Background: HQP1351, a novel, orally active potent 3rd generation TKI, was designed for treatment of patients with chronic myeloid leukemia (CML) resistant to current TKI-therapies including those with T315I mutation. This is an updated report of the safety and efficacy of HQP1351. Methods: It is an open-label, dose escalation and expansion phase 1 trial of HQP1351 which was designed to determine maximum tolerated dose (MTD) and to identify dose-limiting toxicities (DLTs) in patients with CML in the chronic phase (CP) or accelerated phase (AP) resistant or intolerant to ≥ 2 prior TKIs or those with T315I mutation after ≥1 prior TKI. HQP1351 was orally administered once every other day (QOD) in 28-day cycles at 11 dose cohorts ranging from 1mg to 60 mg. The eligible patients received continuous treatments until disease progression to AP or BP, developing intolerant toxicity, consent withdrawal, or death. Blood samples were collected at certain time points on Day 1-2 and Day 27-28 during cycle 1 for PK analyses. Results: From 26 October, 2016 to 27 May, 2019, 101 patients including 87 CP patients and 14 AP patient were enrolled in this study. Seventy-one (70.3%) patients were male. Median duration of follow-up was 12.8 (range, 1.2-31.5) months. Median age was 40 (range, 20-64) years. Median interval from CML diagnosis to starting HQP1351 treatment was 5.8 (range, 0.3-15.2) years. Eighty-three (83.8%) patients received ≥2 prior lines of TKI-therapy. Sixty-two (61.4%) patients harbored T315I mutation. Seventeen patients who initially assigned to the dose escalation cohorts ranging from 1mg to 20 mg moved to 30 mg or higher dose cohorts via intra-patient dose escalation. Fifty-six patients enrolled in the dose expansion part of the trial, including 30mg,40mg and 50mg dose cohorts. Two out of 3 patients at 60mg dose cohort experienced DLT and 50mg QOD was considered as the MTD. During the follow-up period, HQP1351 was well-tolerated in each dose cohort with an exception of 60 mg cohort. All patients experienced ≥1 treatment related adverse events (TRAEs), most of the non-hematologic TRAEs were reported as grade 1 or grade 2. The most common hematologic TRAE of grade 3/4 was thrombocytopenia (49.5%). The incidences of TRAEs tended to be dose-dependent. No death and grade 5 AEs occurred. The incidence of common TRAEs (≥ 10% any grade) are summarized in Table1. HQP1351 showed potent anti-leukemic activities in CML patients. In the 68 evaluable patients with non-CHR at baseline, 63 (92.6%) achieved CHR including 52 out of 55 (94.5%) CP patients and 11 out of 13 (84.6%) AP patients, respectively. In the 95 evaluable patients with non-CCyR at baseline, 56 out of 81 (69.1%) CP patients achieved MCyR including 49 (60.5%) CCyR; and 6 out of 14 (42.9%) AP patients, achieved MCyR including 5 (35.7%) CCyR, respectively. In the 100 evaluable patients, 32 out of 86 (37.2%) CP patients and 5 out of 14 (35.7%) AP patients achieved MMR, respectively. HQP1351 showed highly efficacious in the patients with T315I mutation (Figure A, B). The probability and the depth of response increased with prolonged treatment period (Figure C). As the cut-off date of May 27 2019, 9 patients (5 CP and 4 AP) withdrawn from the study, including progression to AP or BP (n=5), intolerant AEs (n=2), consent withdrawal (n=1), and newly diagnosis of breast cancer (n=1). The progression free survival (PFS) rate at 18-month was 94% in the CP patients and 61% in the AP patients (Figure D). PK analyses indicated an approximately dose proportional increase in exposure (AUC and Cmax) following oral administration of HQP1351 at doses from 1mg to 60 mg. The peak concentration of HQP1351 was reached at 4-8h. The elimination appeared to be linear with a mean terminal T1/2 of 17.5 to 42.5 h. Slight to moderate accumulation was observed on Day 27 following multiple dosing. Reduction of CRkL phosphorylation in PBMCs, a biomarker of BCR-ABL inhibition, has shown to be dose and time dependent in 53 evaluable patients treated with HQP1351. Conclusions: HQP1351 was well tolerated and exhibited significant and durable antitumor activity in the patients with TKI-resistant CML, including those with T315I mutation. Two pivotal studies of HQP1351 in CML-CP and CML-AP patients with T315I mutation are ongoing in China. Disclosures Chen: HealthQuest Pharma Inc.: Employment. Niu:HealthQuest Pharma Inc.: Employment. Men:HealthQuest Pharma Inc.: Employment. Wang:HealthQuest Pharma Inc.: Employment. JI:HealthQuest Pharma Inc.: Employment. Huang:HealthQuest Pharma Inc.: Employment. Yang:Ascentage Pharma Group: Employment. Zhai:Ascentage Pharma Group Inc.: Employment; HealthQuest Pharma Inc.: Employment.

