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A Study to Evaluate the Safety, Pharmacokinetics, and Activity of XmAb24306 in Combination With Cevostamab in Participants With Relapsed/Refractory Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Cevostamab
XmAb24306
Tocilizumab
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for 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 Participants must have received a minimum of 3 prior lines of therapy, including at least one PI, one IMiD, and an anti-CD38 monoclonal antibody. Documented evidence of progressive disease on or after the last prior therapy, or participants who were intolerant to the last prior therapy. Measurable disease, as defined by the protocol Participants agree to follow contraception or abstinence requirements as defined in the protocol Exclusion Criteria: Any anti-cancer therapy within 3 weeks prior to initiation of study treatment with exception defined by the protocol Participants with autologous stem cell transplantation (SCT) within 100 days prior to first dose of study treatment Participants with prior allogeneic SCT or solid organ transplantation Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) Active or history of autoimmune disease Participants with current or history of Central Nervous System (CNS) disease, or current CNS involvement by Multiple Myeloma (MM) Significant cardiovascular disease Participants with known clinically significant liver disease Symptomatic active pulmonary disease requiring supplemental oxygen Known active infection requiring intravenous anti-microbial therapy within 14 days prior to first study drug administration Any episode of active, symptomatic COVID-19 infection, or requiring treatment with IV antivirals for COVID-19 (not including COVID-19 primary prophylaxis) within 14 days, prior to first study treatment Other protocol defined inclusion/exclusion criteria may apply

Sites / Locations

  • Royal Adelaide HospitalRecruiting
  • Peter Maccallum Cancer CentreRecruiting
  • Alfred HospitalRecruiting
  • Evangelismos General Hospital of AthensRecruiting
  • University of Athens Medical School - Regional General Hospital AlexandraRecruiting
  • Rabin Medical Center-Golda Campus - HasharonRecruiting
  • Tel Aviv Sourasky Medical Center PPDSRecruiting
  • Severance Hospital, Yonsei UniversityRecruiting
  • Asan Medical Center - PPDSRecruiting
  • Oslo University Hospital RikshospitaletRecruiting
  • Clinica Universidad de NavarraRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A: Dose-Escalation and Expansion: XmAb24306+Cevostamab

Arm B: Single-Agent Cevostamab Expansion

Arm Description

Participants will receive escalating doses of XmAb24306 with a fixed dose regimen for cevostamab up to the maximum tolerated dose (MTD). After dose escalation has been completed, up to two expansion cohorts each investigating different XmAb24306 doses in combination with cevostamab may be enrolled.

Participants will receive cevostamab alone.

Outcomes

Primary Outcome Measures

Percentage of Participants with Adverse Events (AEs)
Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), and Cytokine Release Syndrome (CRS), will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

Secondary Outcome Measures

Serum Concentration of XmAb24306
Serum Concentration of Cevostamab
Objective Response Rate (ORR)
ORR will be determined by the investigator according to International Myeloma Working Group (IMWG) criteria.
Rate of Complete Response (CR)/ Stringent Complete Response (sCR)
Rate of CR/sCR will be determined by the investigator.
Rate of Very Good Partial Response (VGPR)
Rate of VGPR will be determined by the investigator.
Percentage of Participants With Anti-Drug Antibodies (ADA) to XmAb24306 and Cevostamab

Full Information

First Posted
December 2, 2022
Last Updated
October 12, 2023
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05646836
Brief Title
A Study to Evaluate the Safety, Pharmacokinetics, and Activity of XmAb24306 in Combination With Cevostamab in Participants With Relapsed/Refractory Multiple Myeloma
Official Title
A Phase Ib, Open-label, Multicenter Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Activity of XmAb24306 in Combination With Cevostamab in Patients With Relapsed/Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2023 (Actual)
Primary Completion Date
August 21, 2026 (Anticipated)
Study Completion Date
January 14, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

