Phase 3 Trial for Venetoclax for Multiple Myeloma Misses Its Primary End Point

Abnormal plasma cel in multiple myeloma: ©LASZLO - stock. adobe.com

The phase 3 CANOVA trial (NCT03539744) testing venetoclax (Venclexta) plus dexamethasone in relapsed or refractory multiple myeloma missed its primary end point of progression-free survival (PFS).

Patients who received the venetoclax/dexamethasone combination had a median PFS of 9.9 months compared with 5.8 months when receiving the study comparator pomalidomide (Pomalyst) and dexamethasone combination. These results did not reach statistical significance (HR, 0.823, 95% CI: 0.596-1.136, P=0.237).

"While the CANOVA trial did not meet its primary endpoint, given the potential favorable trends seen in the study, we will discuss these data with health authorities in the near future," said Mariana Cota Stirner, MD, PhD, therapeutic area head oncology hematology, AbbVie, said in a press release. "We remain committed to elevating the standard of care for blood cancer patients around the world including patients with multiple myeloma."

The study’s secondary end points included overall response rate (ORR), very good partial response (VGPR), and overall survival (OS). ORR was 62% in the venetoclax arm vs 25% in the pomalidomide arm. VGPR was 39% in the venetoclax arm vs 14% in the pomalidomide arm. Median OS was 32.4 months in the venetoclax arm vs 24.5 months in the pomalidomide arm (95% CI: 0.472-1.029; p=0.067). The median time to next treatment was longer in the venetoclax arm than the pomalidomide arm, with 21.2 months vs 8.3 months, respectively (HR=0.546, 95% CI: 0.385-0.776; p=0.001).

The safety profile of venetoclax and dexamethasone was consistent with profiles from previous trials, and no new safety signals emerged. The most common adverse event (AE) patients in the venetoclax arm was infection (61%), followed by diarrhea (41%), lymphopenia (24%), and nausea (22%). The most common AEs patients in the pomalidomide arm experienced were neutropenia (63%), infection (57%), thrombocytopenia (39%), and anemia (35%).¹

In order to meet eligibility criteria, patients had to receive 2 prior lines of treatment, receive 2 consecutive cycles of lenalidomide, receive 2 consecutive cycles of a proteasome inhibitor, and have a t(1:14)-positive status. Exclusion criteria included a history of treatment with venetoclax, pomalidomide, or a B-cell lymphoma inhibitor.

In the venetoclax arm, venetoclax was administered orally once daily, and dexamethasone was administered orally once weekly. In the pomalidomide arm, pomalidomide was administered orally once daily for 21 days, and dexamethasone was administered orally once weekly. Both arms operated on 28-day cycles.²

Venetoclax is currently FDA-approved for previously treated and untreated chronic lymphocytic leukemia (CLL) and newly diagnosed acute myeloid leukemia.1 A phase 2 trial evaluating the efficacy of venetoclax in relapsed or refractory CLL or small lymphocytic lymphoma either with a 17p deletion or failure of a B-receptor signaling pathway inhibitor therapy.³

REFERENCES:
1. AbbVie presents results from phase 3 CANOVA study of venetoclax in patients with relapsed or refractory multiple myeloma. News release. September 29, 2023. Accessed October 5, 2023. https://tinyurl.com/32j9dekf

2. A study designed to evaluate the safety and efficacy of venetoclax plus dexamethasone (VenDex) compared with pomalidomide plus dexamethasone (PomDex) in participants with t(11;14)-positive relapsed or refractory multiple myeloma. ClinicalTrials.gov Updated October 2, 2023. Accessed October 5, 2023. https://clinicaltrials.gov/study/NCT03539744

3. A study of venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. ClinicalTrials.gov. Updated July 27, 2023. Accessed October 5, 2023. https://tinyurl.com/35r39ut4