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IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas

PHASE1RECRUITING

This first-in-human study will evaluate the recommended dose for further clinical development, safety, tolerability, antineoplastic activity, immunogenicity, pharmacokinetics and pharmacodynamics of IKS03, a CD19 targeting antibody-drug conjugate, in patients with advanced B cell non-Hodgkin lymphoma (NHL).

Study details:

The study will consist of 2 parts: dose-escalation (Part 1) and dose-expansion (Part 2). The dose-escalation part (Part 1) of the study is to evaluate the safety and tolerability of increasing dose levels of IKS03 to establish a recommended dose for expansion (RDE); and the dose-expansion part (Part 2) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of IKS03 at the RDE.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Males or females, ≥ 18 years of age
  2. Part 1: documented B cell NHL (any subtype except Burkitt lymphoma, Waldenström macroglobulinemia, chronic lymphocytic leukemia); previously confirmed CD19-positive if feasible
  3. Part 2: documented B cell NHL (subtypes to be determined); confirmed CD19-positive; possible expansion cohorts may include:
  4. Diffuse large B cell lymphoma (including germinal center B cell type, activated B cell type)
  5. Follicular lymphoma (including duodenal-type follicular lymphoma)
  6. Mantle cell lymphoma
  7. B cell lymphomas not specified
  8. If B cell NHL subtype likely to have bone marrow involvement must be willing to undergo bone marrow biopsy in the event of an on-study complete response to confirm response
  9. NHL that is relapsed, refractory to, or intolerant of existing therapy(ies) with known curative potential, or for which no standard therapy is available; must have received at least 2 prior lines of systemic therapy
  10. Must be in need of systemic treatment and not require immediate cytoreductive therapy
  11. Part 1: measurable or non-measurable disease
  12. Part 2: measurable disease according to The Revised Criteria/Lugano Classification
  13. Part 1: screening tumor biopsy requested, but optional; Part 2: patient must agree to screening tumor biopsy
  14. ECOG performance status 0 or 1; anticipated life expectancy ≥ 10 weeks
  15. Women of childbearing potential and fertile men agreeing to use two effective methods of contraception (including a highly effective method of contraception); women beginning 2 weeks prior to the first dose, men beginning prior to the first dose, and both continuing until 8 months after the last dose of study drug; male patients must also agree to refrain from sperm donation during this period.
  16. Ability to understand and give written informed consent

Exclusion criteria

  1. Women who are pregnant or intending to become pregnant before, during, or within 8 months after the last dose of study drug; women who are breastfeeding
  2. Patients documented to be CD19-negative
  3. Central nervous system (CNS) lymphoma, leptomeningeal infiltration, or spinal cord compression not controlled by prior surgery or radiotherapy; symptoms suggesting CNS involvement
  4. Part 2: History of another malignancy within 2 years, with the exception of:
  5. Treated, non-melanoma skin cancers
  6. Treated carcinoma in situ (e.g., breast, cervix)
  7. Controlled, superficial carcinoma of the urinary bladder
  8. T1a or b prostate carcinoma treated according to standard of care, with PSA within normal limits
  9. Papillary thyroid carcinoma Stage I treated surgically for cure
  10. Any of the following hematologic abnormalities at baseline (transfusion allowed > 5 days previous):
  11. Hemoglobin < 8.0 g/dL
  12. Absolute neutrophil count < 1,000 per mm3
  13. Platelet count < 75,000 per mm3
  14. Any of the following laboratory abnormalities at baseline:
  15. Total bilirubin > 1.5 × upper limit of normal (ULN); > 3 × ULN if with Gilbert's Syndrome
  16. AST or ALT > 3 × ULN; > 5 × ULN if due to hepatic involvement by tumor
  17. Estimated GFR ≤ 60 mL/min corrected for BSA
  18. Albuminuria defined as urine albumin to creatinine ratio < 30 mg/g or < 3 mg/mmol) by spot urine albumin
  19. Any of the following coagulation parameter abnormalities at baseline unless on a stable dose of anticoagulant therapy for a prior thrombotic event:
  20. PT or INR > 1.5 × ULN; > 3× ULN if anticoagulated)
  21. PTT > 1.5 × ULN; > 3× ULN if anticoagulated
  22. Any of the following laboratory abnormalities at baseline aimed at assessing renal function:
  23. Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min, corrected for BSA.
  24. Albuminuria defined as urine albumin to creatinine ratio (UACR) ≥ 30 mg/g or ≥ 3 mg/mmol by spot urine albumin
  25. Patients with:
  26. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks unless adequately treated and stable
  27. Active uncontrolled bleeding or a known bleeding diathesis
  28. Significant cardiovascular disease or condition, including:
  29. Congestive heart failure or angina pectoris requiring therapy
  30. Ventricular arrhythmia requiring therapy or other uncontrolled arrhythmia
  31. Severe conduction disturbance (e.g., 3rd degree heart block)
  32. QTc interval ≥ 480 milliseconds
  33. Left ventricular ejection fraction below the lower limit of normal or < 50% by MUGA scan or echocardiogram
  34. Class III or IV cardiovascular disease according to the New York Heart Association Functional Classification
  35. History of acute coronary syndromes (e.g., MI, unstable angina), coronary angioplasty, stenting, or bypass within 6 months
  36. Significant liver disease, including:
  37. Non-infectious hepatitis
  38. Hepatic cirrhosis (Child-Pugh Class B and Class C)
  39. Significant pulmonary disease or condition, including:
  40. Significant symptomatic COPD, as assessed by the Investigator
  41. History or any current evidence on imaging studies of interstitial lung disease, pulmonary fibrosis
  42. History of pulmonary inflammatory disease, pneumonitis, ARDS
  43. History of pneumonia within 6 months
  44. Significant corneal disease or condition, including history of or current evidence of keratitis
  45. Clinically significant CNS disease or condition including PML, epilepsy, vasculitis, or neurodegenerative disease. Also including TIA or stroke within 6 months
  46. Known HIV infection or AIDS
  47. Active hepatitis B virus or hepatitis C virus infection
  48. Any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks
  49. Autoimmune disease or condition requiring systemic steroids or other immunosuppressive medications
  50. Unresolved Grade > 1 AE associated with any prior antineoplastic therapy (except persistent Grade 2 alopecia, peripheral neuropathy, decreased hemoglobin, neutropenia, lymphopenia, hypomagnesemia, and/or endocrine end-organ failure being adequately managed by HRT)
  51. Known or suspected hypersensitivity to any of the excipients of formulated study drug
  52. Inadequate recovery from a surgical procedure, or a major surgical procedure within 4 weeks
  53. Any other serious, life-threatening, or unstable preexisting medical condition, including significant organ system dysfunction, or clinically significant laboratory abnormality(ies)
  54. A psychiatric disorder or altered mental status that would preclude understanding of the informed consent process

