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

Phase 1

Conditions: Multiple Myeloma
MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-004124-10-ES

Lead Sponsor: Janssen-Cilag International NV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 80

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
-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
For a full list of inclusion criteria, please refer to the protocol, pg 60-78.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

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
a.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).

For a full list of exclusion criteria, please refer to the protocol, pg 63-81.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the overall minimal residual disease (MRD) negative rate of subjects who receive JNJ-68284528;Secondary Objective: -To evaluate the efficacy of JNJ-68284528<br>-To further characterize MRD negativity<br>-To characterize the safety of JNJ-68284528<br>-To characterize the pharmacokinetics and pharmacodynamics of JNJ-68284528<br>-To assess the immunogenicity of JNJ-68284528;Primary end point(s): MRD negative rate at a 10-5 threshold as defined by the International Myeloma Working Group (IMWG) criteria using next generation sequencing (NGS);Timepoint(s) of evaluation of this end point: Approximately at 1 year after the last subject for each individual cohort has received his or her initial dose of JNJ-68284528

Secondary Outcome Measures

Name	Time	Method

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