14 CLINICAL STUDIES

The efficacy of ONUREG was evaluated in QUAZAR (NCT01757535), a multicenter, randomized, double-blind, placebo-controlled study. Eligible patients were ages 55 years or older, had AML, and were within 4 months of achieving first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) with intensive induction chemotherapy. Patients may have received consolidation (see Table 4). Patients were excluded if they were candidates for hematopoietic stem cell transplantation at the time of screening.

A total of 472 patients who completed induction with or without consolidation therapy were randomized 1:1 to receive ONUREG 300 mg (n=238) or placebo (n=234) orally on Days 1 through 14 of each 28-day cycle. Randomization was stratified by age at time of induction therapy (55 to 64 vs. ≥ 65 years), cytogenetic risk category at time of induction therapy (intermediate risk vs. poor risk), prior history of MDS/CMML (yes vs. no), and received consolidation therapy following induction therapy (yes vs. no). Baseline demographic and disease characteristics are shown in Table 4.

Table 4: Baseline Demographics and Disease-Related Characteristics in QUAZAR
Parameter	ONUREG (N=238)	Placebo (N=234)
AML=Acute Myeloid Leukemia, MDS=Myelodysplastic Syndrome, CMML=Chronic Myelomonocytic Leukemia, ECOG=Eastern Cooperative Oncology Group, CR=Morphologic Complete Remission, CRi=Morphologic complete remission with incomplete blood count recovery. Source for Intermediate and Poor Risk: National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for Acute Myeloid Leukemia. National Comprehensive Cancer Network website. Available at http://www.nccn.org/professionals/physician_gls/PDF/aml.pdf. Accessed 01 Mar 2011. 1 Intermediate risk was defined as normal cytogenetics +8, t(9;11), or Other undefined. 2 Poor risk was defined as Complex (≥ 3 abnormalities): -5; 5q-; -7; 7q-; 11q23 - non t(9;11); inv(3); t(3;3); t(6;9); or t(9;22).
Age (years)
Median (Min, Max)	68.0 (55, 86)	68.0 (55, 82)
Age Category, n (%)
< 65 years	66 (28)	68 (29)
65 years to < 75 years	144 (61)	142 (61)
≥ 75 years	28 (12)	24 (10)
Sex, n (%)
Male	118 (50)	127 (54)
Female	120 (50)	107 (46)
Race, n (%)
White	216 (91)	197 (84)
Black or African American	2 (1)	6 (3)
Asian	6 (3)	20 (9)
Other	12 (5)	11 (5)
Not Collected or Reported	2 (1)	0 (0)
ECOG Performance Status, n (%)
0	116 (49)	111 (47)
1	101 (42)	106 (45)
2	21 (9)	15 (6)
3	0 (0)	2 (1)
Cytogenetic Risk Status at Diagnosis, n (%)
Intermediate Risk1	203 (85)	203 (87)
Poor Risk2	35 (15)	31 (13)
Initial AML Classification, n (%)
AML with recurrent genetic abnormalities	39 (16)	46 (20)
AML with myelodysplasia-related changes	49 (21)	42 (18)
Therapy related myeloid neoplasms	2 (1)	0 (0)
AML not otherwise specified	148 (62)	145 (62)
Missing	0 (0)	1 (< 1)
Type of AML, n (%)
Primary (de novo)	213 (89)	216 (92)
Secondary	25 (11)	18 (8)
Induction Response
CR	187 (79)	197 (84)
CRi	51 (21)	37 (16)
Consolidation following induction therapy
None	52 (22)	42 (18)
1 cycle	110 (46)	102 (44)
2 cycles	70 (29)	77 (33)
3 cycles	6 (3)	13 (6)
Disease status at study baseline
CR	185 (78)	181 (77)
CRi	44 (18)	38 (16)
Not in CR or CRi	9 (4)	13 (6)
Not Reported	0	2 (1)

The efficacy of ONUREG was established on the basis of overall survival (OS). The trial demonstrated a statistically significant improvement in OS for patients randomized to ONUREG compared to placebo. A subgroup analysis showed consistency in the OS benefit for patients in either CR or CRi. The efficacy results are summarized in Table 5 and Figure 1.

Table 5: Efficacy Results (ITT Population) in QUAZAR
	ONUREG (N=238)	Placebo (N=234)
1 The hazard ratio is from a Cox proportional hazards model stratified by age (55 to 64 vs. ≥65 years), cytogenetic risk category at time of induction therapy (intermediate risk vs. poor risk), and received consolidation therapy (yes vs. no). The p-value is two-sided from a log-rank test stratified by the same factors.
Overall Survival
OS Events, n (%)	158 (66)	171 (73)
Median OS (95% CI) Months	24.7 (18.7, 30.5)	14.8 (11.7, 17.6)
Hazard Ratio (95% CI)1	0.69 (0.55, 0.86)
p value1	0.0009

Figure 1: Kaplan-Meier Curve for Overall Survival (ITT Population) in QUAZAR