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1

trial

Study ID

NCT05365659

Intervention or treatment

DRUG: IKS03

Conditions

  • B-cell Non-Hodgkin Lymphoma
  • Diffuse Large B Cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • B-cell Lymphoma

  • Condition: B-cell Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma and more

  • DRUG: IKS03

  • Westmead, New South Wales, Australia and more

  • Sponsor: Iksuda Therapeutics Ltd.

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Westmead Hospital

Select from list below to view details:

  • Westmead Hospital

    Westmead, New South Wales, Australia

  • Royal Adelaide Hospital

    Adelaide, South Australia, Australia

  • Royal Hobart Hospital

    Hobart, Tasmania, Australia

  • Linear Clinical Research

    Perth, Western Australia, Australia

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Who is running the clinical trial?

ITL

Iksuda Therapeutics Ltd.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Dose Escalation Cohort (Part 1)
  • Each patient will receive repeat doses (by intravenous (IV) infusions) on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
Drug: IKS03
    EXPERIMENTAL: Dose Expansion: Diffuse-Large B-Cell Lymphoma Participants
    • Each patient will receive IKS03 at the RP2D defined in Part I on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
    Drug: IKS03
      EXPERIMENTAL: Dose Expansion: Follicular Cell Lymphoma Participants
      • Each patient will receive IKS03 at the RP2D defined in Part I on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
      Drug: IKS03
        EXPERIMENTAL: Dose Expansion: Mantle Cell Lymphoma Participants
        • Each patient will receive IKS03 at the RP2D defined in Part I on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
        Drug: IKS03
          EXPERIMENTAL: Dose Expansion: Other B cell lymphoma (B-NHL not otherwise specified [NOS])
          • Each patient will receive IKS03 at the RP2D defined in Part I on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
          Drug: IKS03

            What is the study measuring?

            Primary Outcome

            MeasureDescriptionTime Frame
            Recommended Dose for Expansion (Part 1)RDE will be determined using dose limiting toxicities (DLTs) and all other available study dataUp to 20 months
            Objective Response Rate (Part 2)Antineoplastic effects will be assessed by Criteria for Response Assessment: The Lugano Classification (Cheson 2014)up to 42 months

            Secondary Outcome

            MeasureDescriptionTime Frame
            Evaluation of the immunogenicity of IKS03 (Part 1 and 2)Occurrence of ADA measured in serum at selected timepoints during the studyUp to 42 months
            Plasma Concentrations of IKS03 (Part 1 and 2)Pharmacokinetic profile will be characterized by concentrations of IKS03Up to 42 months
            Determine recommended Phase 2 dose (RP2D) (Part 2)Based on evidence of antitumor activity, acceptable tolerability, evidence of achieving target plasma concentrationUp to 42 months
            Are you running this trial?If you're a clinic or sponsor, you can claim this study.
            Claim this trial

            References

            Clinical Trials Gov: IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas

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