A Study Evaluating The Safety And Pharmacokinetics Of Escalating Doses Of RO7297089 In Patients With Relapsed Or Refractory Multiple Myeloma

An Open-Label, Multicenter, Phase I Trial Evaluating The Safety And Pharmacokinetics Of Escalating Doses Of RO7297089 In Patients With Relapsed Or Refractory Multiple Myeloma

This is a first-in-human Phase I, open-label, multicenter, global, dose-escalation study designed to evaluate the safety, tolerability, and pharmacokinetics of RO7297089 and make a preliminary assessment of anti-tumor activity in patients with R/R MM for whom no established therapy for MM is appropriate and available or who are intolerant to those established therapies.

Study Overview

• Status: Completed
• Conditions: Refractory Multiple Myeloma; Relapsed Multiple Myeloma
• Intervention / Treatment: Drug: RO7297089

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Liverpool, New South Wales, Australia, 2170
      • LIVERPOOL HOSPITAL; HAEMATOLOGY; Ingham Institute for Medical Research
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital; Haematology Clinical Trials
    • Fitzroy, South Australia, Australia, 3065
      • St. Vincent's Hospital Melbourne
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter Mac Callum Cancer Center
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet
  • Vejle, Denmark, 7100
    • Vejle Sygehus; Onkologisk Afdeling
• Norway
  • Oslo, Norway, 0450
    • Oslo Universitetssykehus HF; Ullevål sykehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• R/R MM for which no established therapy for MM is appropriate and available or be intolerant to those established therapies
• Measurable disease

Exclusion criteria:

• Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate for the treatment of cancer within 4 weeks before first RO7297089 infusion
• Prior treatment with systemic immunotherapeutic agents within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first RO7297089 infusion
• Prior treatment with CAR-T therapy within 90 days before first study drug administration
• Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first RO7297089 infusion
• Autologous stem cell transplantation within 100 days prior to first RO7297089 infusion
• Allogeneic stem cell transplantation within 180 days prior to first RO7297089 infusion or requiring immunosuppression for treatment or prophylaxis of graft versus host disease
• Primary or secondary plasma cell leukemia
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring treatment with IV anti-microbial therapy within 14 days prior to first RO7297089 infusion
• Significant cardiovascular disease
• Current CNS involvement by MM

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm A Flat Dose Escalation: RO7297089; Participants in Arm A will receive the target dose of RO7297089 as a flat dose at each scheduled study drug administration visit	Drug: RO7297089; RO7297089 will be given via intravenous (IV) infusion
EXPERIMENTAL: Arm B Split Dose Escalation: RO7297089; Participants in Arm B will receive the first target dose of RO7297089 as a split dose divided over two days (Days 1 and 2). The full target dose will be administered at subsequent study drug administration visits.	Drug: RO7297089; RO7297089 will be given via intravenous (IV) infusion
EXPERIMENTAL: Arm C Step Dose Escalation: RO7297089; Participants in Arm C will receive the first cycle of RO7297089 as a single-step dose escalation. The Cycle 1 Day 1 dose will be lower than the target dose. The full target dose will be administered at subsequent study drug administration visits.	Drug: RO7297089; RO7297089 will be given via intravenous (IV) infusion
EXPERIMENTAL: Phase I Expansion Stage: RO7297089; After dose escalation has been completed, approximately 30 patients will be enrolled in the expansion stage. Participants will receive RO7297089 at the recommended phase 2 dose (at or below the maximum tolerated dose).	Drug: RO7297089; RO7297089 will be given via intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with Adverse Events (AEs), including Dose Limiting Toxicities (DLTs)	Adverse event severity will be graded according to NCI CTCAE v5.0	Baseline up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of RO7297089	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)
Area under the Curve (AUC) of RO7297089	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)
Maximum Concentration Observed (Cmax) of RO7297089	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)
Time to Maximum Concentration Observed (tmax) of RO7297089	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)
Minimum Concentration Observed (Cmin) of RO7297089	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)
Volume of Distribution at Steady State of RO7297089	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)
Half-life of RO7297089	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)
Total clearance of RO7297089	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)
Objective Response Rate (ORR)	ORR is defined as a Stringent Complete Response (Scr), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) as determined by the Investigator according to International Myeloma Working Group (IMWG) Uniform Response Criteria	Baseline up to approximately 3 years
Duration Of Response (DOR)	DOR is defined as the time from the first occurrence of a documented Objective Response to Disease Progression or death from any cause (whichever occurs first), as determined by the Investigator according to IMWG Uniform Response Criteria	Baseline up to approximately 3 years
Prevalence Of Anti-Drug Antibodies (ADAs)	Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit	Baseline up to approximately 3 years (detailed time frame provided in description)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 8, 2020
• Primary Completion (ACTUAL): February 16, 2022
• Study Completion (ACTUAL): February 16, 2022

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (ACTUAL): June 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 2, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: GO41582

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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/members/ourmembers/). 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)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes