Bristol-Myers Squibb Company (NYSE: BMY) today announced clinical results from the QUAZAR AML-001 study, evaluating investigational agent CC-486 as maintenance therapy in a broad population of patients with front-line, newly diagnosed acute myeloid leukemia (AML) who have achieved remission with intensive induction chemotherapy. Data were presented during a late-breaker oral presentation at the 2019 ASH Annual Meeting in Orlando, Fla. In the QUAZAR AML-001 study, treatment with CC-486 in the maintenance setting provided patients a statistically significant and clinically meaningful improvement in overall survival (OS) and relapse-free survival (RFS), as compared to those patients treated with placebo.

Patients in the phase 3, international, randomized, double-blind, placebo-controlled study QUAZAR AML-001 were at least 55 years old, had de novo or secondary AML with intermediate or poor-risk cytogenetics and had achieved their first complete remission (CR) or complete remission with incomplete count recovery (CRi) after intensive induction chemotherapy. Patients had received intensive induction chemotherapy, with or without consolidation chemotherapy per investigator’s choice and were deemed not candidates for hematopoietic stem-cell transplant prior to study entry.

“Despite a number of recent advances in the treatment of AML, the prognosis remains poor, as most patients will relapse and ultimately die of their disease,” said Dr. Andrew Wei, MBBS, Ph.D., from Alfred Hospital and Monash University, Melbourne, Australia. “The role of maintenance therapy in AML has historically been a contentious issue. Based on the results of the QUAZAR study, we are excited about the clinical development of CC-486 and the potential to establish maintenance therapy as a new treatment paradigm for patients with AML in first remission.”

Following intensive induction chemotherapy, 81% of patients had achieved a CR and 19% of patients had achieved a CRi. Eighty percent of patients had received at least one cycle of consolidation therapy prior to enrollment in the study. Four hundred seventy-two patients were then randomized 1:1 to receive initially either investigational CC-486 300mg (n=238) or placebo (n=234) once daily for 14 days of each 28-day cycle. Patients remained on treatment until unacceptable toxicity or disease progression.

At a median follow-up of 41.2 months, the primary endpoint of OS was significantly improved for patients receiving CC-486 compared to placebo. Median OS from time of randomization was 24.7 months in the CC-486 arm compared to 14.8 months for placebo (p=0.0009; HR 0.69 [95% CI: 0.55, 0.86]). Median RFS, the key secondary endpoint, was 10.2 months for those receiving CC-486 compared to 4.8 months for those receiving placebo (p=0.0001; HR 0.65 [95% CI: 0.52, 0.81]). Improvements in OS and RFS for those treated with CC-486 compared to placebo were demonstrated, regardless of cytogenetic risk category, prior consolidation or CR/CRi status at enrollment. Health-related quality of life (HRQoL) was preserved from baseline for patients receiving CC-486 compared to placebo during treatment.

The median duration of treatment was 12 cycles (1-80) for CC-486 and 6 cycles with placebo (1-73). The most commonly occurring adverse events (AEs) of all grades with CC-486 and placebo, respectively, were nausea (65% vs. 24%), vomiting (60% vs. 10%) and diarrhea (50% vs. 22%). The most common grade 3-4 AEs for CC-486 and placebo, respectively, were neutropenia (41% vs. 24%), thrombocytopenia (23% vs. 22%) and anemia (14% vs. 13%). Serious AEs were reported in 34% of CC-486 patients and 25% of placebo patients, and were mainly infections, which occurred in 17% and 8% of CC-486 and placebo patients, respectively. There were 13% of CC-486 patients and 4% of placebo patients who discontinued treatment due to AEs.

“We are extremely encouraged by the results of the QUAZAR AML-001 study as a part of our continuing commitment to both epigenetic research and myeloid diseases,” said Samit Hirawat, M.D., Chief Medical Officer of Bristol-Myers Squibb. “We now look forward to taking the next steps to bring CC-486 to eligible AML patients in need.”

Based on the results of QUAZAR AML-001, Bristol-Myers Squibb is planning regulatory submissions in the first half of 2020.

CC-486 is not approved for any use in any country.