Clinical trial NCT06768489: A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide or in Combination With Pomalidomide for Multiple Myeloma
Official title: A Phase 1b Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide or in Combination With Pomalidomide for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2025-01-10
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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 regimen A1: 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 regimen A2: 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

Exclusion Criteria:

* Any serious underlying medical conditions, such as: a) Evidence of active viral, bacterial, or systemic fungal infection requiring ongoing antiviral, antibacterial, or antifungal treatment. b) Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment. c) Cardiac conditions (myocardial infarction, unstable angina, or coronary artery bypass graft \<=6 months prior to enrollment; New york heart association stage III or IV congestive heart failure et cetera)
* 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 regimen A 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 less than or equal to (\<=)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
* The following medical conditions: pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation, human immunodeficiency (HIV) infection, active hepatitis B or C infection, stroke or seizure within 6 months prior to first dose of study treatment

Primary outcomes:
measure: Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: Up to 28 days
measure: Number of Participants with Adverse Events (AEs) by Severity
timeFrame: Up to 3 Years and 3 months
measure: Number of Participants with Clinically Significant Laboratory Abnormalities
timeFrame: Up to 3 Years and 3 months
Secondary outcomes:
measure: Percentage of Participants With Overall Response Rate
timeFrame: Up to 3 Years and 3 months
measure: Duration of Response (DOR)
timeFrame: Up to 3 Years and 3 months
measure: Time to Response (TTR)
timeFrame: Up to 3 Years and 3 months
measure: Serum Concentration of JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Area Under the Serum Concentration Time Curve from Time Zero to Infinity (AUCinf) for JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Area Under the Serum Concentration Time Curve from Time Zero to the Last Measurable Concentration [AUC(0-t)] for JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Area Under the Serum Concentration Time Curve During the Dosing Interval (AUCtau) for JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Maximum Serum Concentration (Cmax) for JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Half Life (T1/2) for JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Time to Reach Cmax (Tmax) for JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Systemic Clearance (CL/F) for JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Apparent Volume of Distribution at Steady State (Vss/F) for JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
measure: Number of Participants with Presence of Anti-Drug Antibodies to JNJ-79635322 and Daratumumab
timeFrame: Up to 3 Years and 3 months
Other outcomes:
Locations:
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
city: Wollongong
country: Australia
facility: Wollongong Hospital
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Barcelona
country: Spain
facility: Hosp. Clinic de Barcelona
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: