A Study of JNJ-79635322 in Combination With Daratumumab or Pomalidomide for Multiple Myeloma

Phase 1

Recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: JNJ-79635322; Drug: Daratumumab; Drug: Pomalidomide

• Registration Number: NCT06768489
• Lead Sponsor: Janssen Research & Development, LLC

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 either daratumumab or pomalidomide; and for Part 2 (Dose Expansion) is to further define the safety and tolerability of JNJ-79635322 combination treatment regimens at selected RP2D(s).

Detailed Description

Not available

Study Timeline

• Study Start: 2024-12-04
• Study First Submitted: 2024-12-23
• Study First Submitted QC: 2025-01-09
• Study First Posted: 2025-01-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-25
• Primary Completion: 2028-03-31
• Study Completion: 2028-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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
• 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 etcetera)
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Regimen A: JNJ-79635322+Daratumumab	Daratumumab	Participants who have received 1-3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (Treatment regimen A1) will receive a dose of JNJ-79635322 along with daratumumab to establish the recommended phase 2 doses (RP2D\[s\]) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Based on the study evaluation team (SET) decision, enrollment may proceed in participants with newly diagnosed multiple myeloma (NDMM) (Treatment regimen A2). Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
Treatment Regimen B: JNJ-79635322+Pomalidomide	JNJ-79635322	Participants who 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 will receive a dose of JNJ-79635322 along with pomalidomide to establish the RP2D(s) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
Treatment Regimen B: JNJ-79635322+Pomalidomide	Pomalidomide	Participants who 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 will receive a dose of JNJ-79635322 along with pomalidomide to establish the RP2D(s) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
Treatment Regimen A: JNJ-79635322+Daratumumab	JNJ-79635322	Participants who have received 1-3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (Treatment regimen A1) will receive a dose of JNJ-79635322 along with daratumumab to establish the recommended phase 2 doses (RP2D\[s\]) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Based on the study evaluation team (SET) decision, enrollment may proceed in participants with newly diagnosed multiple myeloma (NDMM) (Treatment regimen A2). Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.

Primary Outcome Measures

Name	Time	Method
Part 1: Number of Participants with Dose-limiting Toxicity (DLT)	Up to 3 Years and 3 months	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 Outcome Measures

Name	Time	Method
Percentage of Participants With Overall Response Rate	Up to 3 Years and 3 months	Overall response rate is defined as percentage of participants who have a partial response (PR) or better evaluated by the investigator as per international myeloma working group (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.
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 participant has met all criteria for PR or better as defined by IMWG 2016 response 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.

Trial Locations

Locations (13)

Monash Medical Centre; 🇦🇺 Clayton, Australia

VU Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Universitair Medisch Centrum Groningen; 🇳🇱 Groningen, Netherlands

St Vincents Hospital Melbourne; 🇦🇺 Fitzroy, Australia

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Australia

Calvary Mater Newcastle Hospital; 🇦🇺 Waratah, Australia

Carmel Medical Center; 🇮🇱 Haifa, Israel

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv Yafo, Israel

UMC Utrecht; 🇳🇱 Utrecht, Netherlands

Hosp. Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hosp Clinico Univ de Salamanca; 🇪🇸 Salamanca, Spain