IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas

A Phase 1 Cohort Dose Escalation and Expansion Trial to Determine the Safety, Tolerance, Maximum Tolerated Dose, and Preliminary Antineoplastic Activity of IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas (NHL)

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 Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; B-cell Lymphoma; Mantle Cell Lymphoma; Diffuse Large B Cell Lymphoma; B-cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: IKS03

Detailed Description

The study will consist of 2 parts: dose-escalation (Part I) and dose-expansion (Part II). The dose-escalation part (Part I) of the study is to evaluate the safety and tolerability of increasing dose levels of IKS03 to establish a recommended Phase 2 dose (RP2D); and the dose-expansion part (Part II) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of IKS03 at the RP2D.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David Browning; Phone Number: 615-975-7776; Email: david.browning@iksuda.com

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
      • Principal Investigator: Amanda Johnston, MD
  • South Australia
    • Adelaide, South Australia, Australia
      • Recruiting
      • Royal Adelaide Hospital
      • Contact: Pratyush Giri, MBBS
      • Principal Investigator: Pratyush Giri, MBBS
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Recruiting
      • Royal Hobart Hospital
      • Principal Investigator: Rosemary Harrup, MD
  • Western Australia
    • Perth, Western Australia, Australia
      • Recruiting
      • Linear Clinical Research
      • Contact: Katharine Lewis, MD
      • Principal Investigator: Katharine Lewis, MD
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital
      • Principal Investigator: Sarit Assouline, MD
      • Contact: Sarit Assouline, MD
• Italy
  • Candiolo, Italy
    • Recruiting
    • Istituto Nazionale Oncologico Candiolo
    • Contact: Umberto Vitolo, M.D.
    • Principal Investigator: Umberto Vitolo, M.D.
  • Milan, Italy
    • Recruiting
    • Istituto Europeo di Oncologia
    • Contact: Enrico Derenzini, M.D.
    • Principal Investigator: Enrico Derenzini, M.D.
  • Milan, Italy
    • Recruiting
    • Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
    • Contact: Andres Jose Maria Ferreri, M.D.
    • Principal Investigator: Andres Jose Maria Ferreri, M.D.
  • Milan, Italy
    • Recruiting
    • Istituto Europeo Clinico Humanitas
    • Contact: Carmelo Carlo-Stella, M.D.
    • Principal Investigator: Carmelo Carlo-Stella, M.D.
• Spain
  • Badalona, Spain
    • Recruiting
    • Institut Catala D'oncologia
    • Contact: Mireia Franch-Sarto, M.D.
    • Principal Investigator: Mireia Franch-Sarto, M.D.
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Quironsalud Madrid
    • Contact: Maria del Carmen Martinez-Chamorro, M.D.
    • Principal Investigator: Maria del Carmen Martinez-Chamorro, M.D.
  • Salamanca, Spain
    • Recruiting
    • Hospital Clinico Universitario de Salamanca
    • Contact: Alejandro Martin Garcia-Sancho, M.D.
    • Principal Investigator: Alejandro Martin Garcia-Sancho, M.D.
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Withdrawn
      • University of Maryland Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females, ≥ 18 years of age
2. Part I: documented B cell NHL (any subtype except Burkitt lymphoma, Waldenström macroglobulinemia, chronic lymphocytic leukemia); previously confirmed CD19-positive if feasible

3. Part II: 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
4. 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
5. 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
6. Must be in need of systemic treatment and not require immediate cytoreductive therapy
7. Part I: measurable or non-measurable disease
8. Part II: measurable disease according to The Revised Criteria/Lugano Classification
9. Part I: screening tumor biopsy requested, but optional; Part 2: patient must agree to screening tumor biopsy
10. ECOG performance status 0 or 1
11. 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.
12. 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:

   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

5. 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

6. 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

7. 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

8. 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) ≥ 45 mg/g or ≥ 4.5 mg/mmol by spot urine albumin

9. 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

10. 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

11. Significant liver disease, including:

    1. Non-infectious hepatitis
    2. Hepatic cirrhosis (Child-Pugh Class B and Class C)

12. 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 1 month
13. Significant corneal disease or condition, including history of or current evidence of keratitis
14. Clinically significant CNS disease or condition including PML, epilepsy, vasculitis, or neurodegenerative disease. Also including TIA or stroke within 6 months
15. Known HIV infection or AIDS
16. Active hepatitis B virus or hepatitis C virus infection
17. Any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks
18. Autoimmune disease or condition requiring systemic steroids or other immunosuppressive medications
19. 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)
20. Known or suspected hypersensitivity to any of the excipients of formulated study drug
21. Inadequate recovery from a surgical procedure, or a major surgical procedure within 4 weeks
22. Any other serious, life-threatening, or unstable preexisting medical condition, including significant organ system dysfunction, or clinically significant laboratory abnormality(ies)
23. A psychiatric disorder or altered mental status that would preclude understanding of the informed consent process

Drugs and Other Treatments to be Excluded:

1. Receipt of:

   1. Any CD19-targeted therapy within 4 weeks
   2. Any tumor vaccine within 6 weeks (must have progressed if previously received)
2. Prior autologous/allogeneic CAR-T therapy if known to be CD19-negative after
3. Any other antineoplastic agent for the primary malignancy without delayed toxicity within 3 weeks or 5 plasma half-lives, whichever is shortest (except nitrosoureas and mitomycin C within 6 weeks)
4. Any other investigational treatments within 3 weeks

5. Drugs known to impair renal function, including:

   1. NSAIDS within 3 days
   2. Aminoglycoside antibiotics, amphotericin B, etc. within 1 week
   3. Bisphosphonates within 1 month
6. Prior solid organ transplant

7. Allogeneic HSCT within 6 months, or:

   1. If receiving immunosuppression
   2. If with active evidence of GVHD
8. Autologous hematopoietic stem cell transplantation (HSCT) within 3 months

9. Radiotherapy:

   1. To target lesions within 4 weeks unless progression of the lesion has been documented
   2. To non-target lesions within 1 week
10. Live/live-attenuated vaccines against infectious diseases within 4 weeks
11. Immunosuppressive or systemic glucocorticoid therapy (> 10 mg prednisone daily or equivalent) within 2 weeks
12. Prophylactic use of hematopoietic growth factors within 1 week
13. Herbal therapies and supplements within 2 weeks
14. Strong inhibitors of cytochrome P450 within 2 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

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 criterion 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 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; 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 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; 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 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; 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 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; 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 Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (Part I)	RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data	Up to 20 months
Objective Response Rate (Part II)	Antineoplastic effects will be assessed by Criteria for Response Assessment: The Lugano Classification (Cheson 2014)	up to 42 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Iksuda Therapeutics Ltd.
• Investigators: Study Director: Debra Wood, MD, Iksuda Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: May 2, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (Actual): May 9, 2022

Study Record Updates

• Last Update Posted (Actual): July 29, 2026
• Last Update Submitted That Met QC Criteria: July 27, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: lymphoma; DLBCL; NHL; non-Hodgkin lymphoma; MCL; CD19; advance lymphoma; IKS03
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell
• Other Study ID Numbers: IKS03-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No