A phase III, randomized, multicenter, open-label study of venetoclax or pomalidomide in combination with dexamethasone in patients with t(11;14)-positive relapsed/refractory multiple myeloma
| Autor: | Yao Yu, Paulo Maciag, Maria-Victoria Mateos, Orlando F. Bueno, Scott Cooper, Shaji Kumar, Sudeep Karve, Wan-Jen Hong, Jeremy A. Ross, Emma Arriola, Muhammad Jalaluddin, Philippe Moreau, Meletios A. Dimopoulos, Sheryl Coppola |
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| Rok vydání: | 2020 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Myeloma cell business.industry Venetoclax Pomalidomide medicine.disease 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Open label study 030220 oncology & carcinogenesis Internal medicine Relapsed refractory Medicine In patient business Dexamethasone Multiple myeloma 030215 immunology medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 38:TPS8554-TPS8554 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2020.38.15_suppl.tps8554 |
| Popis: | TPS8554 Background: BCL-2 is an anti-apoptotic protein important for myeloma cell survival. Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor, that has shown promise in clinical studies as monotherapy or in combination with other agents in patients with t(11;14)-positive relapsed/refractory multiple myeloma (RRMM; Kumar et al. Blood. 2017; Costa et al. ASH 2018. Abstr. #303; Harrison et al. ASH 2019. Abstr. #142; Bahlis et al. ASH 2019. Abstr. #925; Kaufman et al. ASH 2019. Abstr. #926). Notably, t(11;14)-positive MM is more dependent on BCL-2 for cell survival, which, together with these clinical data, suggests that Ven combined with dexamethasone (Dex) may provide greater clinical benefit versus standard therapies, like pomalidomide (Pom), in this biomarker-defined patient population. This ongoing Phase 3 study (CANOVA; NCT03539744) aims to evaluate the safety and efficacy of VenDex vs PomDex in t(11;14)-positive RRMM. Methods: Eligible patients (≥18 years) must have t(11;14)-positive RRMM per central lab, an ECOG performance status ≤2, received ≥2 prior lines of therapy, previously received a proteasome inhibitor, and must be refractory to lenalidomide and last line of therapy. Patients cannot have history of treatment with Ven, Pom, or other BCL-2 inhibitors. Patients will be randomized 1:1 to Ven (800 mg orally, once-daily) or Pom (4 mg orally, once-daily on days 1-21 of 28-day cycles). Patients in both groups will receive 40 mg Dex (20 mg for patients ≥75 years) once weekly. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal from study. Patients will be stratified based on age at randomization ( < 65 vs ≥65 years), prior lines of therapy (2 to 3 vs ≥4), and International Staging System stage at screening (I vs II vs III). The primary endpoint is progression-free survival (PFS) per independent review committee (IRC) assessment based on International Myeloma Working Group criteria. The final PFS analysis will be performed when approximately 147 PFS events per IRC are observed. Secondary endpoints are response rate, patient-reported outcomes, overall survival, duration of response, times to response and progression, minimal residual disease negativity rate, safety, and Ven pharmacokinetics. Approximately 244 patients will be enrolled; as of January 21, 2020, 28 patients have been randomized (from 19 sites in 12 countries) and enrollment is ongoing. Clinical trial information: NCT03539744 . |
| Databáze: | OpenAIRE |
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