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A Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma

Primary Purpose

Relapsed or Refractory Multiple Myeloma

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Forimtamig
Carfilzomib
Daratumumab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed or Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Life expectancy of at least 12 weeks Documented diagnosis of MM according to the IMWG diagnostic criteria Evidence of progressive disease based on Investigator's determination of response by IMWG criteria on or after last dosing regimen Measurable disease AEs from prior anti-cancer therapy resolved to Grade ≤ 1, Adequate organ functions Exclusion Criteria: Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the last dose of study drug Plasma cell leukemia with circulating plasma cell count ≥ 5% or >500/microliter (µL) Participants with current amyloidosis Participants with myelodysplastic syndrome Prior treatment with monoclonal antibody (mAb) and antibody-drug conjugate within 4 weeks or 5 half-lives of the drug, whichever is shorter Prior anti-cancer therapy (chemotherapy, small molecule/tyrosine kinase inhibitors, radiotherapy) within 14 days prior to first forimtamig administration Prior solid organ transplantation Active auto-immune disease or flare within 6 months prior to start of study treatment Known or suspected chronic active Epstein-Barr virus (EBV) infection Hepatitis B virus (HBV) infection Acute or chronic hepatitis C virus (HCV) infection Known history of HIV seropositivity Live vaccine(s) within one month prior to start of the treatment Participants not fully vaccinated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per local recommendations Previous refractoriness to carfilzomib Participants who discontinued prior carfilzomib treatment due to treatment-related toxicity Participants with known liver cirrhosis

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm 9

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib

    Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib

    Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib

    Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab

    Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab

    Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab

    Dose Expansion Phase: Forimtamig

    Dose Expansion Phase: Forimtamig + Carfilzomib

    Dose Expansion Phase: Forimtamig + Daratumumab

    Arm Description

    Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression.

    Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.

    Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.

    Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

    Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

    Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

    Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase until disease progression or completion of 12 months of treatment, whichever occurs first.

    Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression.

    Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants with Adverse Events (AEs)
    Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria
    Complete Response (CR)/Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria
    Rate of Very Good Partial Response (VGPR) or Better as Determined by the Investigator per IMWG Criteria

    Secondary Outcome Measures

    Progression-Free Survival (PFS) as Determined by the Investigator per IMWG Criteria
    Duration of Response (DoR) for Participants who Achieve a Partial Response (PR) or Better as Determined by the Investigator per IMWG Criteria
    Time to First Response as Determined by the Investigator per IMWG Criteria
    Time to Best Response as Determined by the Investigator per IMWG Criteria
    Overall Survival (OS) as Determined by the Investigator per IMWG Criteria
    Serum Concentration of Forimtamig
    Percentage of Participants with Anti-Drug Antibodies (ADAs) to Forimtamig

    Full Information

    First Posted
    September 20, 2023
    Last Updated
    October 18, 2023
    Sponsor
    Hoffmann-La Roche
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06055075
    Brief Title
    A Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma
    Official Title
    An Open-Label, Randomized Phase IB/II Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 30, 2023 (Anticipated)
    Primary Completion Date
    June 10, 2027 (Anticipated)
    Study Completion Date
    June 10, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Hoffmann-La Roche

