A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide or in Combination With Pomalidomide for Multiple Myeloma

A Phase 1b Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide or in Combination With Pomalidomide for Multiple Myeloma

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).

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Daratumumab; Drug: Pomalidomide; Drug: JNJ-79635322

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Recruiting
    • Monash Medical Centre
  • Fitzroy, Australia, 3065
    • Recruiting
    • St Vincents Hospital Melbourne
  • Melbourne, Australia, 3000
    • Recruiting
    • Peter MacCallum Cancer Centre
  • Waratah, Australia, 2298
    • Recruiting
    • Calvary Mater Newcastle Hospital
  • Wollongong, Australia, 2500
    • Recruiting
    • Wollongong Hospital
• Israel
  • Haifa, Israel, 3436212
    • Recruiting
    • Carmel Medical Center
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • VU Medisch Centrum
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Universitair Medisch Centrum Groningen
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • UMC Utrecht
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hosp. Clinic de Barcelona
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp Clinico Univ de Salamanca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Regimen B: JNJ-79635322+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.	Drug: Pomalidomide; Pomalidomide will be administered orally.; Drug: JNJ-79635322; JNJ-79635322 will be administered subcutaneously.
Experimental: Treatment Regimen A and C: JNJ-79635322+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/C). 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.	Drug: Daratumumab; Daratumumab will be administered subcutaneously.; Drug: JNJ-79635322; JNJ-79635322 will be administered subcutaneously.
Experimental: Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination; Participants with NDMM will receive a dose of JNJ-79635322 along with daratumumab and lenalidomide 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.	Drug: Lenalidomide; Lenalidomide will be administered orally.; Drug: Daratumumab; Daratumumab will be administered subcutaneously.; Drug: JNJ-79635322; JNJ-79635322 will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) by Severity	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.	Up to 3 Years and 3 months
Number of Participants with Clinically Significant Laboratory Abnormalities	Participants with clinically significant laboratory abnormalities (hematology and chemistry) will be reported.	Up to 3 Years and 3 months
Part 1: Number of Participants with Dose-limiting Toxicity (DLT)	DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Overall Response Rate	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.	Up to 3 Years and 3 months
Duration of Response (DOR)	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.	Up to 3 Years and 3 months
Time to Response (TTR)	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.	Up to 3 Years and 3 months
Serum Concentration of JNJ-79635322 and Daratumumab	Serum samples will be analyzed to determine concentrations of JNJ-79635322 and daratumumab.	Up to 3 Years and 3 months
Area Under the Serum Concentration Time Curve from Time Zero to Infinity (AUCinf) for JNJ-79635322 and Daratumumab	AUCinf for JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months
Area Under the Serum Concentration Time Curve from Time Zero to the Last Measurable Concentration [AUC(0-t)] for JNJ-79635322 and Daratumumab	AUC(0-t) for JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months
Area Under the Serum Concentration Time Curve During the Dosing Interval (AUCtau) for JNJ-79635322 and Daratumumab	AUCtau for JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months
Maximum Serum Concentration (Cmax) for JNJ-79635322 and Daratumumab	Cmax for JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months
Half Life (T1/2) for JNJ-79635322 and Daratumumab	T1/2 for JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months
Time to Reach Cmax (Tmax) for JNJ-79635322 and Daratumumab	Tmax for JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months
Systemic Clearance (CL/F) for JNJ-79635322 and Daratumumab	CL/F for JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months
Apparent Volume of Distribution at Steady State (Vss/F) for JNJ-79635322 and Daratumumab	Vss/F for JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months
Number of Participants with Presence of Anti-Drug Antibodies to JNJ-79635322 and Daratumumab	Participants with anti-drug antibodies to JNJ-79635322 and daratumumab will be reported.	Up to 3 Years and 3 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Pillarisetti K, Yang D, Luistro L, Yao J, Smith M, Vulfson P, Testa JS, Ponticiello R, Brodeur S, Heidrich B, Packman K, Singh S, Attar R, Elsayed Y, Philippar U. Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models. Blood. 2026 Feb 19;147(8):834-847. doi: 10.1182/blood.2025030027.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2024
• Primary Completion (Estimated): November 19, 2027
• Study Completion (Estimated): November 23, 2028

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: January 9, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; pomalidomide; daratumumab
• Other Study ID Numbers: 79635322MMY1002 (Other Identifier: Janssen Research & Development, LLC); 2024-515316-44-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes