC. The treatment of prostate cancer patients has evolved rapidly over the past ten years with second generation ARSIs. Despite these advances, many patients with mCRPC fail or develop resistance to existing treatments, leading to continued disease progression and limited survival rates
About NUT Carcinoma
NUT carcinoma (NC) is a rare, aggressive cancer defined by rearrangements of the NUTM1 gene, most often fusing NUTM1 to a
About Ovarian Cancer
In the US epithelial ovarian cancer is the fifth most common cause of cancer death in women and the most common gynecologic malignancy with about half of women being diagnosed over 65 years of age often with advanced disease. Although primary treatment is effective, most women will relapse and develop resistance to conventional agents.
About Ras activated tumors
Approximately 40% of colorectal cancer, 30% on non-small cell lung cancer, and 95% of pancreatic cancer carry mutations in the oncogene RAS. Ras-mutant cancers are aggressive and poor prognosis, and Ras small molecule inhibitors only target a small percentage of the total Ras-mutant population.
Contact:
Zenith Epigenetics
Phone: 587-390-7865
Email: info@zenithepigenetics.com
Website: www.zenithepigenetics.com
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