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

Overview

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

• Drug JNJ-79635322
  JNJ-79635322 will be administered subcutaneously.
• Drug Daratumumab
  Daratumumab will be administered subcutaneously.
• Drug Pomalidomide
  Pomalidomide will be administered orally.
• Drug Lenalidomide
  Lenalidomide will be administered orally.

Primary outcome measures

• Part 1: Number of Participants with Dose-limiting Toxicity (DLT) [Time frame: Up to 28 days]
• Number of Participants with Adverse Events (AEs) by Severity [Time frame: Up to 3 Years and 3 months]
• Number of Participants with Clinically Significant Laboratory Abnormalities [Time frame: Up to 3 Years and 3 months]

Secondary outcome measures (12)

• Percentage of Participants With Overall Response Rate [Time frame: Up to 3 Years and 3 months]
• Duration of Response (DOR) [Time frame: Up to 3 Years and 3 months]
• Time to Response (TTR) [Time frame: Up to 3 Years and 3 months]
• Serum Concentration of JNJ-79635322 and Daratumumab [Time frame: 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 [Time frame: 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 [Time frame: Up to 3 Years and 3 months]
• Area Under the Serum Concentration Time Curve During the Dosing Interval (AUCtau) for JNJ-79635322 and Daratumumab [Time frame: Up to 3 Years and 3 months]
• Maximum Serum Concentration (Cmax) for JNJ-79635322 and Daratumumab [Time frame: Up to 3 Years and 3 months]
• Half Life (T1/2) for JNJ-79635322 and Daratumumab [Time frame: Up to 3 Years and 3 months]
• Time to Reach Cmax (Tmax) for JNJ-79635322 and Daratumumab [Time frame: Up to 3 Years and 3 months]
• Systemic Clearance (CL/F) for JNJ-79635322 and Daratumumab [Time frame: Up to 3 Years and 3 months]
• Apparent Volume of Distribution at Steady State (Vss/F) for JNJ-79635322 and Daratumumab [Time frame: Up to 3 Years and 3 months]

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 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

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 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 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 5 centers

• Monash Medical Centre — Clayton
• St Vincents Hospital Melbourne — Fitzroy
• Peter MacCallum Cancer Centre — Melbourne
• Calvary Mater Newcastle Hospital — Waratah
• Wollongong Hospital — Wollongong

Israel · 4 centers

• Carmel Medical Center — Haifa
• Hadassah Medical Center — Jerusalem
• Sheba Medical Center — Ramat Gan
• Tel Aviv Sourasky Medical Center — Tel Aviv

Netherlands · 3 centers

• VU Medisch Centrum — Amsterdam
• Universitair Medisch Centrum Groningen — Groningen
• UMC Utrecht — Utrecht

United States · 2 centers

• Colorado Blood Cancer Institute — Denver
• Winship Cancer Institute Emory University — Atlanta

Spain · 2 centers

• Hosp. Clinic de Barcelona — Barcelona
• Hosp Clinico Univ de Salamanca — Salamanca

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. PMID 41100731

Identifiers

NCT: NCT06768489 · 79635322MMY1002 · 79635322MMY1002 · 2024-515316-44-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