A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma or Previously Treated Amyloid Light-chain (AL) Amyloidosis

Official title

Phase 1, First-in-Human, Dose Escalation Study of JNJ-79635322, a Trispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma or Previously Treated AL Amyloidosis

Overview

The primary purpose of this study is to identify the recommended phase 2 dose (RP2D\[s\]) and schedule(s) to be safe for JNJ-79635322 in Part 1 (dose escalation), and to characterize the safety and tolerability of JNJ-79635322 at the RP2D(s) selected and in disease subgroups in Part 2 (dose expansion).

Interventions

• Drug JNJ-79635322
  JNJ-79635322 will be administered as SC injection.

Primary outcome measures

• Part 1: Number of Participants with Dose-limiting Toxicity (DLT) [Time frame: Up to 2 years 5 months]
• Parts 1 and 2: Number of Participants with Adverse Events (AEs) by Severity [Time frame: Up to 2 years 5 months]
• Part 2: Number of Participants with Abnormalities in Laboratory Values [Time frame: Up to 2 Years 5 months]

Secondary outcome measures (8)

• Serum Concentration of JNJ-79635322 [Time frame: Up to 2 Years 5 months]
• Number of Participants with Presence of Anti-Drug Antibodies to JNJ-79635322 [Time frame: Up to 2 Years 5 months]
• Preliminary Anticancer Activity of JNJ-79635322 as Defined by International Myeloma Working Group (IMWG) 2016 Response Criteria [Time frame: Up to 2 Years 5 months]
• Time to Response (TTR) as Defined by IMWG 2016 Response Criteria [Time frame: Up to 2 Years 5 months]
• Duration of Response (DOR) as Defined by IMWG 2016 Response Criteria [Time frame: Up to 2 Years 5 months]
• Part 2: Time to Response (TTR) as Defined by International Amyloidosis Consensus Criteria [Time frame: Up to 2 Years 5 months]
• Part 2: Duration of Response (DOR) as Defined by International Amyloidosis Consensus Criteria [Time frame: Up to 2 Years 5 months]
• Part 2: Preliminary Anticancer Activity of JNJ-79635322 as Defined by International Amyloidosis Consensus Criteria [Time frame: Up to 2 Years 5 months]

Eligibility criteria

Inclusion criteria

For participants with relapsed or refractory multiple myeloma:

• Have a documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
• Part 1: Have relapsed or refractory disease, have been treated with a proteasome inhibitor, immunomodulatory drug (IMiD) agent, and an anti-CD38-based therapy for the treatment of multiple myeloma (MM),and should have been treated with at least 3 prior lines of therapy, or are refractory to proteosome inhibitor, IMiD agent, and an anti-CD38-based therapy regardless of prior lines of therapy, Part 2: Have relapsed or refractory disease, have been treated with a PI, IMiD and an anti-CD38 based therapy
• Must have an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
• Have measurable disease at screening as defined by at least 1 of the following: a) Serum M-protein level greater than or equal to (>=) 0.5 grams per deciliter (g/dL); or b) Urine M-protein level >=200 milligrams (mg)/24 hours; or c) Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) >=10 milligrams per deciliter (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 (EMD) 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 and Computed Tomography (PET-CT) Scans (or whole body magnetic resonance imaging \[MRI\] approved by sponsor), and not previously radiated (Part 2C participants are not required to have measurable disease)

For participants with previously treated AL amyloidosis:

• Initial histopathological diagnosis of amyloidosis
• Participant who is not a candidate for available AL amyloidosis therapy with established clinical benefit and should have received at least 3 cycles of 1 prior line of therapy or a total of at least 2 cycles of 2 or more prior lines of therapy for AL amyloidosis
• Measurable disease at screening defined by at least 1 of the following: serum involved free light chain (iFLC) >=50 mg/L or difference between involved and uninvolved free light chains (dFLC) >=50 mg/L, or serum m-protein >= 0.5 g/dL
• One or more organs impacted by systemic AL amyloidosis
• Left ventricular ejection fraction (LVEF) >=45%

Exclusion criteria

For participants with relapsed or refractory multiple myeloma:

• Central Nervous System (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required
• Active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain amyloidosis
• Received a cumulative dose of corticosteroids equivalent to greater than (>) 140 mg of prednisone within the 14-day period before the start of study treatment administration
• Prior antitumor therapy as follows, in the specified time frame prior to the first dose of study treatment: (proteasome inhibitor \[PI\] therapy or radiotherapy within 14 days, immunomodulatory drug (IMiD) agent therapy within 7 days, gene-modified adoptive cell therapy within 90 days \[not applicable for Part 2C participants\], or CD3-redirecting therapy within 21 days\[not applicable for Part 2B or 2C participants\])
• Prior allogeneic transplant within 6 months before the start of study treatment administration or autologous transplant within 12 weeks before the start of study treatment administration
• Live, attenuated vaccine within 4 weeks before the first dose of study treatment
• Non-hematologic toxicity from prior anticancer therapy that has not resolved to baseline levels or to Grade less than or equal to (<=) 1 (except alopecia, tissue post-RT fibrosis \[any grade\] or peripheral neuropathy to Grade <=3)
• 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, autoimmune disease, serious active viral or bacterial infection, uncontrolled systemic fungal infection, cardiac conditions (myocardial infarction <=6 months prior to enrollment, New York Heart Association stage III or IV congestive heart failure, et cetera)
• Part 2C: have progressive disease or refractory disease per IMWG after CAR-T administration

For participants with previously treated AL amyloidosis:

• CNS involvement or clinical signs of meningeal involvement of AL amyloidosis. If either is suspected, whole brain MRI and lumbar cytology are required
• Any form of non-AL amyloidosis, including but not limited to transthyretin (ATTR) amyloidosis
• Active plasma cell leukemia, Waldenstrom's macroglobulinemia, or POEMS syndrome
• Pulmonary compromise requiring supplemental oxygen use
• Any serious medical conditions such as: active viral, bacterial, fungal infection; active autoimmune disease; HIV infection, active hepatitis B or C infection, stroke or seizure within 6 months prior to first dose of study treatment, significant cardiovascular conditions
• Previous or current diagnosis of symptomatic multiple myeloma
• Macroglossia that impairs swallowing difficulty
• Received a cumulative dose of corticosteroids equivalent to > 140 mg of prednisone within the 14-day period before the start of study treatment administration
• Prior antitumor therapy within 21 days prior to the first dose of study treatment (PI therapy or radiotherapy within 14 days, IMiD agent therapy within 7 days, gene-modified adoptive cell therapy within 90 days, or CD3-redirecting therapy within 21 days)
• Prior allogeneic transplant within 6 months before the start of study treatment administration or autologous transplant within 12 weeks before the start of study treatment administration
• Live, attenuated vaccine within 4 weeks before the first dose of study treatment
• Non-hematologic toxicity from prior anticancer therapy that has not resolved to baseline levels or to <=1 (except alopecia, tissue post-RT fibrosis \[any grade\] or peripheral neuropathy to Grade <=3)

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

United States · 9 centers

• City of Hope — Duarte
• City of Hope Orange County Lennar Foundation Cancer Center — Irvine
• University of California San Francisco — San Francisco
• Colorado Blood Cancer Institute — Denver
• Icahn School of Medicine at Mt. Sinai — New York
• Memorial Sloan Kettering Cancer Center — New York
• Levine Cancer Institute — Charlotte
• University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Me — Philadelphia
• … and 1 more center

Spain · 5 centers

• Hosp. Univ. Germans Trias I Pujol — Badalona
• Hosp Clinic de Barcelona — Barcelona
• Hosp Univ Fund Jimenez Diaz — Madrid
• Clinica Univ. de Navarra — Pamplona
• Hosp Clinico Univ de Salamanca — Salamanca

France · 4 centers

• CHU Nantes — Nantes
• CHU Lyon Sud — Pierre-Bénite
• Chu Rennes Hopital Pontchaillou — Rennes
• Institut Claudius Regaud — Toulouse

Belgium · 3 centers

• UZ Antwerpen — Edegem
• UZ Gent — Ghent
• CHU de Liege — Liège

Japan · 3 centers

• Japanese Red Cross Medical Center — Shibuya City
• Osaka University Hospital — Suita-shi
• The Cancer Institute Hospital of JFCR — Tokyo

Netherlands · 3 centers

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

United Kingdom · 2 centers

• University College Hospital — London
• Royal Marsden Hospital — Sutton

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: NCT05652335 · CR109234 · 79635322MMY1001 · 2022-001465-12 · 2023-503679-12-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