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

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and activity of XmAb24306 in combination with cevostamab in participants with relapsed/refractory multiple myeloma (R/R MM) who have received a minimum of three prior treatments, including at least one immunomodulatory drug (IMiD), one proteasome inhibitor (PI), and one anti-CD38 monoclonal antibody.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Dose-Escalation and Expansion: XmAb24306+Cevostamab
Arm Type
Experimental
Arm Description
Participants will receive escalating doses of XmAb24306 with a fixed dose regimen for cevostamab up to the maximum tolerated dose (MTD). After dose escalation has been completed, up to two expansion cohorts each investigating different XmAb24306 doses in combination with cevostamab may be enrolled.
Arm Title
Arm B: Single-Agent Cevostamab Expansion
Arm Type
Experimental
Arm Description
Participants will receive cevostamab alone.
Intervention Type
Drug
Intervention Name(s)
Cevostamab
Other Intervention Name(s)
RO7187797
Intervention Description
Cevostamab will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.
Intervention Type
Drug
Intervention Name(s)
XmAb24306
Other Intervention Name(s)
RO7310729
Intervention Description
XmAb24306 will be administered intravenously on a 28-day cycle, for up to one year of treatment depending on clinical response.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
Actemra, RoActemra
Intervention Description
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Primary Outcome Measure Information:
Title
Percentage of Participants with Adverse Events (AEs)
Description
Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), and Cytokine Release Syndrome (CRS), will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
Time Frame
Up to approximately 3 years
Secondary Outcome Measure Information:
Title
Serum Concentration of XmAb24306
Time Frame
Up to approximately 3 years
Title
Serum Concentration of Cevostamab
Time Frame
Up to approximately 3 years
Title
Objective Response Rate (ORR)
Description
ORR will be determined by the investigator according to International Myeloma Working Group (IMWG) criteria.
Time Frame
Up to approximately 3 years
Title
Rate of Complete Response (CR)/ Stringent Complete Response (sCR)
Description
Rate of CR/sCR will be determined by the investigator.
Time Frame
Up to approximately 3 years
Title
Rate of Very Good Partial Response (VGPR)
Description
Rate of VGPR will be determined by the investigator.
Time Frame
Up to approximately 3 years
Title
Percentage of Participants With Anti-Drug Antibodies (ADA) to XmAb24306 and Cevostamab
Time Frame
Up to approximately 3 years

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 Participants must have received a minimum of 3 prior lines of therapy, including at least one PI, one IMiD, and an anti-CD38 monoclonal antibody. Documented evidence of progressive disease on or after the last prior therapy, or participants who were intolerant to the last prior therapy. Measurable disease, as defined by the protocol Participants agree to follow contraception or abstinence requirements as defined in the protocol Exclusion Criteria: Any anti-cancer therapy within 3 weeks prior to initiation of study treatment with exception defined by the protocol Participants with autologous stem cell transplantation (SCT) within 100 days prior to first dose of study treatment Participants with prior allogeneic SCT or solid organ transplantation Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) Active or history of autoimmune disease Participants with current or history of Central Nervous System (CNS) disease, or current CNS involvement by Multiple Myeloma (MM) Significant cardiovascular disease Participants with known clinically significant liver disease Symptomatic active pulmonary disease requiring supplemental oxygen Known active infection requiring intravenous anti-microbial therapy within 14 days prior to first study drug administration Any episode of active, symptomatic COVID-19 infection, or requiring treatment with IV antivirals for COVID-19 (not including COVID-19 primary prophylaxis) within 14 days, prior to first study treatment Other protocol defined inclusion/exclusion criteria may apply
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: GO43980 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
Facility Information:
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Peter Maccallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Name
Evangelismos General Hospital of Athens
City
Athens
ZIP/Postal Code
106 76
Country
Greece
Individual Site Status
Recruiting
Facility Name
University of Athens Medical School - Regional General Hospital Alexandra
City
Athens
ZIP/Postal Code
115 28
Country
Greece
Individual Site Status
Recruiting
Facility Name
Rabin Medical Center-Golda Campus - Hasharon
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Individual Site Status
Recruiting
Facility Name
Tel Aviv Sourasky Medical Center PPDS
City
Tel Aviv-Yafo
ZIP/Postal Code
6423906
Country
Israel
Individual Site Status
Recruiting
Facility Name
Severance Hospital, Yonsei University
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Asan Medical Center - PPDS
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Oslo University Hospital Rikshospitalet
City
Oslo
ZIP/Postal Code
N - 0424
Country
Norway
Individual Site Status
Recruiting
Facility Name
Clinica Universidad de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting

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 to Evaluate the Safety, Pharmacokinetics, and Activity of XmAb24306 in Combination With Cevostamab in Participants With Relapsed/Refractory Multiple Myeloma

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