IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas
- Conditions
- B-cell Non-Hodgkin LymphomaDiffuse Large B Cell LymphomaB-cell LymphomaFollicular LymphomaMantle Cell Lymphoma
- Registration Number
- NCT05365659
- Lead Sponsor
- Iksuda Therapeutics Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 140
Inclusion Criteria:<br><br> 1. Males or females, = 18 years of age<br><br> 2. Part 1: documented B cell NHL (any subtype except Burkitt lymphoma, Waldenström<br> macroglobulinemia, chronic lymphocytic leukemia); previously confirmed CD19-positive<br> if feasible<br><br> 3. Part 2: documented B cell NHL (subtypes to be determined); confirmed CD19-positive;<br> possible expansion cohorts may include:<br><br> 1. Diffuse large B cell lymphoma (including germinal center B cell type, activated<br> B cell type)<br><br> 2. Follicular lymphoma (including duodenal-type follicular lymphoma)<br><br> 3. Mantle cell lymphoma<br><br> 4. B cell lymphomas not specified<br><br> 4. If B cell NHL subtype likely to have bone marrow involvement must be willing to<br> undergo bone marrow biopsy in the event of an on-study complete response to confirm<br> response<br><br> 5. NHL that is relapsed, refractory to, or intolerant of existing therapy(ies) with<br> known curative potential, or for which no standard therapy is available; must have<br> received at least 2 prior lines of systemic therapy<br><br> 6. Must be in need of systemic treatment and not require immediate cytoreductive<br> therapy<br><br> 7. Part 1: measurable or non-measurable disease<br><br> 8. Part 2: measurable disease according to The Revised Criteria/Lugano Classification<br><br> 9. Part 1: screening tumor biopsy requested, but optional; Part 2: patient must agree<br> to screening tumor biopsy<br><br> 10. ECOG performance status 0 or 1; anticipated life expectancy = 10 weeks<br><br> 11. Women of childbearing potential and fertile men agreeing to use two effective<br> methods of contraception (including a highly effective method of contraception);<br> women beginning 2 weeks prior to the first dose, men beginning prior to the first<br> dose, and both continuing until 8 months after the last dose of study drug; male<br> patients must also agree to refrain from sperm donation during this period.<br><br> 12. Ability to understand and give written informed consent<br><br>Exclusion Criteria:<br><br> 1. Women who are pregnant or intending to become pregnant before, during, or within 8<br> months after the last dose of study drug; women who are breastfeeding<br><br> 2. Patients documented to be CD19-negative<br><br> 3. Central nervous system (CNS) lymphoma, leptomeningeal infiltration, or spinal cord<br> compression not controlled by prior surgery or radiotherapy; symptoms suggesting CNS<br> involvement<br><br> 4. Part 2: History of another malignancy within 2 years, with the exception of:<br><br> 1. Treated, non-melanoma skin cancers<br><br> 2. Treated carcinoma in situ (e.g., breast, cervix)<br><br> 3. Controlled, superficial carcinoma of the urinary bladder<br><br> 4. T1a or b prostate carcinoma treated according to standard of care, with PSA<br> within normal limits<br><br> 5. Papillary thyroid carcinoma Stage I treated surgically for cure<br><br> 5. Any of the following hematologic abnormalities at baseline (transfusion allowed > 5<br> days previous):<br><br> 1. Hemoglobin < 8.0 g/dL<br><br> 2. Absolute neutrophil count < 1,000 per mm3<br><br> 3. Platelet count < 75,000 per mm3<br><br> 6. Any of the following laboratory abnormalities at baseline:<br><br> 1. Total bilirubin > 1.5 × upper limit of normal (ULN); > 3 × ULN if with<br> Gilbert's Syndrome<br><br> 2. AST or ALT > 3 × ULN; > 5 × ULN if due to hepatic involvement by tumor<br><br> 3. Estimated GFR = 60 mL/min corrected for BSA<br><br> 4. Albuminuria defined as urine albumin to creatinine ratio < 30 mg/g or < 3<br> mg/mmol) by spot urine albumin<br><br> 7. Any of the following coagulation parameter abnormalities at baseline unless on a<br> stable dose of anticoagulant therapy for a prior thrombotic event:<br><br> 1. PT or INR > 1.5 × ULN; > 3× ULN if anticoagulated)<br><br> 2. PTT > 1.5 × ULN; > 3× ULN if anticoagulated<br><br> 8. Any of the following laboratory abnormalities at baseline aimed at assessing renal<br> function:<br><br> 1. Estimated glomerular filtration rate (eGFR) = 60 mL/min, corrected for BSA.<br><br> 2. Albuminuria defined as urine albumin to creatinine ratio (UACR) = 30 mg/g or =<br> 3 mg/mmol by spot urine albumin<br><br> 9. Patients with:<br><br> 1. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism,<br> within 4 weeks unless adequately treated and stable<br><br> 2. Active uncontrolled bleeding or a known bleeding diathesis<br><br> 10. Significant cardiovascular disease or condition, including:<br><br> 1. Congestive heart failure or angina pectoris requiring therapy<br><br> 2. Ventricular arrhythmia requiring therapy or other uncontrolled arrhythmia<br><br> 3. Severe conduction disturbance (e.g., 3rd degree heart block)<br><br> 4. QTc interval = 480 milliseconds<br><br> 5. Left ventricular ejection fraction below the lower limit of normal or < 50% by<br> MUGA scan or echocardiogram<br><br> 6. Class III or IV cardiovascular disease according to the New York Heart<br> Association Functional Classification<br><br> 7. History of acute coronary syndromes (e.g., MI, unstable angina), coronary<br> angioplasty, stenting, or bypass within 6 months<br><br> 11. Significant liver disease, including:<br><br> 1. Non-infectious hepatitis<br><br> 2. Hepatic cirrhosis (Child-Pugh Class B and Class C)<br><br> 12. Significant pulmonary disease or condition, including:<br><br> 1. Significant symptomatic COPD, as assessed by the Investigator<br><br> 2. History or any current evidence on imaging studies of interstitial lung<br> disease, pulmonary fibrosis<br><br> 3. History of pulmonary inflammatory disease, pneumonitis, ARDS<br><br> 4. History of pneumonia within 6 months<br><br> 13. Significant corneal disease or condition, including history of or current evidence<br> of keratitis<br><br> 14. Clinically significant CNS disease or condition including PML, epilepsy, vasculitis,<br> or neurodegenerative disease. Also including TIA or stroke within 6 months<br><br> 15. Known HIV infection or AIDS<br><br> 16. Active hepatitis B virus or hepatitis C virus infection<br><br> 17. Any other serious/active/uncontrolled infection, any infection requiring parenteral<br> antibiotics, or unexplained fever > 38ºC within 2 weeks<br><br> 18. Autoimmune disease or condition requiring systemic steroids or other<br> immunosuppressive medications<br><br> 19. Unresolved Grade > 1 AE associated with any prior antineoplastic therapy (except<br> persistent Grade 2 alopecia, peripheral neuropathy, decreased hemoglobin,<br> neutropenia, lymphopenia, hypomagnesemia, and/or endocrine end-organ failure being<br> adequately managed by HRT)<br><br> 20. Known or suspected hypersensitivity to any of the excipients of formulated study<br> drug<br><br> 21. Inadequate recovery from a surgical procedure, or a major surgical procedure within<br> 4 weeks<br><br> 22. Any other serious, life-threatening, or unstable preexisting medical condition,<br> including significant organ system dysfunction, or clinically significant laboratory<br> abnormality(ies)<br><br> 23. A psychiatric disorder or altered mental status that would preclude understanding of<br> the informed consent process<br><br>Drugs and Other Treatments to be Excluded:<br><br> 1. Receipt of:<br><br> 1. Any CD19-targeted therapy within 3 months<br><br> 2. Any tumor vacc
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Recommended Dose for Expansion (Part 1);Objective Response Rate (Part 2)
- Secondary Outcome Measures
Name Time Method Evaluation of the immunogenicity of IKS03 (Part 1 and 2);Plasma Concentrations of IKS03 (Part 1 and 2);Determine recommended Phase 2 dose (RP2D) (Part 2)