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

NCT06768489 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 79635322MMY10022024-515316-44-00
• Study Type: interventional
• Target: 140
• Locations: 4 countries
• Sites: 14

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).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• 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

• 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

Secondary Outcomes (13)

• Percentage of Participants With Overall Response Rate

  Up to 3 Years and 3 months

• Duration of Response (DOR)

  Up to 3 Years and 3 months

• Time to Response (TTR)

  Up to 3 Years and 3 months

• Serum Concentration 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

  Up to 3 Years and 3 months

Study Arms (3)

Treatment Regimen A and C: JNJ-79635322+Daratumumab

EXPERIMENTAL

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: JNJ-79635322; Drug: Daratumumab

Treatment Regimen B: JNJ-79635322+Pomalidomide

EXPERIMENTAL

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: JNJ-79635322; Drug: Pomalidomide

Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination

EXPERIMENTAL

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: JNJ-79635322; Drug: Daratumumab; Drug: Lenalidomide

Interventions

JNJ-79635322 DRUG

JNJ-79635322 will be administered subcutaneously.

Treatment Regimen A and C: JNJ-79635322+Daratumumab; Treatment Regimen B: JNJ-79635322+Pomalidomide; Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination

Daratumumab DRUG

Daratumumab will be administered subcutaneously.

Treatment Regimen A and C: JNJ-79635322+Daratumumab; Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination

Pomalidomide DRUG

Pomalidomide will be administered orally.

Treatment Regimen B: JNJ-79635322+Pomalidomide

Lenalidomide DRUG

Lenalidomide will be administered orally.

Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (14)

Monash Medical Centre

Clayton, 3168, Australia

RECRUITING

St Vincents Hospital Melbourne

Fitzroy, 3065, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

RECRUITING

Calvary Mater Newcastle Hospital

Waratah, 2298, Australia

RECRUITING

Wollongong Hospital

Wollongong, 2500, Australia

RECRUITING

Carmel Medical Center

Haifa, 3436212, Israel

RECRUITING

Hadassah Medical Center

Jerusalem, 9112001, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, 52621, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

RECRUITING

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

RECRUITING

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

UMC Utrecht

Utrecht, 3584 CX, Netherlands

RECRUITING

Hosp. Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 41100731 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; pomalidomide; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: January 10, 2025
• Study Start: December 4, 2024
• Primary Completion (Estimated): November 19, 2027
• Study Completion (Estimated): November 23, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

NL (3); AU (5); ES (2); IL (4)