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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory Multiple Myeloma; Previously Treated Amyloid Light-chain (AL) Amyloidosis
• Intervention / Treatment: Drug: JNJ-79635322

Detailed Description

The study will be conducted in 2 parts: dose escalation (Part 1) and dose expansion (Part 2). It will evaluate safety, tolerability, pharmacokinetics and preliminary antitumor activity of JNJ-79635322 administered to adult participants with relapsed or refractory multiple myeloma. The overall safety of the study drug will be assessed by physical examinations, Eastern Cooperative Oncology Group performance status, laboratory tests, vital signs, electrocardiograms, adverse event monitoring, and concomitant medication usage. Disease evaluations will include peripheral blood and bone marrow assessments at screening (performed within 28 days) and to confirm stringent complete response (sCR), complete response (CR), or relapse from CR. The end of study (study completion) is defined as the last study assessment for the last participant on study.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Recruiting
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • Recruiting
    • UZ Gent
  • Liege, Belgium, 4000
    • Recruiting
    • CHU de Liège
• France
  • Nantes, France, 44093
    • Recruiting
    • CHU Nantes
  • Pierre benite, France, 69495
    • Recruiting
    • CHU Lyon Sud
  • Rennes, France, 35000
    • Recruiting
    • Chu Rennes Hopital Pontchaillou
  • Toulouse, France, 31100
    • Recruiting
    • Institut Claudius Regaud
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • VUMC Amsterdam
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • UMC Utrecht
• Spain
  • Badalona, Spain, 08916
    • Recruiting
    • Hosp. Univ. Germans Trias I Pujol
  • Barcelona, Spain, 08036
    • Recruiting
    • Hosp. Clinic de Barcelona
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp. Univ. Fund. Jimenez Diaz
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp. Clinico Univ. de Salamanca
• United Kingdom
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • University College Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Recruiting
    • Royal Marsden Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope Orange County Lennar Foundation Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• 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
• 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

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) >=50mg/L or difference between involved and uninvolved free light chains (dFLC) >=50mg/L, or serum m-protein >= 0.5g/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 within 21 days 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, 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 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)

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)

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; Participants will receive JNJ-79635322. The dose will be escalated sequentially until the recommended phase 2 dose (RP2D) regimen(s) have been identified.	Drug: JNJ-79635322; JNJ-79635322 will be administered as SC injection.
Experimental: Part 2: Dose Expansion; Participants will receive JNJ-79635322 at the RP2D regimen(s) determined in Part 1.	Drug: JNJ-79635322; JNJ-79635322 will be administered as SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 2 years 5 months
Parts 1 and 2: Number of Participants with Adverse Events (AEs) by Severity	An adverse event 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 2 years 5 months
Part 2: Number of Participants with Abnormalities in Laboratory Values	Number of participants with abnormalities in laboratory values (hematology and chemistry) will be reported.	Up to 2 Years 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of JNJ-79635322	Serum samples will be analyzed to determine concentrations of JNJ-79635322.	Up to 2 Years 5 months
Number of Participants with Presence of Anti-Drug Antibodies to JNJ-79635322	Number of participants with presence of anti-drug antibodies to JNJ-79635322 will be reported.	Up to 2 Years 5 months
Preliminary Anticancer Activity of JNJ-79635322 as Defined by International Myeloma Working Group (IMWG) 2016 Response Criteria	Preliminary anticancer activity of JNJ-79635322 will be assessed according to the International Myeloma Working Group (IMWG) 2016 response criteria.	Up to 2 Years 5 months
Time to Response (TTR) as Defined by IMWG 2016 Response Criteria	TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation at which the participant has met all criteria for partial response (PR) or better as defined by IMWG 2016 response criteria.	Up to 2 Years 5 months
Duration of Response (DOR) as Defined by IMWG 2016 Response Criteria	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), per IMWG 2016 response criteria, or death due to any cause, whichever occurs first.	Up to 2 Years 5 months
Part 2: Time to Response (TTR) as Defined by International Amyloidosis Consensus Criteria	TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation at which the participant has met all criteria for PR or better as defined by International Amyloidosis Consensus Criteria.	Up to 2 Years 5 months
Part 2: Duration of Response (DOR) as Defined by International Amyloidosis Consensus Criteria	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), per International Amyloidosis Consensus Criteria or death due to any cause, whichever occurs first.	Up to 2 Years 5 months
Part 2: Preliminary Anticancer Activity of JNJ-79635322 as Defined by International Amyloidosis Consensus Criteria	Preliminary anticancer activity of JNJ-79635322 will be assessed according to the International Amyloidosis Consensus Criteria.	Up to 2 Years 5 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2022
• Primary Completion (Estimated): April 18, 2025
• Study Completion (Estimated): April 10, 2026

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Proteostasis Deficiencies; Multiple Myeloma; Neoplasms, Plasma Cell; Amyloidosis
• Other Study ID Numbers: CR109234; 2022-001465-12 (EudraCT Number); 79635322MMY1001 (Other Identifier: Janssen Research & Development, LLC); 2023-503679-12-00 (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 the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/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: No
• Studies a U.S. FDA-regulated device product: No