Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas

A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMPL-689 in Patients With Relapsed or Refractory Lymphoma

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03786926

Enrollment

Registered

2018-12-26

Start date

2019-08-26

Completion date

2024-06-26

Last updated

2025-06-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma

Keywords

CLL, SLL, FL, MZL, LPL, WM, MCL, PTCL, CBCL

Brief summary

An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas

Detailed description

This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients with relapsed or refractory lymphoma. HMPL-689 is a selective and potent small molecule inhibitor targeting the isoform phosphoinositide 3'-kinase delta (PI3Kδ), a key component in the B-cell receptor signaling pathway This study will consist of a dose escalation stage (Stage 1) and a dose expansion stage (Stage 2). Dose Escalation Stage (Stage 1): This stage will end when any of the following criteria is met: * The dose level 1 demonstrates an excessive toxicity, ie, 3 dose limiting toxicities (DLTs) are observed out of the first 3 patients at dose level 1. * The maximum sample size is reached. * The MTD and/or RP2D is confirmed. Dose Expansion Stage (Stage 2): To further characterize the safety and explore the preliminary anti-tumor activity of HMPL-689 at RP2D, patients with B cell lymphoma will be enrolled in the dose expansion stage.

Interventions

DRUGHMPL-689

HMPL-689 is a PI3Kδ inhibitor

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. (ECOG) performance status of 0 or 1; 2. Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL); 3. Patients with relapsed or refractory NHL for whom: * Standard of care treatment options no longer exist (Stage 1 only); * Standard of care treatment options no longer exist with the exception of PI3K-delta inhibitors (Stage 2 only); 4. Expected survival of more than 24 weeks.

Exclusion criteria

Patients who meet any of the following criteria will be excluded from study entry: 1. Primary central nervous system (CNS) lymphoma; 2. Any of the following laboratory abnormalities Absolute neutrophil count; \<1.0×10\^9/L, Hemoglobin \<80 g/L Platelets \<50 ×10\^9/L 3. Inadequate organ function, defined by the following: * Total bilirubin ≥1.5 times the upper limit of normal (× ULN); * AST or ALT \> 2.5 × ULN; * Estimated creatinine clearance (CrCl) per Cockcroft-Gault; * Dose Escalation stage of trial (Stage 1) - CrCl \< 40 mL/min; * Dose Expansion stage of trial (Stage 2) - CrCl \<30 mL/min; 4. International normalized ratio (INR) \> 1.5 × ULN, activated partial thromboplastin time (aPTT) \> 1.5 × ULN; 5. Serum amylase or lipase \> ULN at screening or known medical history of serum amylase or lipase \> ULN; 6. Patients with presence of second primary malignant tumors within the last 2 years; 7. Clinically significant history of liver disease; 8. Prior treatment with any PI3Kδ inhibitors; 9. Any prior use of the following: cancer therapy within 3 weeks of study treatment, GCSF within 7 days of screening, steroid therapy or targeted anti-neoplastic intent within 7 days of treatment, any use of strong CYP3A4 inducers within 2 weeks prior to initiation of study treatment, prior autologous transplant within 6 months of study treatment, prior allogenic stem cell transplant within 6 months of study treatment; 10. Clinically significant active infection or interstitial lung diseases (including drug induced pneumonitis); 11. Major surgical procedure within 4 weeks prior to initiation of study treatment; 12. Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less than or equal to 1, except for alopecia; 13. New York Heart Association (NYHA) Class II or greater congestive heart failure; 14. Congenital long QT syndrome or QTc \>470 msec; 15. Currently use medication known to cause QT prolongation or torsades de pointes; 16. History of myocardial infarction or unstable angina within 6 months prior to initiation of study treatment; 17. History of stroke or transient ischemic attack within 6 months prior to initiation of study treatment; 18. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease; 19. History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis); 20. Patients with ongoing chronic gastrointestinal diseases; 21. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.

Design outcomes

Primary

Measure	Time frame	Description
Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)	From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 (each cycle is 28 days)	A DLT was defined as the occurrence of any of the following treatment-emergent adverse events (TEAEs) during the DLT assessment window, unless equivocally due to underlying malignancy or an extraneous cause. AEs were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: non-hematologic toxicity: all non-hematologic TEAEs of grade 3 or greater with the exception of grade 3 nausea or vomiting that could be controlled by supportive therapy; hematologic toxicity: grade 4 neutropenia \>5 days, grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding event or requiring platelet transfusion, grade \>=3 febrile neutropenia (defined as absolute neutrophil count \[ANC\] \<1000/cubic millimeter {mm\^3} with a single temperature \>38.3 degree Celsius \[°C\] or a sustained temperature of \>=38°C for more than 1 hour), grade 4 anemia not explained by underlying disease; any TEAE that required a dose delay of \>=15 days; any case of Hy's Law.
Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 34 months	An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. An SAE was an AE that resulted in any of the following: was fatal, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in a neonate/infant born to a female patient or female partner of a male patient exposed to the study drug, or was considered a significant medical event by the investigator. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs and SAEs were defined as AEs and SAEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.
Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 27 months	An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs were defined as AEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.