3126 Background: APG-115 is a potent and orally active small-molecule MDM2 protein inhibitor. Binding to MDM2 protein, APG-115 restores p53 tumor suppressive function via induction of apoptosis in tumor cells retaining wild-type p53. In addition, enhanced antitumor activity was demonstrated in the syngeneic tumor models after APG-115 combined with PD-1 blockade. Methods: This Phase I study (APG-115-US-001) was designed to enroll the patients with advanced solid tumors in US (NCT02935907). Study objectives included to assess safety, dose limited toxicity (DLT), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity (assessed every 8 weeks per RECIST v1.1). The patients received APG-115 orally every other day (QOD) at the designated dose (ranging from 10 to 300 mg) for first 21 days of a 28-day cycle, until disease progression. Results: Up until Jan 4 2019, total 28 patients were treated with APG-115 at various doses (one patient at 10mg, 20mg and 50mg, respectively; 14 patients at 100mg, 6 patients at 200mg, and 5 patients at 300mg). The median number of prior systemic anticancer therapies was 4 (range 0-15). The DLTs were observed during cycle 1, including one grade 2 thrombocytopenia at 200mg, one grade 3 thrombocytopenia at 300mg, and one grade 3 fatigue at 100mg and 300mg respectively. The most common AEs (reported in ≥10% of pts) included: fatigue, nausea, vomiting, diarrhea, decreased appetite, dehydration, neutrophil count decreased, white blood cell count decreased, pain in extremity, thrombocytopenia. The most common Grade 3 or 4 treatment related AEs were fatigue (10.7%), and thrombocytopenia (10.7%). Six patients had stable disease (SD) after two cycle treatments, two of them are continuing in this study. PK analyses indicated that exposure (Cmax and AUC) generally increases with the increase of dose level from 20 mg to 300 mg. Conclusions: APG-115 was well tolerated and had manageable adverse events. The MTD/RP2D of APG-115 monotherapy with oral administration, QOD for 21 days of a 28-day cycle for treatment of patients with advanced solid tumors was determined as 100 mg. Further evaluation of APG-115 in combination with pembrolizumab in patients with advanced solid tumors is ongoing. Clinical trial information: NCT02935907.

INTRODUCTION HQP1351 (olverembatinib) is an orally active third-generation BCR-ABL TKI designed for treatment of the patients with CML, harboring T315I mutation, which confers resistance against all first- and second-generation TKIs. METHODS The TKI resistant CML patients harboring T315I mutations either in chronic-phase (CP), or in accelerated-phase (AP), were enrolled into two single-arm, multicenter, open-label pivotal studies: HQP1351-CC201 in and HQP1351-CC202, respectively. The HQP1351 was administered at 40 mg once every other day (QOD) for 28 consecutive days per cycle over 24 months. The primary objective was to evaluate efficacy by major cytogenetic response (MCyR) in patients with CML-CP and major hematologic response (MaHR) in CML-AP. Secondary objectives included safety, tolerability, and pharmacokinetics (PK). RESULTS Baseline characteristics Study CC201 (CML-CP) As of the study cut-off date of March 23, 2020, total 41 patients were enrolled, of whom 38 (92.7%) completed ≥ 6 cycles and 21 (51.2%) were male. Median (range) follow-up was 7.9 (3.1-11.1) months, median age was 47 (22-70) years old. Median (range) interval from CML diagnosis to first HQP1351 treatment was 5.31 (0.6-23.2) years, and 32 (78.1%) patients received ≥ 2 prior lines of TKI. Three patients withdrew from the study-due to progressive disease (PD), intolerance, or consent withdrawal. Study CC202 (CML-AP) As of the cut-off date of February 11, 2020, total 23 patients were enrolled, of whom 18 (78.3%) completed ≥ 6 cycles and 18 (78.3%) were male. Follow-up duration was 8.2 (1.4-9.6) months, median age was 41 (21-74) years old. Median interval from CML diagnosis to first dose of HQP1351 was 4.96 (0.4-10.2) years, and 18 (78.3%) patients received ≥ 2 prior TKIs. Five patients withdrew because of PD or intolerance before Cycle 6. Efficacy Study CC201 (CML-CP) Across a median follow-up of 7.9 months, the mean (95% CI) 3-month progression-free survival (PFS) was 100% (100-100%) and 6-month PFS 96.7% (78.6-99.5%) because of 1 PD. In 31 evaluable patients who did not have a complete hematologic response (CHR) at baseline, 30 (96.8%) achieved CHR. In 41 evaluable patients who did not have a complete CyR (CCyR) at baseline, 31 (75.6%) achieved MCyR, including 27 (65.9%) CCyR and 4 (9.8%) partial CyR (PCyR). Total 20 out of 41 (48.8%) evaluable patients achieved major molecular response (MMR; Figure 1). Study CC202 (CML-AP) Across a median follow-up of 8.2 months, the 3-month PFS was 100% (100-100%) and the 6- month PFS 95.5% (71.9-99.3%) because of 2 PDs. A total of 18 (78.3%) of 23 evaluable patients without MaHR at baseline achieved MaHR, including 14 (60.9%) with CHR. In the 23 evaluable patients without MCyR at baseline, 12 (52.2%) patients achieved MCyR, including 9 (39.1%) CCyR and 3 (13.1%) PCyR. A total of 6 out of 23 (26.1%) evaluable patients achieved MMR (Figure 1). HQP1351 was highly and durably efficacious in the CML patients with T315I mutation; the probability and depth of clinical response may increase with prolonged treatment period. Safety/tolerability Study CC201 Frequent treatment-related adverse events (TRAEs; all grades; G3-4) included thrombocytopenia (65.9%; 48.8%), followed by anemia (48.8%; 24.4%), leukopenia (46.3%; 12.2%), and neutropenia (36.6%; 19.5%). Common non-hematologic TRAEs of any grade included skin pigmentation (53.7%) as well as elevations in creatine kinase (48.8%), ALT (31.7%) and AST (26.8% which most were grade 1 - 2. No death occurred. Study CC202 Common TRAEs (all grades; G3-4; serious AE [SAE]) included thrombocytopenia (73.9%; 52.2%; 17.4%), anemia (65.2%; 39.1%; 13.0%), leukopenia (56.5%; 30.4%; 0%), and neutropenia (26.1%; 21.7%; 0%;). Common non-hematologic AEs included skin pigmentation (69.6%), hypocalcemia (52.2%), proteinuria (52.2%), hypertriglyceridemia (47.8%), hyperphosphatemia (43.5%), arthralgia (34.8%), and fatigue (26.1%), of which most were grade 1- 2. CONCLUSIONS HQP1351 has been shown highly efficacious in heavily TKI-pretreated patients with T315I-mutated CML-CP or CML-AP and was well tolerated. Registration: Clinicaltrials.gov identifier NCT03883087 (Study HQP1351-CC201) NCT03883100 (Study HQP1351-CC202). Disclosures Chen: Ascentage Pharma Group: Current Employment. Niu:Ascentage Pharma Group: Current Employment. Zeng:Ascentage Pharma Group: Current Employment. Men:Ascentage Pharma Group: Current Employment. Lu:Ascentage Pharma Group: Current Employment, Current equity holder in publicly-traded company. Wang:Ascentage Pharma Group: Current Employment. JI:Ascentage Pharma Group: Current Employment. Yue:Ascentage Pharma Group: Current Employment. Yang:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests. Zhai:Ascentage Pharma (SuZhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests.

