A Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of RO7425781 in Participants With Relapsed or Refractory Multiple Myeloma (r/r MM)

An Open-Label, Multicenter, Phase I Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of RO7425781 in Participants With Relapsed or Refractory Multiple Myeloma

Sponsors

Lead Sponsor: Hoffmann-La Roche

Source Hoffmann-La Roche
Brief Summary

This is a first-in-human, open-label, uncontrolled, multi-center, monotherapy, dose-escalation and dose expansion study. RO7425781 will be administered to participants with r/r MM for whom no standard-of-care treatment exists or who are intolerant to those established therapies. The study consists of two parts: dose-escalation of RO7425781 (Part 1) and a randomized dose expansion of RO7425781 (Part 2).

Overall Status Not yet recruiting
Start Date November 3, 2020
Completion Date June 10, 2022
Primary Completion Date June 10, 2022
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Percentage of Participants with Adverse Events (AEs) Up to 69 weeks
Percentage of Participants with Dose Limiting Toxicities (DLTs) Up to 69 weeks
Secondary Outcome
Measure Time Frame
Objective Response Rate (ORR) Up to 69 weeks
Duration of Response (DOR) Up to 69 weeks
Progression-Free Survival (PFS) Up to 69 weeks
Overall Survival (OS) Up to 69 weeks
Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7425781 Up to 69 weeks
Maximum concentration (Cmax) of RO7425781 Up to 69 weeks
Time of Maximum concentration (Tmax) of RO7425781 Up to 69 weeks
Minimum concentration (Cmin) of RO7425781 Up to 69 weeks
SC Bioavailability (F) of RO7425781 Up to 69 weeks
Apparent Clearance (CL/F) of RO7425781 Up to 69 weeks
Volume of distribution at steady state (Vss) of RO7425781 (IV only) Up to 69 weeks
Area under the curve (AUC) at various time intervals of RO7425781 Up to 69 weeks
Enrollment 240
Condition
Intervention

Intervention Type: Drug

Intervention Name: RO7425781

Description: RO7425781 will be administered via IV/SC infusion. The MTD/RP2D determined during Part I: Dose Escalation will be administered during Part II: Dose Expansion. RO7425781 will be administered as per the dosing schedule defined in Part I.

Eligibility

Criteria:

Inclusion Criteria: - Previously diagnosed with Multiple Myeloma (MM) based on standard criteria. - Dose Escalation Phase: Participants with r/r MM who have previously received therapy with an Immunomodulatory drug (IMiD) and Proteasome Inhibitor (PI) and are intolerant to or have no other option for standard-of-care treatment according to the Investigator. - Dose Expansion Phase: Participants with r/r MM who have received at least three prior treatments and are refractory to an IMiD, a PI, and a CD38-targeted therapy. - Life expectancy of at least 12 weeks. - Agreement to provide protocol-specific biopsy material. - AEs from prior anti-cancer therapy resolved to Grade =<1. - Measurable disease. - For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating eggs. - For male participants: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm. Exclusion Criteria: - Inability to comply with protocol-mandated hospitalization and activities restrictions. - Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the last dose of study drug. - Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate within 4 weeks before first RO7425781 infusion. - Prior treatment with systemic immunotherapeutic agents. - Treatment-related, immune-mediated AEs associated with prior immunotherapeutic agents. - Treatment with radiotherapy, 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 RO7425781 infusion. - Autologous or allogeneic stem cell transplantation (SCT) within 100 days prior to first RO7425781 infusion and/or signs of chronic graft versus host disease or ongoing immunosuppressive medication. - Prior solid organ transplantation. - Any medical condition or abnormality in clinical laboratory tests that, in the Investigator's or Medical Monitor's judgment, precludes the participant's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Clinical Trials Study Director Hoffmann-La Roche
Overall Contact

Last Name: Reference Study ID Number: BP42233 www.roche.com/about_roche/roche_worldwide.htm

Phone: 888-662-6728 (U.S. and Canada)

Email: [email protected]

Location
Facility:
Peter MacCallum Cancer Center | East Melbourne, Victoria, 3002, Australia
UZ Gent | Gent, 9000, Belgium
Rigshospitalet; Hæmatologisk Klinik | København Ø, 2100, Denmark
Instituto Clinico Humanitas; Med Onc & Hemat | Rozzano, Lombardia, 20089, Italy
Seoul National University Hospital | Seoul, 03080, Korea, Republic of
Asan Medical Center | Seoul, 05505, Korea, Republic of
Hospital Universitario Marques de Valdecilla; Servicio de Hematologia | Santander, Cantabria, 39008, Spain
Clinica Universitaria de Navarra; Servicio de Hematologia | Pamplona, Navarra, 31008, Spain
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia | Salamanca, 37007, Spain
St James University Hospital; Institute of Oncology | Leeds, LS9 7TF, United Kingdom
UCLH - Clinical Trials Pharmacy B&D Centre | London, N7 9NH, United Kingdom
Location Countries

Australia

Belgium

Denmark

Italy

Korea, Republic of

Spain

United Kingdom

Verification Date

October 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Part I: Dose Escalation

Type: Experimental

Description: Participants will receive RO7425781 as intravenous (IV) and/or subcutaneous (SC) infusion in a step-up dosing fashion.

Label: Part II: Dose Expansion

Type: Experimental

Description: Dose Expansion cohorts with IV and/or SC administration will be initiated at the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) determined from Part I: Dose Escalation.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Sequential Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov