IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas

What this study is about

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).

Who can join (things the study team will check)

✅ You may be able to join if…

• 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:
  • Diffuse large B cell lymphoma (including germinal center B cell type, activated B cell type)
  • Follicular lymphoma (including duodenal-type follicular lymphoma)
  • Mantle cell lymphoma
  • 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

🚫 You may not be able to join if…

• 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:
  • Treated, non-melanoma skin cancers
  • Treated carcinoma in situ (e.g., breast, cervix)
  • Controlled, superficial carcinoma of the urinary bladder
  • T1a or b prostate carcinoma treated according to standard of care, with PSA within normal limits
  • Papillary thyroid carcinoma Stage I treated surgically for cure
• Any of the following hematologic abnormalities at baseline (transfusion allowed > 5 days previous):
  • Hemoglobin < 8.0 g/dL
  • Absolute neutrophil count < 1,000 per mm3
  • Platelet count < 75,000 per mm3
• Any of the following laboratory abnormalities at baseline:
  • Total bilirubin > 1.5 × upper limit of normal (ULN); > 3 × ULN if with Gilbert's Syndrome
  • AST or ALT > 3 × ULN; > 5 × ULN if due to hepatic involvement by tumor
  • Estimated GFR ≤ 60 mL/min corrected for BSA
  • 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:
  • PT or INR > 1.5 × ULN; > 3× ULN if anticoagulated)
  • PTT > 1.5 × ULN; > 3× ULN if anticoagulated
• Any of the following laboratory abnormalities at baseline aimed at assessing renal function:
  • Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min, corrected for BSA.
  • Albuminuria defined as urine albumin to creatinine ratio (UACR) ≥ 30 mg/g or ≥ 3 mg/mmol by spot urine albumin
• Patients with:
  • Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks unless adequately treated and stable
  • Active uncontrolled bleeding or a known bleeding diathesis
• Significant cardiovascular disease or condition, including:
  • Congestive heart failure or angina pectoris requiring therapy
  • Ventricular arrhythmia requiring therapy or other uncontrolled arrhythmia
  • Severe conduction disturbance (e.g., 3rd degree heart block)
  • QTc interval ≥ 480 milliseconds
  • Left ventricular ejection fraction below the lower limit of normal or < 50% by MUGA scan or echocardiogram
  • Class III or IV cardiovascular disease according to the New York Heart Association Functional Classification
  • History of acute coronary syndromes (e.g., MI, unstable angina), coronary angioplasty, stenting, or bypass within 6 months
• Significant liver disease, including:
  • Non-infectious hepatitis
  • Hepatic cirrhosis (Child-Pugh Class B and Class C)
• Significant pulmonary disease or condition, including:
  • Significant symptomatic COPD, as assessed by the Investigator
  • History or any current evidence on imaging studies of interstitial lung disease, pulmonary fibrosis
  • History of pulmonary inflammatory disease, pneumonitis, ARDS
  • 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

+ 17 more criteria — see the full checklist in the app.

Where this trial is running

• University of Maryland Baltimore, Baltimore, Maryland, United States
• 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
• Jewish General Hospital, Montreal, Quebec, Canada
• La Fondazione e l'Istituto di Candiolo, Candiolo, Italy
• Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy
• Istituto Europeo Clinico Humanitas, Milan, Italy
• Istituto Europeo di Oncologia, Milan, Italy
• Institut Catala D&#39;Oncologia, Badalona, Spain
• Hospital Universitario Quironsalud Madrid, Madrid, Spain

+ 1 more sites.

Who to contact

David Browning · 615-975-7776 · david.browning@iksuda.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT05365659.