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Background: Management of CML with TKIs is constrained by treatment resistance, which portends a poor prognosis particularly in pts failing 2 nd-generation TKIs. Cells with BCR-ABL1 T315I mutations are insensitive to 1 st- and 2 nd -generation TKIs, and compound BCR-ABL1 mutations complicate management with all TKIs (including 3 rd-generation ponatinib). Olverembatinib is a novel, potent, 3 rd-generation, orally active BCR-ABL1 TKI with promising activity against CML , largely irrespective of genotype and has a preliminary favorable safety profile. Methods: HQP1351-CC201 and HQP1351-CC202 are Chinese open, single-arm, multicenter phase 2 trials evaluating the safety and efficacy of olverembatinib in adults with TKI-resistant (BCR-ABL1 T351-mutated) CML-CP and CML-CP, respectively. Olverembatinib was administered at 40 mg orally on alternate days for 28-day cycles. The primary outcome measure is major cytogenetic response (MCyR) and major hematologic response (MaHR) by the end of Cycle 12 in CML-CP and CML-AP, respectively. Secondary study endpoints include : complete CyR (CCyR), complete hematologic response (CHR), major molecular response (MMR), progression-free survival (PFS), overall survival (OS), and safety, including treatment-related adverse events (TRAEs) and serious AEs (SAEs). Results: Baseline characteristics Study CC201 （CML-CP ） On the study cutoff date of August 25,2020, 41 pts were enrolled, of whom 32 (78%) completed ≥ 12 cycles and 21 (51.2%) were male. The median (range) follow-up was 13 (3.1-16.3) months, age was 47 (22-70) years, and interval from CML diagnosis to first olverembatinib dose was 5.31 (0.6-23.2) years. In all, 32 (78.1%) pts had received ≥ 2 prior TKIs and 9 pts withdrew because of progressive disease (PD), intolerance, or consent withdrawal before Cycle 12. Study CC202 （CML-AP ） On the cut-off date of July 27, 2020, 23 pts were enrolled, of whom 14 (61%) had completed ≥ 12 cycles and 18 (78.3%) were male. The median (range) follow-up was 13.5 (1.4-15.2) months, age was 41 (21-74) years, and interval from CML diagnosis to first olverembatinib dose was 4.96 (0.4-10.2) years. In all, 18 (78.3%) pts had received ≥ 2 prior TKIs, and 11 pts withdrew because of PD or intolerance before Cycle 12. Efficacy Study CC201 （CML-CP ） After ≥ 12 treatment cycles in pts without responses at baseline, all 31 (100%) experienced CHR (10 other pts had CHR at baseline); 31/41 (75.6%) MCyR; 28/41 (68.3%) CCyR; and 23/41 (56.1%) MMR (Figure 1). The median time to CHR was 1 (95% CI = 1.0-1.9) month, the median time to MCyR was 2.8 (95% CI = 2.8-5.6) months, and the median time to MMR was 6.5 (95% CI = 2.8 to not reached [NR]) months. At 12 months, the PFS rate was 89.3% (95% CI = 73.9%-95.8%), and the OS was 100% (95% CI = 100%-100%). Study CC202 （CML-AP ） After ≥ 12 treatment cycles in pts without responses at baseline, 17/23 (73.9%) experienced MaHR (65.2% CHR and 8.7% no evidence of leukemia [NEL]); 12/23 (52.2%) MCyR; 11/23 (47.8%) CCyR; and 9/23 (39.1%) MMR (Figure 1). The median time to MaHR was 2.8 (95% CI = 1.0-4.7) months, the median time to MCyR was 5.6 (95% CI = 2.00-NR) months, and the median time to MMR was 13.1 (95% CI = 5.6-NR) months. At 12 months, the PFS rate was 74.1% (95% CI = 48.2%-88.4%), and the OS was 91.3% (95% CI = 69.5%-97.8%). Safety Study CC201 （CML-CP ） Frequent TRAEs (all grades; grade 3-4; SAEs) included thrombocytopenia (70.7%; 48.8%; 7.3%), followed by anemia (61%; 26.8%; 2.4%), leukopenia (43.9%; 17.1%; 0), and neutropenia (36.6%; 19.5%; 0). Common nonhematologic TRAEs (all grades; G3-4) included skin pigmentation (56.1%, 0%) and elevations in creatine kinase (51.2%, 14.6%), ALT (39%, 2.4%) and AST (34.1%, 0) (Table 1). No deaths occurred. Study CC202 （CML-AP ） Common TRAEs (all grades; G3-4; SAEs) included thrombocytopenia (73.9%; 56.5%; 17.4%), anemia (60.9%; 34.8%; 13.0%), leukopenia (56.5%; 30.4%; 0), and neutropenia (26.1%; 21.7%; 0). Common nonhematologic AEs included skin pigmentation (69.6%), hypocalcemia (52.2%), proteinuria (47.8%), hypertriglyceridemia (56.5%), hyperphosphatemia (47.8%), hyperuricemia (21.7%), and arthralgia (34.8%), of which most were grade 1-2 (Table 2). Conclusions: Olverembatinib was efficacious and well tolerated when administered as monotherapy in pts with TKI-resistant CP-CML and AP-CML and the BCR-ABL1 T315Imutation. Internal study identifiers: HQP1351-CC201-CC202. ClinicalTrials.gov identifiers: NCT03883087 and NCT03883100. Figure 1 Figure 1. Disclosures Chen: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company. Niu: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company. Men: Ascentage Pharma (Suzhou) Co., Ltd.: Current Employment, Current equity holder in publicly-traded company. Yang: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding. Zhai: Ascentage Pharma Group Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding; Ascentage Pharma (Suzhou) Co., Ltd.: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding.

