Phase I, 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

Study Identifier:
79635322MMY1001
CT.gov Identifier:
NCT05652335
EudraCT Identifier:
2022-001465-12
EU Trial (CTIS) Number:
2023-503679-12-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study Summary

To assess safety, tolerability, pharmacokinetics and efficacy of JNJ-79635322 in patients with relapsed or refractory multiple myeloma.

Adverse events (AEs) were graded by CTCAE v5.0; CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Overall response rate (ORR) was assessed by IMWG criteria.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Multiple Myeloma
  • Amyloidosis
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part 1
    • Read More
  • Drug: Experimental: Part 2
  • Drug: Intervention/treatment:
  • Drug: Escalating fixed Q2W or Q4W SC doses (0.4-300 mg) were explored, including 100 mg Q4W, the putative recommended phase 2 dose (RP2D). Pts received 1 step-up dose (SUD) (5 mg) prior to receiving the 100 mg Q4W dose, allowing faster full dose initiation and attenuation of cytokine release syndrome (CRS) risk.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • FFor 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 tha

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Gala Vega Achabal
    Status
    Recruiting
    Condition(s) Treated at Site
    Multiple Myeloma
    Amyloidosis