Clinical trial NCT04557150: A Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of Forimtamig in Participants With Relapsed or Refractory Multiple Myeloma (r/r MM)
Official title: An Open-Label, Multicenter, Phase I Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of Forimtamig (RO7425781) in Participants With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-09-21
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human, open-label, uncontrolled, multi-center, monotherapy, dose-escalation and dose expansion study. Forimtamig 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 forimtamig (Part 1) and a randomized dose expansion of forimtamig (Part 2).


Eligibility criteria: Inclusion Criteria:

* Previously diagnosed with Multiple Myeloma (MM) based on standard criteria.
* Dose Escalation Phase and Dose Expansion 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.
* 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 last dose of study drug.
* Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate for MM treatment within 2 weeks before first forimtamig administration.
* Prior treatment with systemic immunotherapeutic agents within 2 weeks before first forimtamig 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, prior to first forimtamig 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 forimtamig infusion and/or signs of chronic graft versus host disease or ongoing immunosuppressive medication.
* Prior solid organ transplantation.
* Active auto-immune disease or flare within 6 months prior to start of study treatment
* 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.

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 104 weeks
measure: Percentage of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 Day 1 up to Cycle 1 Day 35
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 104 weeks
measure: Duration of Response (DOR)
timeFrame: Up to 104 weeks
measure: Progression-Free Survival (PFS)
timeFrame: Up to 104 weeks
measure: Overall Survival (OS)
timeFrame: Up to 104 weeks
measure: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Forimtamig
timeFrame: Up to 104 weeks
measure: Maximum Concentration (Cmax) of Forimtamig
timeFrame: Up to 104 weeks
measure: Time of Maximum Concentration (Tmax) of Forimtamig
timeFrame: Up to 104 weeks
measure: Minimum Concentration (Cmin) of Forimtamig
timeFrame: Up to 104 weeks
measure: SC Bioavailability (F) of Forimtamig
timeFrame: Up to 104 weeks
measure: Apparent Clearance (CL/F) of Forimtamig
timeFrame: Up to 104 weeks
measure: Volume of Distribution at Steady State (Vss) of Forimtamig (IV only)
timeFrame: Up to 104 weeks
measure: Area Under the Curve (AUC) at Various Time Intervals of Forimtamig
timeFrame: Up to 104 weeks
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Gent
country: Belgium
facility: UZ Gent
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Lille
country: France
facility: CHRU Lille - Hôpital Claude Huriez
city: Nantes
country: France
facility: CHU NANTES - Hôtel Dieu
city: Pessac
country: France
facility: Hopital De Haut Leveque
city: Napoli
country: Italy
facility: IRCCS Istituto Nazionale dei Tumori di Napoli - Pascale Ematologia Oncologica
state: Campania
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi
state: Emilia-Romagna
city: Milano
country: Italy
facility: Fond. IRCCS Istituto Nazionale Tumori
state: Lombardia
city: Rozzano
country: Italy
facility: Instituto Clinico Humanitas
state: Lombardia
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research - Auckland
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: