IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas
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ClinicalTrials.gov Identifier: NCT05365659 |
Recruitment Status :
Recruiting
First Posted : May 9, 2022
Last Update Posted : October 3, 2023
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Condition or disease | Intervention/treatment | Phase |
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B-cell Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma Follicular Lymphoma Mantle Cell Lymphoma B-cell Lymphoma | Drug: IKS03 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 140 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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) |
Actual Study Start Date : | September 5, 2023 |
Estimated Primary Completion Date : | September 2025 |
Estimated Study Completion Date : | September 2027 |
Arm | Intervention/treatment |
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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.
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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. |
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.
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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. |
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. |
- 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)
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05365659
Contact: David Browning | +1-615-975-7776 | david.browning@iksuda.com |
United States, Maryland | |
University of Maryland Baltimore | Recruiting |
Baltimore, Maryland, United States, 21201 | |
Contact: Seung Lee, MD | |
Principal Investigator: Seung Lee, MD | |
Australia, Western Australia | |
Linear Clinical Research | Recruiting |
Perth, Western Australia, Australia | |
Contact: Katharine Lewis, MD | |
Principal Investigator: Katharine Lewis, MD | |
Canada, Quebec | |
Jewish General Hospital | Recruiting |
Montréal, Quebec, Canada, H3T 1E2 | |
Contact: Sarit Assouline, MD | |
Principal Investigator: Sarit Assouline, MD |
Study Director: | Paul I Nadler, MD | Iksuda Therapeutics |
Responsible Party: | Iksuda Therapeutics Ltd. |
ClinicalTrials.gov Identifier: | NCT05365659 |
Other Study ID Numbers: |
IKS03-01 |
First Posted: | May 9, 2022 Key Record Dates |
Last Update Posted: | October 3, 2023 |
Last Verified: | September 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
CD19 non-Hodgkin lymphoma NHL DLBCL |
MCL advance lymphoma IKS03 lymphoma |
Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Mantle-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type |
Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |