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

• ClinicalTrials.gov Identifier: NCT04557150
• Recruitment Status: Recruiting
• First Posted: September 21, 2020
• Last Update Posted: May 17, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: RO7425781	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 11, 2020
• Estimated Primary Completion Date: July 13, 2022
• Estimated Study Completion Date: July 13, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part I: Dose Escalation; Participants will receive RO7425781 as intravenous (IV) infusion and/or subcutaneous (SC) injection in a step-up dosing fashion.	Drug: RO7425781; RO7425781 will be administered via IV/SC administration. 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.
Experimental: Part II: Dose Expansion; 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.	Drug: RO7425781; RO7425781 will be administered via IV/SC administration. 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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 69 weeks ]
2. Percentage of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 69 weeks ]

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Up to 69 weeks ]
2. Duration of Response (DOR) [ Time Frame: Up to 69 weeks ]
3. Progression-Free Survival (PFS) [ Time Frame: Up to 69 weeks ]
4. Overall Survival (OS) [ Time Frame: Up to 69 weeks ]
5. Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7425781 [ Time Frame: Up to 69 weeks ]
6. Maximum concentration (Cmax) of RO7425781 [ Time Frame: Up to 69 weeks ]
7. Time of Maximum concentration (Tmax) of RO7425781 [ Time Frame: Up to 69 weeks ]
8. Minimum concentration (Cmin) of RO7425781 [ Time Frame: Up to 69 weeks ]
9. SC Bioavailability (F) of RO7425781 [ Time Frame: Up to 69 weeks ]
10. Apparent Clearance (CL/F) of RO7425781 [ Time Frame: Up to 69 weeks ]
11. Volume of distribution at steady state (Vss) of RO7425781 (IV only) [ Time Frame: Up to 69 weeks ]
12. Area under the curve (AUC) at various time intervals of RO7425781 [ Time Frame: Up to 69 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 2 weeks before first RO7425781 administration.
• Prior treatment with systemic immunotherapeutic agents within 2 weeks before first RO7425781 administration.
• 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 2 weeks except for alkylating agents (e.g., melphalan) within 28 days, prior to first RO7425781 administration. Limited field palliative radiotherapy for bone pain or for soft tissue lesions is allowed.
• Autologous or allogeneic stem cell transplantation (SCT) within 100 days prior to first RO7425781 administration 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.

Contacts and Locations

Contacts

Contact: Reference Study ID Number: BP42233 https://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

Locations

Australia, Victoria

Peter MacCallum Cancer Center; Recruiting

East Melbourne, Victoria, Australia, 3002

Belgium

UZ Gent; Recruiting

Gent, Belgium, 9000

Denmark

Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT; Recruiting

København Ø, Denmark, 2100

France

CHRU Lille - Hôpital Claude Huriez; Service des Maladies du Sang; Active, not recruiting

Lille, France, 59037

CHU NANTES - Hôtel Dieu; Service d'Hematologie Clinique; Recruiting

Nantes, France, 44093

Hopital De Haut Leveque; Hematologie Clinique; Recruiting

Pessac, France, 33604

Italy

IRCCS Istituto Nazionale dei Tumori di Napoli - Pascale Ematologia Oncologica; Active, not recruiting

Napoli, Campania, Italy, 80131

Fond. IRCCS Istituto Nazionale Tumori; S. C. Ematologia; Active, not recruiting

Milano, Lombardia, Italy, 20133

Instituto Clinico Humanitas; Med Onc & Hemat; Active, not recruiting

Rozzano, Lombardia, Italy, 20089

Korea, Republic of

Seoul National University Hospital; Recruiting

Seoul, Korea, Republic of, 03080

Asan Medical Center; Withdrawn

Seoul, Korea, Republic of, 05505

Spain

Hospital Universitario Marques de Valdecilla; Servicio de Hematologia; Active, not recruiting

Santander, Cantabria, Spain, 39008

Clinica Universitaria de Navarra; Servicio de Hematologia; Recruiting

Pamplona, Navarra, Spain, 31008

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia; Recruiting

Salamanca, Spain, 37007

United Kingdom

University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility; Recruiting

London, United Kingdom, W1T 7HA

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04557150
• Other Study ID Numbers: BP42233; 2020-002012-46 ( EudraCT Number )
• First Posted: September 21, 2020
• Last Update Posted: May 17, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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).

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

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases