Multiple Myeloma, Smoldering Multiple Myeloma, Immunoglobulin Light-chain Amyloidosis
Conditions
Brief summary
The primary purpose of this study for Part 1 (Dose Escalation) is to identify the safe effective dose (recommended Phase 2 doses \[RP2Ds\]) and schedule for JNJ-79635322 treatment regimen in combination with daratumumab with or without lenalidomide or with pomalidomide; and for Part 2 (Dose Expansion) is to further characterize the safety and tolerability of JNJ-79635322 combination treatment regimens at selected RP2D(s).
Interventions
DRUGJNJ-79635322
JNJ-79635322 will be administered subcutaneously.
DRUGDaratumumab
Daratumumab will be administered subcutaneously.
DRUGPomalidomide
Pomalidomide will be administered orally.
DRUGLenalidomide
Lenalidomide will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for newly diagnosed multiple myeloma (NDMM) and relapsed or refractory multiple myeloma (R/R MM): * Have documented initial diagnosis of multiple myeloma according to IMWG diagnostic criteria * Meet treatment regimen-specific requirements as follows: Treatment regimen A (JNJ-79635322+daratumumab):Treatment regimens A1 and A3: Have been treated with 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and an inhibitor, immunomodulatory drug (IMiD) therapy for the treatment of multiple myeloma (MM); Treatment regimens A2 and A4: Newly diagnosed MM naïve to multiple myeloma (or other related plasma cell neoplasm)-directed treatments; Treatment regimen B (JNJ-79635322+pomalidomide): Have received greater than or equal to (\>=) 1 prior line of therapy, including a PI and lenalidomide, and are lenalidomide refractory OR \>=2 prior lines of therapy, including a PI and lenalidomide; Treatment Regimens C, D, and E: Newly diagnosed MM naïve to multiple myeloma (or other related plasma cell neoplasm)-directed treatments * Have a weight \>=40 kilograms * Must have an Eastern Cooperative Oncology Group status of 0 or 2 * Have measurable disease at screening as defined by at least 1 of the following: a) Serum monoclonal protein (M-protein) level \>= 0.5 gram per deciliter (g/dL); or b) Urine M-protein level \>=200 milligram (mg)/24 hours; or c) Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) \>= 10 mg/dL and abnormal serum Ig kappa lambda FLC ratio. d) For participants without measurable disease in the serum, urine, or involved FLC: presence of 1 or more focus of extramedullary disease which meets the following criteria: extramedullary plasmacytoma not contiguous with a bone lesion, at least 1 lesion \>=2 centimeter (cm) (at its greatest dimension) diameter on whole body positron emission tomography-computed tomography (or whole-body magnetic resonance imaging approved by sponsor), and not previously radiated Inclusion criteria for newly diagnosed amyloid light chain (ND AL) Amyloidosis * Have a histopathological diagnosis of amyloidosis * Have an ECOG performance status of 0 to 1 Inclusion criteria for High-risk smoldering multiple myeloma (SMM) * Have a diagnosis of SMM (per IMWG criteria) for less than or equal to (\<=) 5 years with measurable disease at the time of enrollment as defined in the protocol * Have an ECOG performance status of 0 to 1
Exclusion criteria
for NDMM and R/R MM: * Prior antitumor therapy as follows, in the specified time frame prior to the first dose of study treatment: a) Targeted therapy, epigenetic therapy, monoclonal antibody (mAb) treatment, or treatment with an investigational drug or an invasive investigational medical device within 21 days or 5 half-lives, whichever is less. b) Gene-modified adoptive cell therapy (example, chimeric antigen receptor \[CAR\] modified T cells, natural killer cells) within 90 days. c) Prior anti-CD38 directed therapy within 90 days (for treatment regimens A, C, D and E only; within 21 days for treatment regimen B). d) Conventional chemotherapy within 21 days. e) PI therapy within 14 days. f) Immunomodulatory agent therapy within 7 days. g) Radiotherapy within 14 days * Stem cell transplantation: a) Allogeneic stem cell transplant within 6 months before the first dose of study treatment. b) Received an autologous stem cell transplant \<=12 weeks before the first dose of study treatment * Nonhematologic toxicity from prior anticancer therapy that has not resolved to baseline level or to grade \<=1 (except alopecia, tissue post-RT fibrosis \[any grade\] or peripheral neuropathy grade \<=3) * Prior treatment with CD3-redirecting therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants with Dose-limiting Toxicity (DLT) | Up to 28 days | DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. |
| Number of Participants with Adverse Events (AEs) by Severity | Up to 3 Years and 3 months | An AE is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event. |
| Number of Participants with Clinically Significant Laboratory Abnormalities | Up to 3 Years and 3 months | Participants with clinically significant laboratory abnormalities (hematology and chemistry) will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Response Rate | Up to 3 Years and 3 months | Overall response rate is defined as percentage of participants with newly diagnosed multiple myeloma (NDMM), relapsed or refractory multiple myeloma (R/R MM), or high-risk smoldering multiple myeloma (SMM) who have a partial response (PR) or better evaluated by the investigator as per international myeloma working group (IMWG) 2016 criteria. |
| Percentage of Participants With Very Good Partial Response (VGPR) or Better Response Rate | Up to 3 Years and 3 months | VGPR or better response rate is defined as the percentage of participants with NDMM, R/R MM, or high-risk SMM who achieve a VGPR or better response (stringent complete response \[sCR\]+ complete response \[CR\]+VGPR) according to the IMWG 2016 criteria. |
| Percentage of Participants With CR or Better Response Rate | Up to 3 Years and 3 months | CR or better response rate is defined as the percentage of participants with NDMM R/R MM, or high-risk SMM who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria. |
| Percentage of Participants With sCR or Better Response Rate | Up to 3 Years and 3 months | sCR rate is defined as the percentage of participants with NDMM R/R MM, or high-risk SMM who achieve an sCR according to the IMWG 2016 criteria. |
| Duration of Response (DOR) | Up to 3 Years and 3 months | DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), as per IMWG 2016 response criteria, or death due to progression, whichever occurs first in participants with NDMM, R/R MM, or high-risk SMM. |
| Time to Response (TTR) | Up to 3 Years and 3 months | TTR is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participants with NDMM, R/R MM, or high-risk SMM has met all criteria for PR or better as defined by IMWG 2016 response criteria. |
| Percentage of Participants With Hematologic Response As Defined by International Amyloidosis Consensus Criteria | Up to 3 Years and 3 months | Hematologic response is defined as percentage of participants with newly diagnosed amyloid light chain (ND AL) amyloidosis who achieve complete response, very good partial response, partial response, no response and progression as defined by International amyloidosis consensus criteria present in the protocol will be reported. |
| DOR as Defined by International Amyloidosis Consensus Criteria | Up to 3 Years and 3 months | DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), as per International amyloidosis consensus criteria, or death due to progression, whichever occurs first in participants with ND AL amyloidosis. |
| TTR as Defined by International Amyloidosis Consensus Criteria | Up to 3 Years and 3 months | TTR is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participant with ND AL amyloidosis has met all criteria for PR or better as defined by International amyloidosis consensus criteria. |
| Serum Concentration of JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | Serum samples will be analyzed to determine concentrations of JNJ-79635322 and daratumumab. |
| Area Under the Serum Concentration Time Curve from Time Zero to Infinity (AUCinf) for JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | AUCinf for JNJ-79635322 and daratumumab will be reported. |
| Area Under the Serum Concentration Time Curve from Time Zero to the Last Measurable Concentration [AUC(0-t)] for JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | AUC(0-t) for JNJ-79635322 and daratumumab will be reported. |
| Area Under the Serum Concentration Time Curve During the Dosing Interval (AUCtau) for JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | AUCtau for JNJ-79635322 and daratumumab will be reported. |
| Maximum Serum Concentration (Cmax) for JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | Cmax for JNJ-79635322 and daratumumab will be reported. |
| Half Life (T1/2) for JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | T1/2 for JNJ-79635322 and daratumumab will be reported. |
| Time to Reach Cmax (Tmax) for JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | Tmax for JNJ-79635322 and daratumumab will be reported. |
| Systemic Clearance (CL/F) for JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | CL/F for JNJ-79635322 and daratumumab will be reported. |
| Apparent Volume of Distribution at Steady State (Vss/F) for JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | Vss/F for JNJ-79635322 and daratumumab will be reported. |
| Number of Participants with Presence of Anti-Drug Antibodies to JNJ-79635322 and Daratumumab | Up to 3 Years and 3 months | Participants with anti-drug antibodies to JNJ-79635322 and daratumumab will be reported. |
Countries
Australia, Israel, Netherlands, Spain, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed