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

HUTCHMED

Status and phase: Active, not recruiting; Phase 1

Conditions: Lymphoma

Treatments: Drug: HMPL-689

Study type: Interventional

Funder types: Industry

Identifiers

NCT03786926

2018-689-00US1

Details and patient eligibility

About

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

Full 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.

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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53 participants in 1 patient group

Treatment

Experimental group

Description:

All patients take HMPL-689 taken daily

Treatment:

Drug: HMPL-689