IntroductionLixisenatide is a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus (T2DM). Its efficacy and safety have been assessed in a series of phase 3 studies included in the GetGoal program. In these studies, lixisenatide was found to be superior to placebo in glycemic control. The aim of this meta-analysis was to assess the safety and efficacy of lixisenatide as an adjunct therapy in Asian patients with T2DM in adequately controlled with oral antidiabetic drugs (OADs).MethodsWe performed a meta-analysis from five lixisenatide phase 3 studies. In each of these multiethnic studies, patients with T2DM inadequately controlled (glycated hemoglobin, HbA1c ≥7%) with established OADs were randomized to lixisenatide or placebo for 24 weeks, with a balanced distribution of Asian patients in these two arms (503 and 338 patients in the intent-to-treat population, respectively).ResultsLixisenatide was superior to placebo in reducing HbA1c (weighted, total mean difference −0.57%; P = 0.002). More patients treated with lixisenatide versus placebo achieved HbA1c targets of ≤7% (49.1% vs. 28.4%, P = 0.003). Lixisenatide was superior to placebo in lowering 2-h postprandial glucose (PPG) (weighted, total mean difference −5.50 mmol/l, P = 0.0005). More patients treated with lixisenatide versus placebo achieved 2-h PPG targets of ≤7.8 mmol/l (39.2% vs. 2.2%, P < 0.0001). More patients treated with lixisenatide versus placebo achieved both an HbA1c target of ≤7% and a 2-h PPG target of ≤10 mmol/l (34.8% vs. 2.69%, P < 0.00001). The body weight of the lixisenatide group tended to decrease. Lixisenatide was generally well tolerated.ConclusionLixisenatide as an adjunct therapy can significantly improve the glycemic control of Asian patients with type 2 DM who do not meet targets for glycemic control with an established OAD regimen.FundingSanofi (China) Investment Co., Ltd., Shanghai, China.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-016-0207-6) contains supplementary material, which is available to authorized users.

Background: Management of CML using TKIs is often constrained by treatment resistance, which portends a poor prognosis. Treatment failure may be due to therapeutic resistance (BCR-ABL1 mutation-dependent or independent), intolerance, and/or suboptimal adherence. The BCR-ABL1 T315I ("gatekeeper") genotype is insensitive to first- and second-generation TKIs, while compound mutations complicate management with all TKIs (including third-generation TKI ponatinib). HQP1351 (olverembatinib) is a novel, third-generation, orally active BCR-ABL1 TKI with evidence of antitumor activity against CML regardless of genotype (Ren X et al. Med Chem 2013;56:879-94) and a preliminary favorable safety profile in clinical trials (Jiang Q et al. Blood 2020;136:50-1). Methods: This Chinese, open label, multicenter, phase 1 trial evaluated the safety and efficacy of olverembatinib in adults with CML in chronic phase (CML-CP) or accelerated phase (CML-AP). Eligible patients have CML-CP or CML-AP that is resistant or intolerant to first- or second-generation TKIs. Patients with severe cardiovascular diseases, hypertension, and pulmonary arterial hypertension were excluded. Olverembatinib is orally administered once every other day in 28-day cycles at 11 dose cohorts ranging from 1 to 60 mg. This study reports data on patients with long-term follow-up. Results: From October 26, 2016, through February 2, 2021 (data cutoff date), 101 patients with CP-CML (n = 86) and AP-CML (n = 15) were enrolled and treated with olverembatinib. Seventy-one (70.3%) patients were male, the median age was 40 (range, 20-64) years, and median (range) interval from diagnosis to initial olverembatinib treatment was 6.0 (0.3-15.2) years. Eighty-four (83.2%) patients received ≥ 2 prior lines of TKI-therapy, and 63 (62.4%) harbored T315I mutation. At baseline, compound mutations were detected in 11 (10.9%) patients, of whom 7 (63.6%) had the BCR-ABL1 T315Igenotype. A total of 20 (19.8%) patients had 2 (n = 13) or ≥ 3 (n = 7) mutations. The median follow-up was 30.8 (1.2-51.8) months. As of the data cutoff date, 81 (80.2%) of 101 patients continued on treatment and 20 (14 CP-CML and 6 AP-CML) discontinued because of disease progression, intolerance, or occurrence of a secondary cancer. The cumulative median (range) drug exposure was 13,635 (1,650-20,975) mg. Of 101 patients, 18 (17.8%) were