May 2, 2022
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May 9, 2022
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October 3, 2023
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September 5, 2023
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September 2025 (Final data collection date for primary outcome measure)
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- Recommended Dose for Expansion (Part 1) [ Time Frame: Up to 20 months ]
RDE will be determined using dose limiting toxicities (DLTs) and all other available study data
- Objective Response Rate (Part 2) [ Time Frame: up to 42 months ]
Antineoplastic effects will be assessed by Criteria for Response Assessment: The Lugano Classification (Cheson 2014)
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- Recommended Dose for Expansion (Part 1) [ Time Frame: Up to 20 months ]
RDE will be determined using dose limiting toxicities (DLTs) and all other available study data
- Antineoplastic effect of IKS03 (Part 2) [ Time Frame: up to 42 months ]
Antineoplastic effects will be assessed by Criteria for Response Assessment: The Lugano Classification (Cheson 2014)
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- Evaluation of the immunogenicity of IKS03 (Part 1 and 2) [ Time Frame: Up to 42 months ]
Occurrence of ADA measured in serum at selected timepoints during the study
- Plasma Concentrations of IKS03 (Part 1 and 2) [ Time Frame: Up to 42 months ]
Pharmacokinetic profile will be characterized by concentrations of IKS03
- Determine recommended Phase 2 dose (RP2D) (Part 2) [ Time Frame: Up to 42 months ]
Based on evidence of antitumor activity, acceptable tolerability, evidence of achieving target plasma concentration
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Same as current
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Not Provided
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Not Provided
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IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas
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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)
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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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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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Interventional
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Phase 1
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Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- B-cell Non-Hodgkin Lymphoma
- Diffuse Large B Cell Lymphoma
- Follicular Lymphoma
- Mantle Cell Lymphoma
- B-cell Lymphoma
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Drug: IKS03
IKS03 is a human monoclonal antibody (Ab) targeting CD19 linked to a pyrrolobenzodiazepine (PBD) pro-drug as the cytotoxic agent.
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- 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.
Intervention: Drug: IKS03
- 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.
Intervention: Drug: IKS03
- 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.
Intervention: Drug: IKS03
- 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.
Intervention: Drug: IKS03
- 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.
Intervention: Drug: IKS03
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Not Provided
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Recruiting
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140
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Same as current
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September 2027
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September 2025 (Final data collection date for primary outcome measure)
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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
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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 6 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 6 months after the last dose of study drug; women who are breastfeeding.
- Central nervous system (CNS) lymphoma, leptomeningeal infiltration, or spinal cord compression not controlled by prior surgery or radiotherapy; symptoms suggesting CNS involvement
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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
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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
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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
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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
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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
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Significant liver disease, including:
- Non-infectious hepatitis
- Hepatic cirrhosis (Child-Pugh Class C)
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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
- 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
- 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
Drugs and Other Treatments to be Excluded:
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Receipt of:
- Any CD19-targeted therapy within 3 months
- Any tumor vaccine within 6 weeks (must have progressed if previously received)
- Prior autologous/allogeneic CAR-T therapy if known to be CD19-negative after
- Any other antineoplastic agent for the primary malignancy without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest (except nitrosoureas and mitomycin C within 6 weeks)
- Any other investigational treatments within 4 weeks
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Drugs known to impair renal function, including:
- NSAIDS within 3 days
- Aminoglycoside antibiotics, amphotericin B, etc. within 1 week
- Bisphosphonates within 1 month
- Autologous hematopoietic stem cell transplantation (HSCT) within 3 months
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Allogeneic HSCT within 6 months, or:
- If receiving immunosuppression
- If with active evidence of GVHD
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Radiotherapy:
- To target lesions within 4 weeks unless progression of the lesion has been documented
- To non-target lesions within 1 week
- Live/live-attenuated vaccines against infectious diseases within 4 weeks
- Immunosuppressive or systemic glucocorticoid therapy (> 10 mg prednisone daily or equivalent) within 2 weeks
- Prophylactic use of hematopoietic growth factors within 1 week
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Australia, Canada, United States
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NCT05365659
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IKS03-01
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No
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Iksuda Therapeutics Ltd.
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Same as current
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Iksuda Therapeutics Ltd.
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Same as current
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Not Provided
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Study Director: |
Paul I Nadler, MD |
Iksuda Therapeutics |
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Iksuda Therapeutics Ltd.
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September 2023
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