KEY TAKEAWAYS
- This Phase 3 randomized, multicenter, open-label study compared the safety and effectiveness of Venetoclax combined with VenDex versus pomalidomide combined with PomDex.
- The trial’s (NCT03539744) primary aim was to assess PFS, which measures the length of time during and after the treatment so that the disease does not worsen.
- Patients meeting specific criteria, including having t(11;14)-positive RRMM and previous lines of therapy, are randomly assigned to receive either Venetoclax or pomalidomide combined with dexamethasone.
- The trial evaluated various endpoints, including PFS, response rate, overall survival, duration of response, times to response and progression, minimum residual disease negativity rate, safety, and Venetoclax pharmacokinetics.
- The study recruited approximately 244 patients, and as of January 21, 2020, 28 patients from 19 sites in 12 countries have been randomized.
- This Phase 3 trial (CANOVA) revealed insights into the safety and efficacy of Venetoclax combined with dexamethasone compared to pomalidomide combined with dexamethasone in patients with t(11;14)-positive RRMM.
BCL-2 is an anti-apoptotic protein essential for myeloma cell survival. Venetoclax (Ven) is a highly selective and 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. The clinical data suggested that Ven combined with dexamethasone (Dex) may provide more clinical benefit than standard therapies like pomalidomide (Pom) in this biomarker-defined patient population.
The current Phase 3 study (CANOVA; NCT03539744) examined how safe and effective VenDex is compared to PomDex in RRMM patients with t(11;14). Patients must be ≥18 years old, have t(11;14)-positive RRMM according to the central lab, have an ECOG performance status of at least ≤2, have had at ≥2 previous lines of therapy, have had a proteasome inhibitor in the past, and be resistant to lenalidomide as their last line of therapy. Patients can’t use Ven, Pom, or other BCL-2 inhibitors. Patients will be given randomized 1:1, 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 get 40 mg of Dex (20 mg for patients ≥75 years) once a week. Treatment will be continued until the sickness worsens, the side effects were too harmful, or the person dropped out of the study.
Patients were added into groups based on their age at selection ( < 65 vs ≥65 years), the number of treatments they’ve already had (2 to 3 vs ≥4), and their International Staging System stage at screening (I vs II vs III). The main goal is progression-free survival (PFS), measured by an independent review committee (IRC) using standards from the International Myeloma Working Group. When about 147 PFS events per IRC have been seen, the final PFS study will be done. Secondary endpoints include response rate, patient-reported outcomes, overall survival, duration of response, times to response and progression, minimum residual disease negativity rate, safety, and Ven pharmacokinetics. About 244 patients will be admitted. As of January 21, 2020, 28 patients from 19 sites in 12 countries have been randomized, and enrollment continues.
Source:https://meetings.asco.org/abstracts-presentations/191904
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03539744
Maria-Victoria Mateos, Philippe Moreau, Meletios A. Dimopoulos, Wan-Jen Hong, Scott Cooper, Yao Yu, Muhammad Jalaluddin, Jeremy A. Ross, Sudeep Karve, Sheryl Coppola, Paulo Cesar Maciag, Orlando Bueno, Emma Louise Arriola, Shaji Kumar/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/J Clin Oncol 38: 2020 (suppl; abstr TPS8554) DOI 10.1200/JCO.2020.38.15_suppl.TPS8554
