KEY TAKEAWAYS
- The Phase 3 CANOVA trial aims to evaluate the efficacy and safety of venetoclax in combination with dexamethasone vs. pomalidomide with dexamethasone in t(11;14) RRMM pts.
- The primary endpoint was PFS per IRC assessment. Key secondary endpoints were ORR per IRC, VGPR or better per IRC, OS, MRD negativity rate, and PROs.
- The study examines venetoclax plus dexamethasone as a potential first biomarker-targeted therapy for t(11;14) RRMM. Phase 3 results will be revealed at the upcoming conference.
Venetoclax, a potent inhibitor of BCL-2, has demonstrated both safety and effectiveness in treating t(11;14) relapsed/refractory MM. The CANOVA trial investigates the performance of venetoclax and dexamethasone against pomalidomide and dexamethasone in t(11;14) RRMM patients (pts).
To qualify, participants had to be at least 18 years old, with a confirmed diagnosis of t(11;14)-positive RRMM through centralized FISH and plasma cell enrichment. Additional eligibility criteria included an ECOG performance status of 2 or less, a minimum of two prior lines of therapy, and either progression within 60 days post-treatment or previous receipt of a proteasome inhibitor (PI), with either refractory to or relapse on lenalidomide.
Patients were divided into two treatment arms: venetoclax (800 mg orally once daily, no dose ramp-up) and pomalidomide (4 mg orally from Days 1–21), both with dexamethasone (40 mg weekly). The randomization was stratified based on variables like age, prior lines of treatment, and ISS stage at screening.
The primary endpoint was progression-free survival as assessed by an independent review committee (IRC), with key secondary outcomes including overall response rate, rate of very good partial response or better, overall survival, minimal residual disease negativity rate, and patient-reported outcomes.
As of the March 16, 2023 data cutoff, with a median follow-up period of 21.9 months, 260 pts were randomized, and 254 underwent treatment. Of these, 42% (109 pts) have exited the study. The median age was 66.5 years, ranging from 37 to 89, and 57% were 65 years or older. The gender distribution was 57% male. In terms of race and ethnicity, 68% were White, 30% were Asian, 1% were Black or African American, and 0.4% were Native Hawaiian or Other Pacific Islander. Additionally, 4% identified as Hispanic or Latino. Most pts had an ECOG PS score of 0 (48%) or 1 (44%).
At the initial screening, 74% had undergone 2 to 3 prior lines of therapy (LOTs), and 26% had received 4 or more; 48% were at ISS stage I, 33% at stage II, and 19% at stage III. Most were resistant to proteasome inhibitors (77%) and immunomodulatory drugs (97%, with 96% specifically to lenalidomide). Over a third (37%) were also resistant to anti-CD38 monoclonal antibodies. According to IMWG guidelines, 92% of assessable pts were categorized as standard risk and 8% as high risk. Event-driven primary analysis findings will be disclosed at the upcoming conference.
The CANOVA trial assesses the addition of venetoclax to dexamethasone as a daily oral regimen, marking a potential milestone as the first biomarker-based treatment for t(11;14) RRMM pts. The main findings from this Phase 3 randomized study are yet to be unveiled.
Source: https://imsannual2023.eventscribe.net/fsPopup.asp?PresentationID=1306640&mode=presInfo
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03539744
Mateos, M-V. Results From the Randomized, Open-Label Phase 3 CANOVA Study of Venetoclax Versus Pomalidomide Added to Dexamethasone in Patients With t(11; 14)-Positive Relapsed/Refractory Multiple Myeloma.
