Zentalis's Early WEE1 Inhibitor Data Shows 'Exceptional' Response In Solid Tumor Study, Plans Combination Trials

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  • Zentalis Pharmaceuticals Inc ZNTL has announced initial efficacy and safety data from the Phase 1 dose-escalation portion of its ongoing Phase 1/2 trial evaluating ZN-c3 in patients with advanced solid tumors who are refractory to or ineligible for standard therapy or for whom no standard therapy is available.
  • Data were presented at the American Association of Cancer Research (AACR) Annual Meeting.
  • Zentalis’ WEE1 inhibitor, ZN-c3, posted partial responses across a slate of tumor types with a tolerable safety profile as monotherapy for solid tumor patients.
  • The drug shrank tumors in two patients: One patient had stage 4 ovarian cancer and had tried 18 lines of treatment, while the other patient had stage 4 colorectal cancer and had undergone five prior lines of treatment.
  • The ovarian cancer patient saw targeted tumors shrink by about 56%. Four weeks into treatment, it saw a “large rapid drop” in blood levels of CA-125, an antigen used to monitor certain cancers.
  • As for the colorectal cancer patient, tumors shrank by 42%, and the patient remained on treatment for about six months before the disease progressed.
  • Three other patients had their tumors shrink, too—including one with Stage IV non-small cell lung cancer (NSCLC) and two with uterine serous carcinoma.
  • The NSCLC patient had received three prior lines of therapy and, after ZN-c3 treatment, achieved an unconfirmed partial response with a 50% reduction in overall target lesions.
  • On the safety front, side effects were mostly mild to moderate, with nausea affecting about half of the 55 patients evaluated for safety, diarrhea, fatigue, and vomiting, afflicting less than one-third of them.
  • Blood-related side effects struck less than 10% of patients: 1.8% of patients suffered a low white blood cell count, 7.2% of patients had a low platelet count, and 7.2% of patients developed anemia.
  • The company initiated the Phase 1 expansion portion of the trial with the 300 mg dose earlier in 2021 and is exploring ZN-c3’s potential in combination trials, including in ovarian cancer and osteosarcoma.
  • Separately, the company has collaborated with GlaxoSmithKline plc GSK to evaluate the combination of ZN-c3 and Zejula (niraparib) in patients with advanced epithelial ovarian cancer.
  • Under the terms of the non-exclusive collaboration, Zentalis is responsible for conducting the study with GSK supplying niraparib. Zentalis maintains full ownership of ZN-c3.
  • The company will host a webcast event with key opinion leaders today at 4:00 p.m. ET.
  • Price Action: ZNTL shares are up 7.53% at $40.22 on the last check Monday.
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