treated for &gt; 3 years and 5 (5%) for &gt; 4 years. Of evaluable patients without baseline responses, 97.0% had complete hematologic responses (CHR), 62.1% complete cytogenetic responses (CCyR), and 51.0% major molecular responses (MMR). Most evaluable patients with T315I mutations experienced 100% for CHR, 83.7% for MCyR, and 71.2% for MMR among patients in CP-CML, as well as 80.0% for CHR and 54.5% each for MCyR and MMR in AP-CML. At 36 months, the PFS rate (95% CI) was 96.3% (89.1%-98.8%) in patients with CP-CML and 71.4% (40.6%‒88.2%) in those with AP-CML. Treatment responses were durable and unaffected by baseline BCR-ABL1 mutational status. Corresponding values in patients with &gt; 4 years of treatment were 100% (CHR), 80% (CCyR), and 60% (MMR). The mean (95% confidence interval) PFS rate was 100% (100%-100%) at 36 months, 100% at 48 months, and not reached (NR-NR) at 60 months. Most treatment-related adverse events were grade 1 or 2. The most frequent nonhematologic adverse event was (mostly grade 1 or 2) skin hyperpigmentation (86.1%). Grade ≥ 3 nonhematologic AEs included hypertriglyceridemia (10.9%), pyrexia (6.9%), and proteinuria (5.0%). The most common hematologic treatment-related adverse event was thrombocytopenia in 78 (77.2%) patients, including 52 (51.5% of total population) with grade ≥ 3 and 6 (5.9%) with serious adverse events. Leukopenia was grade ≥ 3 in 21 (20.8%) patients but not serious, while anemia was grade 3 or higher in 16 (15.8%) patients and serious in 4 (4.0%). Conclusions: In patients with TKI-resistant CML-CP or CML-AP and long-term treatment, olverembatinib was efficacious and well tolerated. Internal study identifier HQP1351-SJ002. Figure 1 Figure 1. Disclosures Chen: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company. Niu: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company. Men: Ascentage Pharma (Suzhou) Co., Ltd.: Current Employment, Current equity holder in publicly-traded company. Wang: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company. Yang: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding. Zhai: Ascentage Pharma Group Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding; Ascentage Pharma (Suzhou) Co., Ltd.: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding.

IntroductionIn Asia, patients with type 2 diabetes mellitus (T2DM) often have suboptimal glycemic control for many years prior to initiating basal insulin. Active titration of basal insulin is also required to improve glycemic outcomes. This pooled analysis was conducted to determine the impact of patient baseline covariates on the required dose of basal insulin and treatment response, for the improved management of Asian patients with T2DM.MethodsData on insulin-naïve Asian patients with T2DM who initiated and fully titrated insulin glargine 100 U/mL (Gla-100) for ≥ 20 weeks were pooled from seven randomized, controlled, treat-to-target trials. Covariance and multivariate linear/logistic regression analyses were applied to determine the impact of the baseline covariates on Gla-100 dose (primary outcome) and treatment response (secondary outcomes) at week 24 for patients from Asia (N = 724) and from China alone (n = 249). Based on the multivariate analysis for the primary outcome in the Asian population, a nomogram was developed.ResultsThe dose of Gla-100 at week 24 was negatively correlated with age and positively correlated with body mass index (BMI) and fasting plasma glucose (FPG) at baseline in both Asian and Chinese populations. In both populations, higher baseline glycated hemoglobin (HbA1c) was associated with a lower reduction in HbA1c from baseline, higher HbA1c at week 24, and a lower chance of achieving HbA1c < 7% at week 24. The constructed nomogram enables calculation of the likely dose of Gla-100 required by Asian patients with T2DM to achieve HbA1c < 7% at week 24.ConclusionsHigher doses of Gla-100 are likely to be required in younger patients or patients with higher baseline BMI or FPG. The nomogram developed in this study can aid clinicians to titrate the dose of Gla-100 appropriately. Evidence in this pooled analysis also indicates that initiating basal insulin at a lower HbA1c can lead to greater glycemic control.FundingSanofi China Investment Company.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0381-9) contains supplementary material, which is available to authorized users.