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the safety, tolerability, and preliminary anti-tumor activity of forimtamig when administered alone or in combination with carfilzomib or daratumumab or other combination partners in participants with relapsed or refractory multiple myeloma (r/r MM). The study consists of two phases: a dose exploration phase and a dose-expansion phase.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Relapsed or Refractory Multiple Myeloma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    316 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib
    Arm Type
    Experimental
    Arm Description
    Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression.
    Arm Title
    Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib
    Arm Type
    Experimental
    Arm Description
    Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.
    Arm Title
    Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib
    Arm Type
    Experimental
    Arm Description
    Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.
    Arm Title
    Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab
    Arm Type
    Experimental
    Arm Description
    Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
    Arm Title
    Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab
    Arm Type
    Experimental
    Arm Description
    Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
    Arm Title
    Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab
    Arm Type
    Experimental
    Arm Description
    Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
    Arm Title
    Dose Expansion Phase: Forimtamig
    Arm Type
    Experimental
    Arm Description
    Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase until disease progression or completion of 12 months of treatment, whichever occurs first.
    Arm Title
    Dose Expansion Phase: Forimtamig + Carfilzomib
    Arm Type
    Experimental
    Arm Description
    Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression.
    Arm Title
    Dose Expansion Phase: Forimtamig + Daratumumab
    Arm Type
    Experimental
    Arm Description
    Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression.
    Intervention Type
    Drug
    Intervention Name(s)
    Forimtamig
    Intervention Description
    Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.
    Intervention Type
    Drug
    Intervention Name(s)
    Carfilzomib
    Intervention Description
    Carfilzomib will be administered via IV infusion in combination with forimtamig.
    Intervention Type
    Drug
    Intervention Name(s)
    Daratumumab
    Intervention Description
    Daratumumab will be administered via SC injection in combination with forimtamig.
    Primary Outcome Measure Information:
    Title
    Percentage of Participants with Adverse Events (AEs)
    Time Frame
    Up to approximately 24 months
    Title
    Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria
    Time Frame
    Up to approximately 24 months
    Title
    Complete Response (CR)/Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria
    Time Frame
    Up to approximately 24 months
    Title
    Rate of Very Good Partial Response (VGPR) or Better as Determined by the Investigator per IMWG Criteria
    Time Frame
    Up to approximately 24 months
    Secondary Outcome Measure Information:
    Title
    Progression-Free Survival (PFS) as Determined by the Investigator per IMWG Criteria
    Time Frame
    Up to approximately 24 months
    Title
    Duration of Response (DoR) for Participants who Achieve a Partial Response (PR) or Better as Determined by the Investigator per IMWG Criteria
    Time Frame
    Up to approximately 24 months
    Title
    Time to First Response as Determined by the Investigator per IMWG Criteria
    Time Frame
    Up to approximately 24 months
    Title
    Time to Best Response as Determined by the Investigator per IMWG Criteria
    Time Frame
    Up to approximately 24 months
    Title
    Overall Survival (OS) as Determined by the Investigator per IMWG Criteria
    Time Frame
    Up to approximately 24 months
    Title
    Serum Concentration of Forimtamig
    Time Frame
    Up to approximately 24 months
    Title
    Percentage of Participants with Anti-Drug Antibodies (ADAs) to Forimtamig
    Time Frame
    Up to approximately 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Life expectancy of at least 12 weeks Documented diagnosis of MM according to the IMWG diagnostic criteria Evidence of progressive disease based on Investigator's determination of response by IMWG criteria on or after last dosing regimen Measurable disease AEs from prior anti-cancer therapy resolved to Grade ≤ 1, Adequate organ functions Exclusion Criteria: Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the last dose of study drug Plasma cell leukemia with circulating plasma cell count ≥ 5% or >500/microliter (µL) Participants with current amyloidosis Participants with myelodysplastic syndrome Prior treatment with monoclonal antibody (mAb) and antibody-drug conjugate within 4 weeks or 5 half-lives of the drug, whichever is shorter Prior anti-cancer therapy (chemotherapy, small molecule/tyrosine kinase inhibitors, radiotherapy) within 14 days prior to first forimtamig administration Prior solid organ transplantation Active auto-immune disease or flare within 6 months prior to start of study treatment Known or suspected chronic active Epstein-Barr virus (EBV) infection Hepatitis B virus (HBV) infection Acute or chronic hepatitis C virus (HCV) infection Known history of HIV seropositivity Live vaccine(s) within one month prior to start of the treatment Participants not fully vaccinated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per local recommendations Previous refractoriness to carfilzomib Participants who discontinued prior carfilzomib treatment due to treatment-related toxicity Participants with known liver cirrhosis
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Reference Study ID Number: BP43437 https://forpatients.roche.com/
    Phone
    888-662-6728 (U.S. Only)
    Email
    global-roche-genentech-trials@gene.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Clinical Trials
    Organizational Affiliation
    Hoffmann-La Roche
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

    Learn more about this trial

    A Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma

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