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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).

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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.

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Eligibility criteria

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

Inclusion criteria

Males or females, ≥ 18 years of age

Part 1: documented B cell NHL (any subtype except Burkitt lymphoma, Waldenström macroglobulinemia, chronic lymphocytic leukemia); previously confirmed CD19-positive if feasible

Part 2: documented B cell NHL (subtypes to be determined); confirmed CD19-positive; possible expansion cohorts may include: 1. Diffuse large B cell lymphoma (including germinal center B cell type, activated B cell type) 2. Follicular lymphoma (including duodenal-type follicular lymphoma) 3. Mantle cell lymphoma 4. B cell lymphomas not specified

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

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

Must be in need of systemic treatment and not require immediate cytoreductive therapy

Part 1: measurable or non-measurable disease

Part 2: measurable disease according to The Revised Criteria/Lugano Classification

Part 1: screening tumor biopsy requested, but optional; Part 2: patient must agree to screening tumor biopsy

ECOG performance status 0 or 1; anticipated life expectancy ≥ 10 weeks

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.

Ability to understand and give written informed consent

Exclusion criteria

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

Patients documented to be CD19-negative

Central nervous system (CNS) lymphoma, leptomeningeal infiltration, or spinal cord compression not controlled by prior surgery or radiotherapy; symptoms suggesting CNS involvement

Part 2: History of another malignancy within 2 years, with the exception of: 1. Treated, non-melanoma skin cancers 2. Treated carcinoma in situ (e.g., breast, cervix) 3. Controlled, superficial carcinoma of the urinary bladder 4. T1a or b prostate carcinoma treated according to standard of care, with PSA within normal limits 5. Papillary thyroid carcinoma Stage I treated surgically for cure

Any of the following hematologic abnormalities at baseline (transfusion allowed > 5 days previous): 1. Hemoglobin < 8.0 g/dL 2. Absolute neutrophil count < 1,000 per mm3 3. Platelet count < 75,000 per mm3

Any of the following laboratory abnormalities at baseline: 1. Total bilirubin > 1.5 × upper limit of normal (ULN); > 3 × ULN if with Gilbert's Syndrome 2. AST or ALT > 3 × ULN; > 5 × ULN if due to hepatic involvement by tumor 3. Estimated GFR ≤ 60 mL/min corrected for BSA 4. Albuminuria defined as urine albumin to creatinine ratio < 30 mg/g or < 3 mg/mmol) by spot urine albumin

Any of the following coagulation parameter abnormalities at baseline unless on a stable dose of anticoagulant therapy for a prior thrombotic event: 1. PT or INR > 1.5 × ULN; > 3× ULN if anticoagulated) 2. PTT > 1.5 × ULN; > 3× ULN if anticoagulated

Any of the following laboratory abnormalities at baseline aimed at assessing renal function: 1. Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min, corrected for BSA. 2. Albuminuria defined as urine albumin to creatinine ratio (UACR) ≥ 30 mg/g or ≥ 3 mg/mmol by spot urine albumin

Patients with: 1. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks unless adequately treated and stable 2. Active uncontrolled bleeding or a known bleeding diathesis

Significant cardiovascular disease or condition, including: 1. Congestive heart failure or angina pectoris requiring therapy 2. Ventricular arrhythmia requiring therapy or other uncontrolled arrhythmia 3. Severe conduction disturbance (e.g., 3rd degree heart block) 4. QTc interval ≥ 480 milliseconds 5. Left ventricular ejection fraction below the lower limit of normal or < 50% by MUGA scan or echocardiogram 6. Class III or IV cardiovascular disease according to the New York Heart Association Functional Classification 7. History of acute coronary syndromes (e.g., MI, unstable angina), coronary angioplasty, stenting, or bypass within 6 months

Significant liver disease, including: 1. Non-infectious hepatitis 2. Hepatic cirrhosis (Child-Pugh Class B and Class C)

Significant pulmonary disease or condition, including: 1. Significant symptomatic COPD, as assessed by the Investigator 2. History or any current evidence on imaging studies of interstitial lung disease, pulmonary fibrosis 3. History of pulmonary inflammatory disease, pneumonitis, ARDS 4. History of pneumonia within 6 months

Significant corneal disease or condition, including history of or current evidence of keratitis

Clinically significant CNS disease or condition including PML, epilepsy, vasculitis, or neurodegenerative disease. Also including TIA or stroke within 6 months

Known HIV infection or AIDS

Active hepatitis B virus or hepatitis C virus infection

Any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks

Autoimmune disease or condition requiring systemic steroids or other immunosuppressive medications

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)

Known or suspected hypersensitivity to any of the excipients of formulated study drug

Inadequate recovery from a surgical procedure, or a major surgical procedure within 4 weeks

Any other serious, life-threatening, or unstable preexisting medical condition, including significant organ system dysfunction, or clinically significant laboratory abnormality(ies)

A psychiatric disorder or altered mental status that would preclude understanding of the informed consent process

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2023-09-05

Primary completion: 2025-09-01

Study completion finish: 2027-09-01

Study type

TREATMENT

Phase

PHASE1

Trial ID

NCT05365659

Intervention or treatment

DRUG: IKS03

Conditions

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

Image related to Diffuse Large B Cell Lymphoma

Condition: Diffuse Large B Cell Lymphoma, Follicular Lymphoma and more
DRUG: IKS03
Westmead, New South Wales, Australia and more
Sponsor: Iksuda Therapeutics Ltd.

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Westmead Hospital

Research sites nearby

Select from list below to view details:

Westmead Hospital
Westmead, New South Wales, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Linear Clinical Research
Perth, Western Australia, Australia

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/Arm	Intervention/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 criteria is met.	DRUG: IKS03 IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
EXPERIMENTAL: Dose Expansion: Diffuse-Large B-Cell Lymphoma Participants Each patient will receive IKS03 at the recommended dose for expansion (RDE) defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.	DRUG: IKS03 IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
EXPERIMENTAL: Dose Expansion: Follicular Cell Lymphoma Participants Each patient will receive IKS03 at the recommended dose for expansion (RDE) defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.	DRUG: IKS03 IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
EXPERIMENTAL: Dose Expansion: Mantle Cell Lymphoma Participants Each patient will receive IKS03 at the recommended dose for expansion (RDE) defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.	DRUG: IKS03 IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
EXPERIMENTAL: Dose Expansion: Other B cell lymphoma (B-NHL not otherwise specified [NOS]) Each patient will receive IKS03 at the recommended dose for expansion (RDE) defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.	DRUG: IKS03 IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Recommended Dose for Expansion (Part 1)	RDE will be determined using dose limiting toxicities (DLTs) and all other available study data	Up 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

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Evaluation of the immunogenicity of IKS03 (Part 1 and 2)	Occurrence of ADA measured in serum at selected timepoints during the study	Up to 42 months
Plasma Concentrations of IKS03 (Part 1 and 2)	Pharmacokinetic profile will be characterized by concentrations of IKS03	Up to 42 months
Determine recommended Phase 2 dose (RP2D) (Part 2)	Based on evidence of antitumor activity, acceptable tolerability, evidence of achieving target plasma concentration	Up to 42 months

Frequently Asked Questions

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References

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