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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Refractory Multiple Myeloma, Relapsed Multiple Myeloma

Intervention / Treatment
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* Drug: RO7297089


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A Flat Dose Escalation: RO7297089<br>Participants in Arm A will receive the target dose of RO7297089 as a flat dose at each scheduled study drug administration visit | Drug: RO7297089<br>* RO7297089 will be given via intravenous (IV) infusion<br>|
| Experimental: Arm B Split Dose Escalation: RO7297089<br>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<br>* RO7297089 will be given via intravenous (IV) infusion<br>|
| Experimental: Arm C Step Dose Escalation: RO7297089<br>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<br>* RO7297089 will be given via intravenous (IV) infusion<br>|
| Experimental: Phase I Expansion Stage: RO7297089<br>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<br>* RO7297089 will be given via intravenous (IV) infusion<br>|

What is the study measuring?
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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) |