An Open Label Study of JNJ-68284528, Directed Against BCMA in Subjects with Multiple Myeloma

Phase 1

• Conditions: Multiple Myeloma; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-506587-13-00
• Lead Sponsor: Janssen - Cilag International

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-01-31
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

Cohort A: -1-3 prior lines of therapy, including PI and IMiD -Lenalidomide refractory -Anti-CD38 mAb exposure not required -PD per IMWG criteria =6 months of last regimen; confirmation may be either central or local -Prior SCT allowed (allo: >6 months before apheresis; auto: >12 weeks before apheresis), Cohort B: -Frontline therapy with PI and IMiD -Transplant and non-transplant patients -Anti-CD38 mAb exposure not required -PD per IMWG criteria =12 months of: a. Autologous SCT b. Start of initial therapy (non-transplanted patients), Cohort C: -Previously treated with PI, IMiD, anti-CD38 mAb and BCMA-directed therapy (as monotherapy or in combination) a. Irrespective of dose level or response to prior BCMA-directed therapy -PD per IMWG criteria a. =12 months of last line of therapy b. =6 months of prior therapy, and refractory or non-responsive to their most recent line of therapy, Cohort A, B, C: Measurable disease at Screening as defined by any of the following: -Serum M-protein =1.0 g/dL or urine M-protein level =200 mg/24 hours; or -Light chain MM without measurable disease in serum or urine: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio -Central screening lab results required for all study patients: Local laboratory assessments may be used to establish measurable disease at Screening, with local laboratory result =125% of requirements -For subjects with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria. -Lab values as defined in the protocol, Cohort D: -Newly diagnosed MM per IMWG with 4 to 8 total cycles of initial therapy, including induction, high-dose therapy and ASCT with or without consolidation a. Previously treated for smoldering myeloma not eligible b. Patient treated with consolidation must have received =2 cycles - Received IMiD or PI or both in combination with steroid as part of induction or consolidation regimen -Tx with alkylating therapy (eg, cyclophosphamide) or mAb during induction/ consolidation permitted -Labs as specified in the protocol -women of childbearing potential must follow the contraception criteria outlined in the local global REVLIMID® pregnancy prevention program or equivalent local Risk Evaluation and Mitigation Strategy (REMS), whichever is more stringent, as applicable in their region. -Men should agree to practice contraception according to and for the time frame specified in the local global REVLIMID® pregnancy prevention program or equivalent local REMS, whichever is more stringent, as applicable in their region., Cohort E: -Measurable disease at Screening - Documented diagnosis of MM according to IMWG criteria -Labs as specified in the protocol, Cohort F: - Documented new diagnosis of multiple myeloma according to IMWG diagnostic criteria. - Multiple myeloma classified as standard risk per International Staging System (ISS) stage I or II disease criteria - Received initial therapy as specified in protocol. Acceptable combinations include: a. daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd) or b. daratumumab, lenalidomide and dexamethasone (D-Rd) or c. a carfilzomib-based triplet or quadruplet regimen - Patient must have a documented efficacy response of VGPR or better, without Progressive Disease prior to enrollment, as assessed per IMWG 2016 criteri

Exclusion Criteria

Key Exclusion criteria (All cohorts): -Antitumor treatment washout prior to apheresis -Toxicity from previous anticancer therapy must have resolved to baseline or =Grade 1 except alopecia or peripheral neuropathy - Serious underlying medical condition, eg: a.Clinically significant cardiac conditions (CHF, MI, LVEF <45%) b. Active / Hx of autoimmune disease within 3 yrs c. Dementia or altered mental status d. Serious viral, bacterial or uncontrolled systemic fungal infection e. Seropositive for HIV f. Clinically significant Hepatitis B or C infection - Cumulative dose of corticosteroids equivalent to =70 mg of prednisone =7 days prior to apheresis - Stroke or seizure =6 months - Pregnant, breast-feeding or planning to become pregnant / father child while enrolled in study and until 1 year after receiving a JNJ-68284528 infusion - Contraindications, known life threatening allergies, hypersensitivity, or intolerance to cyclophosphamide, fludarabine, or JNJ-68284528 or its excipients, including DMSO (refer to Investigator's Brochure)., Cohort D: -Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study and until 1 year after receiving a JNJ-68284528 infusion or for 4 weeks following discontinuation of lenalidomide (whichever is later). -Contraindications, known life threatening allergies, hypersensitivity, or intolerance to cyclophosphamide, fludarabine, lenalidomide, or JNJ68284528 or its excipients, including DMSO (refer to Investigator's Brochure)., Cohort E: Contraindications, known life threatening allergies, hypersensitivity, or intolerance to boron or mannitol, hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies or human proteins, cyclophosphamide, fludarabine, lenalidomide, daratumumab, bortezomib, dexamethasone, or JNJ-68284528 excipients, including DMSO. -Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study and until: 1 year after receiving a JNJ-68284528 infusion, or for 4 weeks following discontinuation of lenalidomide, or until 3 months after daratumumab (whichever is later). -Plans to father a child while enrolled in this study until: 1 year after receiving a JNJ-68284528 infusion, or for 4 weeks following discontinuation of lenalidomide, or until 3 months after daratumumab (whichever is later)., Cohort F: - Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. - Prior therapy, prior to apheresis - Received a cumulative dose of corticosteroids equivalent to =70 mg of prednisone within the 7 days prior to apheresis - Ongoing toxicity from previous anticancer therapy must have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy. - Major surgery within 2 weeks prior to apheresis, or surgery planned after apheresis up to 2 weeks after cilta-cel administration. For a full list of exclusion criteria, please refer to the protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified