Phase Ib study of CPX-351 lower-intensity therapy (LIT) plus venetoclax as first-line treatment for patients with AML who are unfit for intensive chemotherapy (IC).

Abstract

TPS7567 Background: CPX-351 (Vyxeos; daunorubicin and cytarabine liposome for injection) is approved by the FDA and EMA for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. In a phase 3 study in patients (pts) aged 60-75 y with newly diagnosed high-risk/secondary AML who were fit for IC, CPX-351 significantly improved median survival versus 7+3 cytarabine/daunorubicin and had a comparable safety profile. However, it may not be appropriate to administer CPX-351 at the label dosage in pts unfit for IC. Venetoclax, a BCL-2 inhibitor, has clinical efficacy in combination with low-dose cytarabine in AML pts unfit for IC, and preclinical data suggest a rationale for combining CPX-351 and venetoclax. This study thus evaluates CPX-351 LIT in combination with venetoclax in AML pts unfit for IC. Methods: This is an open-label, multicenter, 2-part, phase 1b study (NCT04038437) to determine the maximum tolerated dose (MTD) and evaluate the safety, efficacy, and pharmacokinetics of CPX-351 LIT plus venetoclax. Key eligibility criteria are shown in the Table. In the dose-escalation phase (3+3 design), up to 24 pts will receive CPX-351 (dose levels: 20, 40, 60, and 75 units/m2) on Days 1 and 3 plus venetoclax 400 mg on Days 2-21 of each cycle to determine the MTD, with each dose escalation confirmed by a safety assessment committee. Pts who achieve complete or partial remission after 1 or 2 cycles may receive up to 4 similar cycles of CPX-351 plus venetoclax. In the expansion phase, an additional 20 pts will be treated at the MTD. All pts are assessed for response by morphology and minimal residual disease testing, and are monitored for safety (until 1 month after end of treatment) and survival (up to 1 year after start of treatment). The study is ongoing and actively enrolling pts. Clinical trial information: NCT04038437 . [Table: see text]