A Phase 1 Study of JNJ-95804306 for Relapsed or Refractory Hematological Malignancies

Trial details

Who runs it

Janssen Cilag International

Trial code

EU 2026-525234-39-00

Record updated

2026. november 6.

Original description

Part 1 (Dose Escalation): To characterize the safety and tolerability of JNJ- 95804306 and identify putative RP2D regimen(s) in R/R AML/HR MDS and R/R CLL/SLL/NHL in monotherapy and in R/R AML/HR MDS and R/R CLL/SLL in combination therapy ; Part 2 (Dose Expansion): To further characterize the safety for JNJ-95804306 at the putative RP2D(s) in the expansion cohort(s)in R/R AML/HR MDS and R/R CLL/SLL/NHL monotherapy and in R/R AML/HR MDS and R/R CLL/SLL in combination therapyRead full original descriptionShow less

A Phase 1, First-in-human, Dose Escalation Study of JNJ-95804306 for Relapsed or Refractory Hematological Malignancies

Part 1 (Dose Escalation): To characterize the safety and tolerability of JNJ- 95804306 and identify putative RP2D regimen(s) in R/R AML/HR MDS and R/R CLL/SLL/NHL in monotherapy and in R/R AML/HR MDS and R/R CLL/SLL in combination therapy ; Part 2 (Dose Expansion): To further characterize the safety for JNJ-95804306 at the putative RP2D(s) in the expansion cohort(s)in R/R AML/HR MDS and R/R CLL/SLL/NHL monotherapy and in R/R AML/HR MDS and R/R CLL/SLL in combination therapy

Inclusion: 1.At the time of informed consent, be ≥18 years of age or the legal age to provide informed consent in the jurisdiction in which the study is taking place; Diagnosis: a.AML per ICC 2022 or MDS per WHO 2022 classified as moderate high, high, or very high-risk per the IPSS-M. If molecular results within the 12 months prior to informed consent are not available, participants must have IPSS-R >3.5, which corresponds with risk categories of intermediate, high-risk, or very high-risk MDS. (i) All participants must have relapsed or refractory disease and have exhausted or are ineligible for standard therapeutic options. Eligible participants will have a bone marrow blast burden ≥5%. Participants with newly transformed secondary AML may be enrolled at the investigator’s discretion, provided that no standard therapeutic options exist based on the treatment prior to transformation. b. CLL/SLL/NHL: All participants must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator’s judgment. c. CLL/SLL meeting 2018 iwCLL NCI Working Group Guidelines that meet the following criteria: (i.) Participants must have received at least 2 prior lines of therapy. (ii.) Have clinically measurable disease (lymphocytosis >5×10⁹/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam) OR d. B-cell NHL as defined per the 2022 WHO classification: In addition, the following subtype-specific criteria outlined below must be met: (i.) If DLBCL: Previously treated with a minimum of 2 prior lines of systemic therapy, received, or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent. (ii.) If FL/MZL (except MALT) or WM: Previously treated with a minimum of 2 prior lines of systemic therapy, with at least one prior line containing an anti-CD20 antibody. Participants with transformed FL/MZL are eligible, with eligibility based on the transformed histology and its applicable treatment paradigm. (iii.) If MCL: Previously treated with at least 1 prior line of systemic therapy containing an anti-CD20 antibody; ECOG performance status score between 0 and 2.

Exclusion: Had major surgery (eg, requiring general anesthesia) or had significant traumatic injury within 2 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study; Had any of the following within 6 months prior to start of study treatment: severe or unstable angina, myocardial infarction, major thromboembolic events (eg, pulmonary embolism, cerebrovascular accident), clinically significant ventricular arrhythmias or heart failure NYHA functional classification Class III – IV; Any of the following prior therapies: a. AML/MDS: (i.) Chemotherapy (with the exception of hydroxyurea and/or a single dose of cytarabine up to 1 g/m2 as noted above) within 2 weeks of first dose of study drug. (ii.) Local radiation within 7 days of first dose of study drug. Note: must have at least 1 measurable lesion beyond what is irradiated. (iii.) Antibody use within 2 weeks of first dose of study drug. (iv.) Targeted therapy (with the exception of a BCL2 targeting agent) or investigational agents within 2 weeks or 5 half-lives, whichever is shorter, of first dose of study drug. (v.) A BCL2 targeting agent within 2 weeks of first dose of study drug. (vi) Other targeted therapy (with the exception of a BCL2 targeting agent) or investigational agents within 2 weeks or 5 half-lives, whichever is shorter, of first dose of study drug. b. CLL: (i.) Chemotherapy or immunotherapy within 2 weeks before the first administration of study drug. (ii.) Local radiation within 7 days of first dose of study drug. (iii.) Monoclonal antibody (single target) use within 4 weeks of first dose of study drug. (iv.) A BCL2-targeting agent within 2 weeks of first dose of study drug. (v.)For other targeted therapies, inclusive of T-cell engagers, and investigational agents where the half-life is known, there should be a treatment-free window of at least 2 weeks or 5 half-lives, whichever is shorter; Have evidence of uncontrolled systemic viral, bacterial, or fungal infection. Antimicrobial prophylaxis is permitted; 1.Renal function: Have a CKD-EPIcr eGFR <60 mL/min computed with the 2021 CKD-EPI eGFRcr equation; 2.Hematology laboratory results: a.AML/MDS: leukocytes >25 × 109/L b.CLL: (i.) Hemoglobin: <8.0 g/dL, or use of transfusion or growth factors within 1 week; OR (ii.) Neutrophils: <1.0 × 103/µL (in case of documented bone marrow involvement of disease <0.75×103/µL), or use of transfusion or growth factors within 1 week; OR (iii.) Platelets: <25 × 103/µL, or use of transfusion or growth factors within 1 week or active mucosal bleeding or history of a spontaneous bleeding episode within three months of first dose of study treatment; 3.Chemistry laboratory results a. AST and ALT: >3 × ULN, unless there is documented liver involvement by disease with the exclusion threshold at >4 × ULN, OR b. Total bilirubin: >1.5 × ULN, OR bilirubin in case of known congenital nonhemolytic indirect hyperbilirubinemias such as Gilbert’s Syndrome may demonstrate isolated total bilirubin ≥1.5 × ULN with conjugated [direct] bilirubin >1.5 × ULN. Note: Gilbert’s syndrome is suggested by direct bilirubin <30% (Palmer 2020), OR c. AML participants receiving combination treatment: albumin <3.0 mg/dL; Has known active CNS involvement.

EU CTIS 2026-525234-39-00