Secondary

Measure	Time frame	Description
Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months	CBR was defined as percentage of patients who had best overall response (BOR) with stable disease (SD) or better. BOR was defined as the best response recorded from the start of treatment until PD or new anti-cancer therapy, whichever came earlier. PD: \>=25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease. SD: detectable monoclonal IgM, \<25% reduction and \<25% increase in serum IgM level, no progression in extramedullary disease, no new signs/symptoms of active disease.
Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months	PFS was defined as the time from the date of first study drug to the earliest date of PD or death of any cause, whichever occurred first. PD was defined as \>=25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease.
Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose on Days 1, 2, 15, 16, 28 of Cycle 1 and on Day 1 of Cycle 2; 0.5, 1, 2, 4 and 8 hours post-dose on Days 1, 15 and 28 of Cycle 1 (each cycle is 28 days)	Blood samples were collected to determine plasma concentration of HMPL-689. The pharmacokinetic (PK) parameters were determined by non-compartmental analysis.
Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months	ORR: percentage of patients with complete response (CR),CR with incomplete marrow recovery (CRi),nodular partial response (nPR),PR with lymphocytosis (PR-L) or PR for CLL patients; CR, very good PR (VGPR),PR or minor response (MR) for WM patients;CR or PR for patients with disease other than CLL and WM.CR: absence of serum (S) monoclonal immunoglobulin (Ig)M, normal S IgM, complete resolution of extramedullary disease,morphologically normal bone marrow aspirate and trephine biopsy. CRi:criteria fulfilled for CR but persistent cytopenia,anemia,thrombocytopenia or neutropenia. nPR:patients with residual CLL cells.PR-L:patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy.PR, VGPR, MR: detectable monoclonal IgM,no new signs/symptoms of active disease and PR: ≥50% but \<90% reduction in S IgM,reduction in extramedullary disease,VGPR: \>=90% reduction in S IgM,complete resolution of extramedullary disease,MR: \>=25% but \<50% reduction in S IgM.
Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose on Day 1 of Cycles 1, 2, 3, 5, 7, 9, 11, 13 and on Day 15 of Cycle 1; 0 hour on Day 1 of Cycle 1; 1, 2, 3, 4 hours post-dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days)	Blood samples were collected to determine plasma concentration of HMPL-689. The PK parameters were determined by non-compartmental analysis.
Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1 of Cycles 1, 2, 3, 5, 7, 9, 11, 13 and on Day 15 of Cycle 1 (each cycle is 28 days)	Blood samples were collected to determine Ctrough of HMPL-689. The PK parameters were determined by non-compartmental analysis.
Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 and 4 hours on Baseline (Day 1) of Cycle 1; 0, 2 and 4 hours on Day 15 of Cycle 1 (dose escalation phase); 1, 2, 3 and 4 hours on Baseline (Day 1) of Cycle 1; 0, 1, 2, 3, and 4 hours on Day 15 of Cycle 1 (dose expansion phase) (each cycle is 28 days)	12-lead electrocardiogram was performed to evaluate the effect of HMPL-689 on cardiac repolarization by detecting the changes in QTcF intervals. Baseline was defined as the last assessment performed prior to or on first non-zero dose date with time point marked as pre-dose.
Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Days 1, 2, 15, 16, 28 of Cycle 1 and Day 1 of Cycle 2 (each cycle is 28 days)	Blood samples were collected to determine Ctrough of HMPL-689. The PK parameters were determined by non-compartmental analysis.
Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months	TTR was defined as the time from the first dose of study drug to the first occurrence of CR, CRi, PR, nPR, VGPR, PR-L, or MR. CR: absence of serum monoclonal IgM, normal serum IgM, complete resolution of extramedullary disease, morphologically normal bone marrow aspirate and trephine biopsy. CRi: criteria fulfilled for CR but persistent cytopenia, anemia, thrombocytopenia or neutropenia. PR: detectable monoclonal IgM, no new signs/symptoms of active disease, 50% but \<90% reduction in serum IgM, reduction in extramedullary disease. nPR: patients with residual CLL cells. VGPR: detectable monoclonal IgM, no new signs/symptoms of active disease,\>=90% reduction in serum IgM, complete resolution of extramedullary disease. PR-L: patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy. MR: detectable monoclonal IgM, no new signs/symptoms of active disease, \>=25% but \<50% reduction in serum IgM.
Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months	DOR: time from when first response (CR, CRi, PR, nPR, VGPR, PR-L and MR) was achieved until earlier of first documentation of definitive PD or death from any cause, whichever was earlier. CR: absence of S monoclonal IgM, normal S IgM, complete resolution of extramedullary disease, morphologically normal bone marrow aspirate and trephine biopsy. CRi: criteria fulfilled for CR but persistent cytopenia, anemia, thrombocytopenia or neutropenia. nPR: patients with residual CLL cells. PR-L: patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy. PR, VGPR, MR: detectable monoclonal IgM, no new signs/symptoms of active disease and PR: ≥50% but \<90% reduction in S IgM, reduction in extramedullary disease, VGPR: \>=90% reduction in S IgM, complete resolution of extramedullary disease, MR: \>=25% but \<50% reduction in S IgM. PD: \>=25% increase in S IgM level from lowest nadir and/or progression in clinical features attributable to the disease.

Countries

Finland, France, Italy, Poland, Spain, United States

Participant flow

Recruitment details

This Phase 1, 2-part, open-label study was conducted in patients with relapsed, refractory, or resistant lymphoma.

Pre-assignment details

The study consisted of a dose escalation stage (stage 1) and a dose expansion stage (stage 2). A total of 23 patients in dose escalation stage and 30 patients in dose expansion stage were enrolled in this study. The study was terminated based on strategic evaluation of the clinical development of HMPL-689 in the United States, Europe, and Australia with no safety concerns.

Participants by arm

Arm	Count
Dose Escalation Stage: HMPL-689 5 mg QD Patients received HMPL-689 5 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	3
Dose Escalation Stage: HMPL-689 10 mg QD Patients received HMPL-689 10 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	3
Dose Escalation Stage: HMPL-689 15 mg QD Patients received HMPL-689 15 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	5
Dose Escalation Stage: HMPL-689 20 mg QD Patients received HMPL-689 20 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	3
Dose Escalation Stage: HMPL-689 25 mg QD Patients received HMPL-689 25 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	6
Dose Escalation Stage: HMPL-689 30 mg QD Patients received HMPL-689 30 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	3
Dose Expansion Stage: CLL/SLL Patients with CLL/SLL received HMPL-689 at RP2D, that is, 30 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	3
Dose Expansion Stage: FL Patients with FL received HMPL-689 at RP2D, that is, 30 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	13
Dose Expansion Stage: MZL Patient with MZL received HMPL-689 at RP2D, that is, 30 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	6
Dose Expansion Stage: LPL/WM Patients with LPL/WM received HMPL-689 at RP2D, that is, 30 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	3
Dose Expansion Stage: MCL Patients with MCL received HMPL-689 at RP2D, that is, 30 mg QD orally for continuous 28-day treatment cycles until PD, death, intolerable toxicity, investigator's assessment of no benefit from the study treatment, withdrawal from the study, or the end of study, whichever occurred first.	5
Total	53

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010
Overall Study	Adverse Event	0	0	0	0	0	0	0	1	1	0	1
Overall Study	Anti-neoplasm treatment	0	0	0	0	1	0	1	0	0	0	0
Overall Study	Death	0	1	1	0	0	0	0	0	0	1	2
Overall Study	Other	0	0	0	1	0	1	0	0	2	0	0
Overall Study	Physician Decision	0	1	0	1	2	0	0	2	1	1	0
Overall Study	Progressive disease	3	0	3	1	2	2	1	6	1	1	1
Overall Study	Study terminated by Sponsor	0	0	0	0	1	0	0	4	0	0	0
Overall Study	Withdrawal by Subject	0	1	1	0	0	0	1	0	1	0	1

Baseline characteristics

Characteristic	Dose Expansion Stage: MCL	Total	Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: HMPL-689 30 mg QD	Dose Expansion Stage: CLL/SLL	Dose Expansion Stage: FL	Dose Expansion Stage: MZL	Dose Expansion Stage: LPL/WM
Age, Continuous	75.8 years STANDARD_DEVIATION 8.23	66.2 years STANDARD_DEVIATION 10.63	69.7 years STANDARD_DEVIATION 6.51	70.7 years STANDARD_DEVIATION 13.05	64.8 years STANDARD_DEVIATION 17.18	67.7 years STANDARD_DEVIATION 3.51	63.8 years STANDARD_DEVIATION 7.68	59.0 years STANDARD_DEVIATION 17.69	65.7 years STANDARD_DEVIATION 5.03	61.7 years STANDARD_DEVIATION 10.16	72.3 years STANDARD_DEVIATION 9.56	63.7 years STANDARD_DEVIATION 4.16
Race/Ethnicity, Customized Hispanic or Latino	2 Participants	9 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	3 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	3 Participants	43 Participants	3 Participants	1 Participants	5 Participants	3 Participants	5 Participants	3 Participants	3 Participants	10 Participants	4 Participants	3 Participants
Race/Ethnicity, Customized Not Reported	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Other	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White	5 Participants	52 Participants	3 Participants	3 Participants	5 Participants	3 Participants	5 Participants	3 Participants	3 Participants	13 Participants	6 Participants	3 Participants
Sex: Female, Male Female	1 Participants	21 Participants	1 Participants	2 Participants	0 Participants	0 Participants	3 Participants	1 Participants	2 Participants	9 Participants	1 Participants	1 Participants
Sex: Female, Male Male	4 Participants	32 Participants	2 Participants	1 Participants	5 Participants	3 Participants	3 Participants	2 Participants	1 Participants	4 Participants	5 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk
deaths Total, all-cause mortality	0 / 3	1 / 3	1 / 5	0 / 3	0 / 6	0 / 3	0 / 3	0 / 13	0 / 6	1 / 3	2 / 5
other Total, other adverse events	3 / 3	3 / 3	5 / 5	3 / 3	6 / 6	3 / 3	3 / 3	13 / 13	5 / 6	3 / 3	5 / 5
serious Total, serious adverse events	0 / 3	2 / 3	2 / 5	3 / 3	2 / 6	1 / 3	1 / 3	5 / 13	2 / 6	0 / 3	3 / 5

Outcome results

Primary

Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)

A DLT was defined as the occurrence of any of the following treatment-emergent adverse events (TEAEs) during the DLT assessment window, unless equivocally due to underlying malignancy or an extraneous cause. AEs were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: non-hematologic toxicity: all non-hematologic TEAEs of grade 3 or greater with the exception of grade 3 nausea or vomiting that could be controlled by supportive therapy; hematologic toxicity: grade 4 neutropenia \>5 days, grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding event or requiring platelet transfusion, grade \>=3 febrile neutropenia (defined as absolute neutrophil count \[ANC\] \<1000/cubic millimeter {mm\^3} with a single temperature \>38.3 degree Celsius \[°C\] or a sustained temperature of \>=38°C for more than 1 hour), grade 4 anemia not explained by underlying disease; any TEAE that required a dose delay of \>=15 days; any case of Hy's Law.

Time frame: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 (each cycle is 28 days)

Population: The DLT evaluable analysis set (DEAS) was defined as all patients enrolled in the dose escalation stage of the study who were evaluable for DLT assessment. A patient was DLT evaluable if: had received at least 75% of the assigned dose of study drug during the DLT assessment window or had not completed the DLT assessment period due to a DLT.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)	0 Participants
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)	0 Participants
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)	1 Participants
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)	0 Participants
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)	1 Participants
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)	0 Participants

Primary

Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)

An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. An SAE was an AE that resulted in any of the following: was fatal, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in a neonate/infant born to a female patient or female partner of a male patient exposed to the study drug, or was considered a significant medical event by the investigator. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs and SAEs were defined as AEs and SAEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.

Time frame: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 34 months

Population: The FAS included all patients who received at least 1 dose of HMPL-689.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRAE	1 Participants
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRSAE	0 Participants
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TESAE	0 Participants
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TEAE	3 Participants
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRAE	3 Participants
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRSAE	0 Participants
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TESAE	2 Participants
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TEAE	3 Participants
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRSAE	1 Participants
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRAE	4 Participants
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TESAE	2 Participants
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TEAE	5 Participants
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TESAE	3 Participants
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TEAE	3 Participants
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRAE	3 Participants
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRSAE	2 Participants
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRAE	6 Participants
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRSAE	2 Participants
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TESAE	2 Participants
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TEAE	6 Participants
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRSAE	0 Participants
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TEAE	3 Participants
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TRAE	3 Participants
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)	Any TESAE	1 Participants

Primary

Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events

An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs were defined as AEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.

Time frame: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 27 months

Population: The FAS included all patients who received at least 1 dose of HMPL-689.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TRAE	3 Participants
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TEAE	3 Participants
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TRAE	12 Participants
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TEAE	13 Participants
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TEAE	5 Participants
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TRAE	5 Participants
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TEAE	3 Participants
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TRAE	2 Participants
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TRAE	4 Participants
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events	Any TEAE	5 Participants

Secondary

Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)

12-lead electrocardiogram was performed to evaluate the effect of HMPL-689 on cardiac repolarization by detecting the changes in QTcF intervals. Baseline was defined as the last assessment performed prior to or on first non-zero dose date with time point marked as pre-dose.

Time frame: 2 and 4 hours on Baseline (Day 1) of Cycle 1; 0, 2 and 4 hours on Day 15 of Cycle 1 (dose escalation phase); 1, 2, 3 and 4 hours on Baseline (Day 1) of Cycle 1; 0, 1, 2, 3, and 4 hours on Day 15 of Cycle 1 (dose expansion phase) (each cycle is 28 days)

Population: The FAS included all patients who received at least 1 dose of HMPL-689. As pre-specified in the protocol, the results are presented by dose level and combined data for dose expansion stage is presented for all patients evaluable for this endpoint who received HMPL-689 at RP2D (30 mg QD) in dose expansion stage. Only patients with data collected at specified timepoints are reported.

Arm	Measure	Group	Value (MEAN)	Dispersion
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 15 Cycle 1	-13.1 millisecond (msec)	Standard Deviation 12.1
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 1 Cycle 1	-6.89 millisecond (msec)	Standard Deviation 5.68
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 15 Cycle 1	-10.6 millisecond (msec)	Standard Deviation 7.7
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 1 Cycle 1	-8.33 millisecond (msec)	Standard Deviation 7
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	0 hour: Day 15 Cycle 1	-11.3 millisecond (msec)	Standard Deviation 21.7
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	0 hour: Day 15 Cycle 1	-0.333 millisecond (msec)	Standard Deviation 8.49
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 1 Cycle 1	17.3 millisecond (msec)	Standard Deviation 0.471
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 15 Cycle 1	6.67 millisecond (msec)	Standard Deviation 12.7
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 15 Cycle 1	1.50 millisecond (msec)	Standard Deviation 3.06
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 1 Cycle 1	9.67 millisecond (msec)	Standard Deviation 5.66
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	0 hour: Day 15 Cycle 1	-2.17 millisecond (msec)	Standard Deviation 8.72
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 1 Cycle 1	-10.4 millisecond (msec)	Standard Deviation 7.51
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 1 Cycle 1	2.27 millisecond (msec)	Standard Deviation 13.6
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 15 Cycle 1	-0.583 millisecond (msec)	Standard Deviation 5.65
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 15 Cycle 1	-2.17 millisecond (msec)	Standard Deviation 7.33
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	0 hour: Day 15 Cycle 1	-9.83 millisecond (msec)	Standard Deviation 2.59
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 1 Cycle 1	6.11 millisecond (msec)	Standard Deviation 5.82
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 15 Cycle 1	-9.11 millisecond (msec)	Standard Deviation 10.9
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 15 Cycle 1	-7.22 millisecond (msec)	Standard Deviation 7.83
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 1 Cycle 1	-11.5 millisecond (msec)	Standard Deviation 9.19
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 1 Cycle 1	-9.33 millisecond (msec)	Standard Deviation 17.9
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	0 hour: Day 15 Cycle 1	-4.33 millisecond (msec)	Standard Deviation 13.6
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 1 Cycle 1	-13.3 millisecond (msec)	Standard Deviation 13.5
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 15 Cycle 1	-4.27 millisecond (msec)	Standard Deviation 18.8
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 15 Cycle 1	-10.0 millisecond (msec)	Standard Deviation 16.4
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 15 Cycle 1	-11.0 millisecond (msec)	Standard Deviation 11.7
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 1 Cycle 1	-18.5 millisecond (msec)	Standard Deviation 2.59
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	0 hour: Day 15 Cycle 1	-3.50 millisecond (msec)	Standard Deviation 4.01
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 1 Cycle 1	-10.7 millisecond (msec)	Standard Deviation 8.82
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 15 Cycle 1	-14.8 millisecond (msec)	Standard Deviation 10.6
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	1 hour: Day 1 Cycle 1	-5.14 millisecond (msec)	Standard Deviation 10.6
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 15 Cycle 1	-0.964 millisecond (msec)	Standard Deviation 11.2
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	0 hour: Day 15 Cycle 1	0.231 millisecond (msec)	Standard Deviation 11.9
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	3 hours: Day 1 Cycle 1	-2.21 millisecond (msec)	Standard Deviation 9.98
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	1 hour: Day 15 Cycle 1	2.11 millisecond (msec)	Standard Deviation 11.2
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	4 hours: Day 1 Cycle 1	-2.46 millisecond (msec)	Standard Deviation 10.2
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 1 Cycle 1	-1.43 millisecond (msec)	Standard Deviation 9.8
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	2 hours: Day 15 Cycle 1	-0.524 millisecond (msec)	Standard Deviation 9.83
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)	3 hours: Day 15 Cycle 1	0.614 millisecond (msec)	Standard Deviation 8.47

Secondary

Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)

CBR was defined as percentage of patients who had best overall response (BOR) with stable disease (SD) or better. BOR was defined as the best response recorded from the start of treatment until PD or new anti-cancer therapy, whichever came earlier. PD: \>=25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease. SD: detectable monoclonal IgM, \<25% reduction and \<25% increase in serum IgM level, no progression in extramedullary disease, no new signs/symptoms of active disease.

Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months

Population: The EAS included all patients who received at least 1 dose of HMPL-689 and had a baseline tumor assessment and at least 1 evaluable post-baseline assessment unless death occurred before the first post-baseline assessment.

Arm	Measure	Value (NUMBER)
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	100.0 percentage of patients
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	100.0 percentage of patients
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	80.0 percentage of patients
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	100.0 percentage of patients
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	80.0 percentage of patients
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	66.7 percentage of patients
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	100.0 percentage of patients
Dose Expansion Stage: FL	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	84.6 percentage of patients
Dose Expansion Stage: MZL	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	83.3 percentage of patients
Dose Expansion Stage: LPL/WM	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	100.0 percentage of patients
Dose Expansion Stage: MCL	Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)	100.0 percentage of patients

Secondary

Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)

DOR: time from when first response (CR, CRi, PR, nPR, VGPR, PR-L and MR) was achieved until earlier of first documentation of definitive PD or death from any cause, whichever was earlier. CR: absence of S monoclonal IgM, normal S IgM, complete resolution of extramedullary disease, morphologically normal bone marrow aspirate and trephine biopsy. CRi: criteria fulfilled for CR but persistent cytopenia, anemia, thrombocytopenia or neutropenia. nPR: patients with residual CLL cells. PR-L: patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy. PR, VGPR, MR: detectable monoclonal IgM, no new signs/symptoms of active disease and PR: ≥50% but \<90% reduction in S IgM, reduction in extramedullary disease, VGPR: \>=90% reduction in S IgM, complete resolution of extramedullary disease, MR: \>=25% but \<50% reduction in S IgM. PD: \>=25% increase in S IgM level from lowest nadir and/or progression in clinical features attributable to the disease.

Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months

Arm	Measure	Value (MEDIAN)
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	1.9 months
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	31.9 months
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	13.7 months
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	NA months
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	NA months
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	NA months
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	NA months
Dose Expansion Stage: FL	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	NA months
Dose Expansion Stage: MZL	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	NA months
Dose Expansion Stage: LPL/WM	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	NA months
Dose Expansion Stage: MCL	Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)	9.1 months

Secondary

Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)

ORR: percentage of patients with complete response (CR),CR with incomplete marrow recovery (CRi),nodular partial response (nPR),PR with lymphocytosis (PR-L) or PR for CLL patients; CR, very good PR (VGPR),PR or minor response (MR) for WM patients;CR or PR for patients with disease other than CLL and WM.CR: absence of serum (S) monoclonal immunoglobulin (Ig)M, normal S IgM, complete resolution of extramedullary disease,morphologically normal bone marrow aspirate and trephine biopsy. CRi:criteria fulfilled for CR but persistent cytopenia,anemia,thrombocytopenia or neutropenia. nPR:patients with residual CLL cells.PR-L:patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy.PR, VGPR, MR: detectable monoclonal IgM,no new signs/symptoms of active disease and PR: ≥50% but \<90% reduction in S IgM,reduction in extramedullary disease,VGPR: \>=90% reduction in S IgM,complete resolution of extramedullary disease,MR: \>=25% but \<50% reduction in S IgM.

Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months

Population: The efficacy analysis set (EAS) included all patients who received at least 1 dose of HMPL-689 and had a baseline tumor assessment and at least 1 evaluable post-baseline assessment unless death occurred before the first post-baseline assessment.

Arm	Measure	Value (NUMBER)
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	33.3 percentage of patients
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	66.7 percentage of patients
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	80.0 percentage of patients
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	100.0 percentage of patients
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	60.0 percentage of patients
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	66.7 percentage of patients
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	66.7 percentage of patients
Dose Expansion Stage: FL	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	84.6 percentage of patients
Dose Expansion Stage: MZL	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	50.0 percentage of patients
Dose Expansion Stage: LPL/WM	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	100.0 percentage of patients
Dose Expansion Stage: MCL	Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)	100.0 percentage of patients

Secondary

Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)

PFS was defined as the time from the date of first study drug to the earliest date of PD or death of any cause, whichever occurred first. PD was defined as \>=25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease.

Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months

Population: The FAS included all patients who received at least 1 dose of HMPL-689.

Arm	Measure	Value (MEDIAN)
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	5.3 months
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	33.6 months
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	16.6 months
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	NA months
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	13.6 months
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	3.7 months
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	NA months
Dose Expansion Stage: FL	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	11.9 months
Dose Expansion Stage: MZL	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	5.6 months
Dose Expansion Stage: LPL/WM	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	NA months
Dose Expansion Stage: MCL	Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)	10.8 months

Secondary

Dose Escalation and Dose Expansion Stages: Time to Response (TTR)

TTR was defined as the time from the first dose of study drug to the first occurrence of CR, CRi, PR, nPR, VGPR, PR-L, or MR. CR: absence of serum monoclonal IgM, normal serum IgM, complete resolution of extramedullary disease, morphologically normal bone marrow aspirate and trephine biopsy. CRi: criteria fulfilled for CR but persistent cytopenia, anemia, thrombocytopenia or neutropenia. PR: detectable monoclonal IgM, no new signs/symptoms of active disease, 50% but \<90% reduction in serum IgM, reduction in extramedullary disease. nPR: patients with residual CLL cells. VGPR: detectable monoclonal IgM, no new signs/symptoms of active disease,\>=90% reduction in serum IgM, complete resolution of extramedullary disease. PR-L: patients achieved PR with CLL-related signs/symptoms other than lymphocytosis and continued on therapy. MR: detectable monoclonal IgM, no new signs/symptoms of active disease, \>=25% but \<50% reduction in serum IgM.

Time frame: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months

Arm	Measure	Value (MEDIAN)
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	1.87 months
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	1.72 months
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	8.80 months
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	1.77 months
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	2.27 months
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	1.84 months
Dose Expansion Stage: CLL/SLL	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	2.81 months
Dose Expansion Stage: FL	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	1.74 months
Dose Expansion Stage: MZL	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	2.53 months
Dose Expansion Stage: LPL/WM	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	3.73 months
Dose Expansion Stage: MCL	Dose Escalation and Dose Expansion Stages: Time to Response (TTR)	1.76 months

Secondary

Dose Escalation Stage: Plasma Concentration of HMPL-689

Blood samples were collected to determine plasma concentration of HMPL-689. The pharmacokinetic (PK) parameters were determined by non-compartmental analysis.

Time frame: Pre-dose on Days 1, 2, 15, 16, 28 of Cycle 1 and on Day 1 of Cycle 2; 0.5, 1, 2, 4 and 8 hours post-dose on Days 1, 15 and 28 of Cycle 1 (each cycle is 28 days)

Population: The pharmacokinetic analysis set (PKAS) included all patients who received at least 1 dose of HMPL-689 and had at least 1 PK sample obtained and analyzed. Only patients with data collected at specified timepoints are reported.

Arm	Measure	Group	Value (MEAN)	Dispersion
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	8.593 nanograms per milliliter (ng/mL)	Standard Deviation 4.588
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	22.200 nanograms per milliliter (ng/mL)	Standard Deviation 4.629
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 15 Cycle 1	15.933 nanograms per milliliter (ng/mL)	Standard Deviation 2.307
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 28 Cycle 1	16.700 nanograms per milliliter (ng/mL)	Standard Deviation 3.341
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 2 Cycle 1	4.490 nanograms per milliliter (ng/mL)	Standard Deviation 1.36
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 nanograms per milliliter (ng/mL)	Standard Deviation 0
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 1 Cycle 1	15.100 nanograms per milliliter (ng/mL)	Standard Deviation 4.19
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	19.267 nanograms per milliliter (ng/mL)	Standard Deviation 4.186
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	20.323 nanograms per milliliter (ng/mL)	Standard Deviation 11.02
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 1 Cycle 1	1.153 nanograms per milliliter (ng/mL)	Standard Deviation 1.22
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 28 Cycle 1	25.767 nanograms per milliliter (ng/mL)	Standard Deviation 2.05
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 28 Cycle 1	21.803 nanograms per milliliter (ng/mL)	Standard Deviation 15.134
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 28 Cycle 1	24.473 nanograms per milliliter (ng/mL)	Standard Deviation 29.361
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 16 Cycle 1	5.567 nanograms per milliliter (ng/mL)	Standard Deviation 0.958
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 28 Cycle 1	5.837 nanograms per milliliter (ng/mL)	Standard Deviation 1.257
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	31.123 nanograms per milliliter (ng/mL)	Standard Deviation 24.388
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	14.457 nanograms per milliliter (ng/mL)	Standard Deviation 14.965
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 28 Cycle 1	17.383 nanograms per milliliter (ng/mL)	Standard Deviation 22.271
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	19.300 nanograms per milliliter (ng/mL)	Standard Deviation 26.414
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 15 Cycle 1	5.443 nanograms per milliliter (ng/mL)	Standard Deviation 2.145
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	4.580 nanograms per milliliter (ng/mL)	Standard Deviation 0.521
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	79.867 nanograms per milliliter (ng/mL)	Standard Deviation 23.5
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 28 Cycle 1	10.885 nanograms per milliliter (ng/mL)	Standard Deviation 1.86
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 28 Cycle 1	61.550 nanograms per milliliter (ng/mL)	Standard Deviation 14.779
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 28 Cycle 1	101.100 nanograms per milliliter (ng/mL)	Standard Deviation 56.427
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	17.500 nanograms per milliliter (ng/mL)	Standard Deviation 7.292
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 28 Cycle 1	110.300 nanograms per milliliter (ng/mL)	Standard Deviation 46.245
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	71.346 nanograms per milliliter (ng/mL)	Standard Deviation 63.493
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	50.887 nanograms per milliliter (ng/mL)	Standard Deviation 41.833
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	44.467 nanograms per milliliter (ng/mL)	Standard Deviation 22.299
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 nanograms per milliliter (ng/mL)	Standard Deviation 0
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 1 Cycle 1	35.867 nanograms per milliliter (ng/mL)	Standard Deviation 9.063
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 28 Cycle 1	32.700 nanograms per milliliter (ng/mL)	Standard Deviation 4.667
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 2 Cycle 1	11.527 nanograms per milliliter (ng/mL)	Standard Deviation 6.411
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	35.613 nanograms per milliliter (ng/mL)	Standard Deviation 39.872
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 15 Cycle 1	118.433 nanograms per milliliter (ng/mL)	Standard Deviation 82.709
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	115.400 nanograms per milliliter (ng/mL)	Standard Deviation 69.73
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 28 Cycle 1	55.750 nanograms per milliliter (ng/mL)	Standard Deviation 22.698
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	56.200 nanograms per milliliter (ng/mL)	Standard Deviation 22.311
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 1 Cycle 1	65.133 nanograms per milliliter (ng/mL)	Standard Deviation 72.976
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 15 Cycle 1	37.533 nanograms per milliliter (ng/mL)	Standard Deviation 16.861
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 16 Cycle 1	61.367 nanograms per milliliter (ng/mL)	Standard Deviation 87.227
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 2 Cycle 1	12.442 nanograms per milliliter (ng/mL)	Standard Deviation 5.112
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	98.260 nanograms per milliliter (ng/mL)	Standard Deviation 16.955
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 15 Cycle 1	73.233 nanograms per milliliter (ng/mL)	Standard Deviation 14.758
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	12.450 nanograms per milliliter (ng/mL)	Standard Deviation 9.931
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 15 Cycle 1	44.295 nanograms per milliliter (ng/mL)	Standard Deviation 40.717
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	17.880 nanograms per milliliter (ng/mL)	Standard Deviation 7.265
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 28 Cycle 1	111.950 nanograms per milliliter (ng/mL)	Standard Deviation 33.596
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	66.740 nanograms per milliliter (ng/mL)	Standard Deviation 41.46
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 1 Cycle 1	19.322 nanograms per milliliter (ng/mL)	Standard Deviation 18.574
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	66.900 nanograms per milliliter (ng/mL)	Standard Deviation 50.101
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 28 Cycle 1	56.150 nanograms per milliliter (ng/mL)	Standard Deviation 51.474
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	86.425 nanograms per milliliter (ng/mL)	Standard Deviation 42.718
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 28 Cycle 1	39.950 nanograms per milliliter (ng/mL)	Standard Deviation 37.487
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 28 Cycle 1	19.575 nanograms per milliliter (ng/mL)	Standard Deviation 9.215
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	91.625 nanograms per milliliter (ng/mL)	Standard Deviation 31.814
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	95.260 nanograms per milliliter (ng/mL)	Standard Deviation 33.323
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 28 Cycle 1	108.175 nanograms per milliliter (ng/mL)	Standard Deviation 39.401
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 28 Cycle 1	62.750 nanograms per milliliter (ng/mL)	Standard Deviation 21.418
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 16 Cycle 1	17.825 nanograms per milliliter (ng/mL)	Standard Deviation 4.234
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 1 Cycle 1	48.440 nanograms per milliliter (ng/mL)	Standard Deviation 18.373
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 nanograms per milliliter (ng/mL)	Standard Deviation 0
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	67.367 nanograms per milliliter (ng/mL)	Standard Deviation 30.596
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 2 Cycle 1	8.887 nanograms per milliliter (ng/mL)	Standard Deviation 4.148
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 nanograms per milliliter (ng/mL)	Standard Deviation 0
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 1 Cycle 1	36.700 nanograms per milliliter (ng/mL)	Standard Deviation 13.981
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 16 Cycle 1	15.100 nanograms per milliliter (ng/mL)	Standard Deviation 1.556
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	102.900 nanograms per milliliter (ng/mL)	Standard Deviation 22.999
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 28 Cycle 1	67.000 nanograms per milliliter (ng/mL)	Standard Deviation 66.731
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	11.100 nanograms per milliliter (ng/mL)	Standard Deviation 10.026
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	19.200 nanograms per milliliter (ng/mL)	Standard Deviation 2.121
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 28 Cycle 1	115.000 nanograms per milliliter (ng/mL)	Standard Deviation 22.068
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	125.100 nanograms per milliliter (ng/mL)	Standard Deviation 78.083
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 15 Cycle 1	58.450 nanograms per milliliter (ng/mL)	Standard Deviation 9.122
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 28 Cycle 1	126.500 nanograms per milliliter (ng/mL)	Standard Deviation 78.665
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 15 Cycle 1	59.667 nanograms per milliliter (ng/mL)	Standard Deviation 52.905
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 1 Cycle 1	87.733 nanograms per milliliter (ng/mL)	Standard Deviation 68.441
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 28 Cycle 1	66.867 nanograms per milliliter (ng/mL)	Standard Deviation 14.23
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 28 Cycle 1	25.133 nanograms per milliliter (ng/mL)	Standard Deviation 7.251
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	97.667 nanograms per milliliter (ng/mL)	Standard Deviation 14.468
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	108.067 nanograms per milliliter (ng/mL)	Standard Deviation 27.749
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	100.667 nanograms per milliliter (ng/mL)	Standard Deviation 63.801
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 28 Cycle 1	113.333 nanograms per milliliter (ng/mL)	Standard Deviation 85.096
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	94.420 nanograms per milliliter (ng/mL)	Standard Deviation 72.734
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 nanograms per milliliter (ng/mL)	Standard Deviation 0
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 1 Cycle 1	47.424 nanograms per milliliter (ng/mL)	Standard Deviation 78.327
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	110.780 nanograms per milliliter (ng/mL)	Standard Deviation 70.347
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	141.600 nanograms per milliliter (ng/mL)	Standard Deviation 82.032
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	103.700 nanograms per milliliter (ng/mL)	Standard Deviation 33.787
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 1 Cycle 1	68.120 nanograms per milliliter (ng/mL)	Standard Deviation 27.164
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 2 Cycle 1	20.017 nanograms per milliliter (ng/mL)	Standard Deviation 8.614
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	29.250 nanograms per milliliter (ng/mL)	Standard Deviation 14.562
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 15 Cycle 1	45.180 nanograms per milliliter (ng/mL)	Standard Deviation 29.456
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	122.220 nanograms per milliliter (ng/mL)	Standard Deviation 86.832
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	153.400 nanograms per milliliter (ng/mL)	Standard Deviation 30.345
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 15 Cycle 1	87.620 nanograms per milliliter (ng/mL)	Standard Deviation 26.685
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 16 Cycle 1	31.320 nanograms per milliliter (ng/mL)	Standard Deviation 13.989
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 28 Cycle 1	32.380 nanograms per milliliter (ng/mL)	Standard Deviation 17.181
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 28 Cycle 1	42.940 nanograms per milliliter (ng/mL)	Standard Deviation 18.447
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 28 Cycle 1	101.740 nanograms per milliliter (ng/mL)	Standard Deviation 64.018
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 28 Cycle 1	149.460 nanograms per milliliter (ng/mL)	Standard Deviation 74.134
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 28 Cycle 1	145.720 nanograms per milliliter (ng/mL)	Standard Deviation 57.106
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 28 Cycle 1	97.560 nanograms per milliliter (ng/mL)	Standard Deviation 29.737
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	30.400 nanograms per milliliter (ng/mL)	Standard Deviation 13.557
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 15 Cycle 1	77.367 nanograms per milliliter (ng/mL)	Standard Deviation 25.143
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 nanograms per milliliter (ng/mL)	Standard Deviation 0
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 28 Cycle 1	219.250 nanograms per milliliter (ng/mL)	Standard Deviation 186.323
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	158.833 nanograms per milliliter (ng/mL)	Standard Deviation 63.135
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	187.333 nanograms per milliliter (ng/mL)	Standard Deviation 88.636
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 15 Cycle 1	21.733 nanograms per milliliter (ng/mL)	Standard Deviation 9.166
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	22.900 nanograms per milliliter (ng/mL)	Standard Deviation 11.077
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	116.667 nanograms per milliliter (ng/mL)	Standard Deviation 16.773
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 28 Cycle 1	133.333 nanograms per milliliter (ng/mL)	Standard Deviation 17.559
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 2 Cycle 1	13.433 nanograms per milliliter (ng/mL)	Standard Deviation 1.501
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 1 Cycle 1	72.600 nanograms per milliliter (ng/mL)	Standard Deviation 19.128
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	111.533 nanograms per milliliter (ng/mL)	Standard Deviation 49.843
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	167.033 nanograms per milliliter (ng/mL)	Standard Deviation 75.883
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	16.833 nanograms per milliliter (ng/mL)	Standard Deviation 5.341
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	8 hours post-dose: Day 28 Cycle 1	81.533 nanograms per milliliter (ng/mL)	Standard Deviation 12.052
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	184.000 nanograms per milliliter (ng/mL)	Standard Deviation 176.952
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 1 Cycle 1	36.907 nanograms per milliliter (ng/mL)	Standard Deviation 32.999
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 28 Cycle 1	140.533 nanograms per milliliter (ng/mL)	Standard Deviation 137.107
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	0.5 hour post-dose: Day 28 Cycle 1	24.367 nanograms per milliliter (ng/mL)	Standard Deviation 16.404
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 28 Cycle 1	21.200 nanograms per milliliter (ng/mL)	Standard Deviation 10.121
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 16 Cycle 1	20.267 nanograms per milliliter (ng/mL)	Standard Deviation 9.393

Secondary

Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689

Blood samples were collected to determine Ctrough of HMPL-689. The PK parameters were determined by non-compartmental analysis.

Time frame: Days 1, 2, 15, 16, 28 of Cycle 1 and Day 1 of Cycle 2 (each cycle is 28 days)

Population: The PKAS included all patients who received at least 1 dose of HMPL-689 and had at least 1 PK sample obtained and analyzed. Only patients with data collected at specified timepoints are reported.

Arm	Measure	Group	Value (MEAN)	Dispersion
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 15: Cycle 1	4.580 ng/mL	Standard Deviation 0.521
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 2: Cycle 1	4.490 ng/mL	Standard Deviation 1.36
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 28: Cycle 1	5.837 ng/mL	Standard Deviation 1.257
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 16: Cycle 1	5.567 ng/mL	Standard Deviation 0.958
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 1: Cycle 2	6.140 ng/mL	Standard Deviation 2.447
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 2: Cycle 1	8.290 ng/mL	Standard Deviation 4.398
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 1: Cycle 2	17.500 ng/mL	Standard Deviation 7.292
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 15: Cycle 1	35.613 ng/mL	Standard Deviation 39.872
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 16: Cycle 1	11.050 ng/mL	Standard Deviation 5.162
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 28: Cycle 1	10.885 ng/mL	Standard Deviation 1.86
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 15: Cycle 1	16.600 ng/mL	Standard Deviation 6.678
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 16: Cycle 1	17.825 ng/mL	Standard Deviation 4.234
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 2: Cycle 1	12.442 ng/mL	Standard Deviation 5.112
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 1: Cycle 2	17.880 ng/mL	Standard Deviation 7.265
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 28: Cycle 1	19.575 ng/mL	Standard Deviation 9.215
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 15: Cycle 1	16.650 ng/mL	Standard Deviation 4.031
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 28: Cycle 1	25.133 ng/mL	Standard Deviation 7.251
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 2: Cycle 1	8.887 ng/mL	Standard Deviation 4.148
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 1: Cycle 2	19.200 ng/mL	Standard Deviation 2.121
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 28: Cycle 1	32.380 ng/mL	Standard Deviation 17.181
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 15: Cycle 1	31.160 ng/mL	Standard Deviation 15.418
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 16: Cycle 1	31.320 ng/mL	Standard Deviation 13.989
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 2: Cycle 1	20.017 ng/mL	Standard Deviation 8.614
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 1: Cycle 2	30.400 ng/mL	Standard Deviation 13.557
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 1: Cycle 2	16.833 ng/mL	Standard Deviation 5.341
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 2: Cycle 1	13.433 ng/mL	Standard Deviation 1.501
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 15: Cycle 1	22.900 ng/mL	Standard Deviation 11.077
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 16: Cycle 1	20.267 ng/mL	Standard Deviation 9.393
Dose Escalation Stage: HMPL-689 30 mg QD	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 28: Cycle 1	21.200 ng/mL	Standard Deviation 10.121
Unknown	Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689	Day 1: Cycle 1	— ng/mL	—

Secondary

Dose Expansion Stage: Plasma Concentration of HMPL-689

Blood samples were collected to determine plasma concentration of HMPL-689. The PK parameters were determined by non-compartmental analysis.

Time frame: Pre-dose on Day 1 of Cycles 1, 2, 3, 5, 7, 9, 11, 13 and on Day 15 of Cycle 1; 0 hour on Day 1 of Cycle 1; 1, 2, 3, 4 hours post-dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days)

Arm	Measure	Group	Value (MEAN)	Dispersion
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 9	NA ng/mL	—
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 11	NA ng/mL	—
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	104.233 ng/mL	Standard Deviation 117.306
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	233.667 ng/mL	Standard Deviation 2.082
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	111.833 ng/mL	Standard Deviation 22.661
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 3	32.633 ng/mL	Standard Deviation 15.667
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 15 Cycle 1	179.000 ng/mL	Standard Deviation 30.447
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 1 Cycle 1	101.967 ng/mL	Standard Deviation 70.324
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	142.967 ng/mL	Standard Deviation 119.865
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	22.933 ng/mL	Standard Deviation 8.804
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	NA ng/mL	—
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 5	NA ng/mL	—
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 7	NA ng/mL	—
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	140.667 ng/mL	Standard Deviation 48.003
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	54.743 ng/mL	Standard Deviation 85.161
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 ng/mL	Standard Deviation 0
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	146.358 ng/mL	Standard Deviation 92.001
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	61.493 ng/mL	Standard Deviation 69.318
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 5	82.100 ng/mL	Standard Deviation 55.917
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	0 hour post-dose: Day 1 Cycle 1	48.400 ng/mL	Standard Deviation 61.06
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 11	NA ng/mL	—
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	108.857 ng/mL	Standard Deviation 74.766
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	150.523 ng/mL	Standard Deviation 51.261
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 13	NA ng/mL	—
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 1 Cycle 1	130.742 ng/mL	Standard Deviation 54.78
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 9	49.400 ng/mL	Standard Deviation 46.088
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	117.708 ng/mL	Standard Deviation 62.408
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	148.333 ng/mL	Standard Deviation 44.252
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	37.056 ng/mL	Standard Deviation 22.923
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 3	39.367 ng/mL	Standard Deviation 36.625
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	193.417 ng/mL	Standard Deviation 92.573
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 15 Cycle 1	166.550 ng/mL	Standard Deviation 65.746
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	1.685 ng/mL	Standard Deviation 6.074
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 7	NA ng/mL	—
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 13	NA ng/mL	—
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	31.363 ng/mL	Standard Deviation 25.923
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	123.483 ng/mL	Standard Deviation 48.346
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 3	41.815 ng/mL	Standard Deviation 34.757
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 ng/mL	Standard Deviation 0
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	125.917 ng/mL	Standard Deviation 52.229
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	30.666 ng/mL	Standard Deviation 23.182
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 7	23.983 ng/mL	Standard Deviation 35.772
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 1 Cycle 1	131.600 ng/mL	Standard Deviation 33.368
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 9	NA ng/mL	—
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 5	40.412 ng/mL	Standard Deviation 40.658
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	171.000 ng/mL	Standard Deviation 71.632
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 15 Cycle 1	140.867 ng/mL	Standard Deviation 56.317
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	108.833 ng/mL	Standard Deviation 30.521
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	167.433 ng/mL	Standard Deviation 71.148
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	145.600 ng/mL	Standard Deviation 131.539
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 11	NA ng/mL	—
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 ng/mL	Standard Deviation 0
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	86.950 ng/mL	Standard Deviation 93.589
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	136.333 ng/mL	Standard Deviation 114.031
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 1 Cycle 1	98.267 ng/mL	Standard Deviation 70.926
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	72.933 ng/mL	Standard Deviation 37.302
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	16.667 ng/mL	Standard Deviation 16.22
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	95.467 ng/mL	Standard Deviation 66.718
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	128.000 ng/mL	Standard Deviation 88.705
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 15 Cycle 1	95.333 ng/mL	Standard Deviation 38.783
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	85.167 ng/mL	Standard Deviation 35.335
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	15.237 ng/mL	Standard Deviation 5.614
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 3	12.890 ng/mL	Standard Deviation 8.707
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 5	NA ng/mL	—
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 7	19.733 ng/mL	Standard Deviation 11.057
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 9	18.533 ng/mL	Standard Deviation 10.883
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 11	NA ng/mL	—
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 13	NA ng/mL	—
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 15 Cycle 1	165.000 ng/mL	Standard Deviation 75.024
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 15 Cycle 1	180.800 ng/mL	Standard Deviation 87.697
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 15 Cycle 1	115.880 ng/mL	Standard Deviation 147.709
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 7	75.967 ng/mL	Standard Deviation 54.444
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 1 Cycle 1	119.720 ng/mL	Standard Deviation 36.898
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	3 hours post-dose: Day 1 Cycle 1	116.667 ng/mL	Standard Deviation 11.93
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 1 Cycle 1	132.460 ng/mL	Standard Deviation 27.338
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	2 hours post-dose: Day 15 Cycle 1	190.400 ng/mL	Standard Deviation 53.003
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 9	NA ng/mL	—
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	1 hour post-dose: Day 1 Cycle 1	75.750 ng/mL	Standard Deviation 33.441
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	0 hour post-dose: Day 1 Cycle 1	NA ng/mL	—
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 3	43.800 ng/mL	Standard Deviation 13.444
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 2	37.060 ng/mL	Standard Deviation 25.195
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 1	0.000 ng/mL	Standard Deviation 0
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	Pre-dose: Day 1 Cycle 5	25.167 ng/mL	Standard Deviation 25.877
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Concentration of HMPL-689	4 hours post-dose: Day 15 Cycle 1	153.520 ng/mL	Standard Deviation 46.202

Secondary

Dose Expansion Stage: Plasma Trough Concentration of HMPL-689

Blood samples were collected to determine Ctrough of HMPL-689. The PK parameters were determined by non-compartmental analysis.

Time frame: Day 1 of Cycles 1, 2, 3, 5, 7, 9, 11, 13 and on Day 15 of Cycle 1 (each cycle is 28 days)

Arm	Measure	Group	Value (MEAN)	Dispersion
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 11	28.100 ng/mL	—
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 2	24.550 ng/mL	Standard Deviation 2.758
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 7	34.050 ng/mL	Standard Deviation 6.293
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 9	37.400 ng/mL	—
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 15: Cycle 1	22.933 ng/mL	Standard Deviation 8.804
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 3	23.750 ng/mL	Standard Deviation 4.172
Dose Escalation Stage: HMPL-689 5 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 5	36.450 ng/mL	Standard Deviation 15.627
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 3	46.214 ng/mL	Standard Deviation 38.254
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 13	29.600 ng/mL	—
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 15: Cycle 1	37.056 ng/mL	Standard Deviation 22.923
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 2	41.013 ng/mL	Standard Deviation 36.989
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 11	24.100 ng/mL	—
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 5	63.625 ng/mL	Standard Deviation 43.513
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 7	27.950 ng/mL	Standard Deviation 9.829
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 1	21.900 ng/mL	—
Dose Escalation Stage: HMPL-689 10 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 9	59.050 ng/mL	Standard Deviation 60.74
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 3	33.587 ng/mL	Standard Deviation 37.495
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 7	32.550 ng/mL	Standard Deviation 46.033
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 11	65.200 ng/mL	—
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 5	49.225 ng/mL	Standard Deviation 41.065
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 2	30.666 ng/mL	Standard Deviation 23.182
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 9	61.600 ng/mL	—
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 15: Cycle 1	31.363 ng/mL	Standard Deviation 25.923
Dose Escalation Stage: HMPL-689 15 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 13	18.800 ng/mL	—
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 13	17.300 ng/mL	—
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 3	14.390 ng/mL	Standard Deviation 11.752
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 11	35.050 ng/mL	Standard Deviation 30.193
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 5	18.150 ng/mL	Standard Deviation 11.102
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 9	18.533 ng/mL	Standard Deviation 10.883
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 15: Cycle 1	16.667 ng/mL	Standard Deviation 16.22
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 7	22.850 ng/mL	Standard Deviation 13.647
Dose Escalation Stage: HMPL-689 20 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 2	15.237 ng/mL	Standard Deviation 5.614
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 3	43.800 ng/mL	Standard Deviation 13.444
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 15: Cycle 1	132.125 ng/mL	Standard Deviation 165.321
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 2	46.325 ng/mL	Standard Deviation 16.555
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 5	25.167 ng/mL	Standard Deviation 25.877
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 7	75.967 ng/mL	Standard Deviation 54.444
Dose Escalation Stage: HMPL-689 25 mg QD	Dose Expansion Stage: Plasma Trough Concentration of HMPL-689	Day 1: Cycle 9	28.950 ng/mL	Standard Deviation 4.596

Source: ClinicalTrials.gov · Data processed: Feb 17, 2026

Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas

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Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)

Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)

Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events

Dose Escalation and Dose Expansion Stages: Change From Baseline in Corrected QT Interval (QTc) Using Fridericia Formula (QTcF)

Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)

Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)

Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)

Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)

Dose Escalation and Dose Expansion Stages: Time to Response (TTR)

Dose Escalation Stage: Plasma Concentration of HMPL-689

Dose Escalation Stage: Plasma Trough Concentration (Ctrough) of HMPL-689

Dose Expansion Stage: Plasma Concentration of HMPL-689

Dose Expansion Stage: Plasma Trough Concentration of HMPL-689