A Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma

NCT06055075 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: BP434372023-503689-21-002023
• Study Type: interventional
• Target: 21
• Locations: 6 countries
• Sites: 8

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and preliminary anti-tumor activity of forimtamig when administered alone or in combination with carfilzomib or daratumumab or other combination partners in participants with relapsed or refractory multiple myeloma (r/r MM). The study consists of two phases: a dose exploration phase and a dose-expansion phase.

Conditions

Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Adverse Effects (AEs)

  AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  From initiation of study treatment up to approximately 15.7 months

• Number of Participants With Cytokine Release Syndrome (CRS), With Severity Determined According to American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading

  CRS=supraphysiologic response following administration of any immune therapy that results in activation/engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms may be progressive, including fever at onset, headache, and myalgia and may also include hypotension, capillary leak (hypoxia), dyspnea, chest discomfort and end-organ dysfunction. Severity of CRS was determined per ASTCT Consensus Grading Criteria, which categorizes CRS into 5 grades- Grade 1: Fever (≥38◦Celsius), with/without constitutional symptoms, in absence of hypotension \& hypoxia; Grade 2: Fever with hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen; Grade 3: Fever with hypotension requiring one vasopressor, with/without vasopressin, and/or hypoxia requiring high-flow oxygen; Grade 4: Fever accompanied by hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring positive-pressure ventilation; Grade 5: death due to CRS.

  From initiation of study treatment up to approximately 15.7 months

• Number of Participants With Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), With Severity Determined According to ASTCT Consensus Grading

  ICANS grade is determined by the most severe event (immune effector cell-associated encephalopathy \[ICE\] score, level of consciousness, seizures, motor findings, raised intracranial pressure \[ICP\]/cerebral edema) not attributed to any other cause. Grade 1=ICE score of 7-9; awakens spontaneously; no seizure/motor findings/elevated ICP/cerebral edema. Grade 2=ICE score of 3-6; awakes voice; no seizure/motor findings/elevated ICP/cerebral edema. Grade 3=ICE score of 0-2; awakes only to tactile stimulus; any clinical seizure focal or generalized that resolves rapidly or nonconvulsive seizure on EEG that resolves with intervention; no motor findings; focal/local edema on neuroimaging.

  From initiation of study treatment up to approximately 15.7 months

• Investigator-assessed Objective Response Rate (ORR) Per International Myeloma Working Group (IMWG) Response Criteria

  ORR=percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG response criteria. CR \& sCR are defined as outlined in endpoint 5 (CRR/sCRR). VGPR=serum \& urine M-protein (UMP) detectable by immunofixation, but not electrophoresis; ≥90% reduction in serum M-protein (SMP) + UMP level \<100 mg/24 hrs; at baseline ≥90% reduction in sum of the maximal perpendicular diameter (SPD) compared with baseline for soft tissue plasmacytoma \& ≥90% decrease in the difference between involved \& uninvolved SFLC levels. PR=≥50% reduction in SMP \& UMP reduction ≥90% or \<200 mg/24hours; if SMP \& UMP not measurable, ≥50% decrease in involved \& uninvolved SFLC difference in place of M-protein criteria; if SMP, UMP \& SFLC assay not unmeasurable, ≥50% reduction in plasma cells required in place of M-protein (baseline BM plasma cell ≥30%); at baseline, a ≥50% reduction in SPD of soft tissue plasmacytomas.

  Up to approximately 15.2 months

• Investigator-assessed Complete Response Rate (CRR) / Stringent Complete Response Rate (sCRR) Per IMWG Response Criteria

  CRR and sCRR were defined as the percentage of participants with CR or sCR, as determined by the investigator per IMWG response criteria. CR was defined as: no evidence of initial monoclonal protein isotype(s) on immunofixation of the serum \& urine; Disappearance of any soft tissue plasmacytomas; \<5% plasma cells in BM \& a normal SFLC ratio of 0.26-1.65. sCR was defined as: CR (defined above); normal SFLC ratio, \& absence of clonal cells in BM by IHC or negative by 2-4 color flow cytometry. CR and sCR are distinct response categories and are evaluated and reported separately in accordance with the defined response criteria i.e., if a response is clinically upgraded from CR to sCR it is not further considered a CR but solely a sCR. Percentages have been rounded off.

  Up to approximately 15.2 months

• Investigator-assessed VGPR Rate or Better Per IMWG Response Criteria

  VGPR rate was defined as the percentage of participants with VGPR as determined by the investigator per IMWG response criteria. VGPR was defined as: serum \& UMP detectable by immunofixation, but not on electrophoresis; or ≥90% reduction in SMP plus UMP level \<100 mg/24 hours; at baseline ≥90% reduction in SPD compared with baseline for soft tissue plasmacytoma \& ≥90% decrease in the difference between involved \& uninvolved SFLC levels. Responses better than VGPR include CR and sCR (as defined in endpoint 5). Percentages have been rounded off.

  Up to approximately 15.2 months

Secondary Outcomes (9)

• Investigator-assessed Progression-free Survival (PFS) Per IMWG Response Criteria

  Up to approximately 15.2 months

• Investigator-assessed Duration of Response (DoR) for Participants Who Achieved PR or Better

  Up to approximately 15.2 months

• Investigator-assessed Time to Response (TTR) Per IMWG Response Criteria

  Up to approximately 15.2 months

• Investigator-assessed Time to Best Response (TTBR) Per IMWG Response Criteria

  Up to approximately 15.2 months

• Investigator-assessed Overall Survival (OS)

  Up to approximately 15.7 months

Study Arms (9)

Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib

EXPERIMENTAL

Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression.

Drug: Forimtamig; Drug: Carfilzomib

Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib

EXPERIMENTAL

Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.

Drug: Forimtamig; Drug: Carfilzomib

Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib

EXPERIMENTAL

Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.

Drug: Forimtamig; Drug: Carfilzomib

Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab

EXPERIMENTAL

Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Drug: Forimtamig; Drug: Daratumumab

Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab

EXPERIMENTAL

Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Drug: Forimtamig; Drug: Daratumumab

Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab

EXPERIMENTAL

Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Drug: Forimtamig; Drug: Daratumumab

Dose Expansion Phase: Forimtamig

EXPERIMENTAL

Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase until disease progression or completion of 12 months of treatment, whichever occurs first.

Drug: Forimtamig

Dose Expansion Phase: Forimtamig + Carfilzomib

EXPERIMENTAL

Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression.

Drug: Forimtamig; Drug: Carfilzomib

Dose Expansion Phase: Forimtamig + Daratumumab

EXPERIMENTAL

Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression.

Drug: Forimtamig; Drug: Daratumumab

Interventions

Forimtamig DRUG

Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.

Dose Expansion Phase: Forimtamig; Dose Expansion Phase: Forimtamig + Carfilzomib; Dose Expansion Phase: Forimtamig + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab

Carfilzomib DRUG

Carfilzomib will be administered via IV infusion in combination with forimtamig.

Dose Expansion Phase: Forimtamig + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib

Daratumumab DRUG

Daratumumab will be administered via SC injection in combination with forimtamig.

Dose Expansion Phase: Forimtamig + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Documented diagnosis of MM according to the IMWG diagnostic criteria
• Evidence of progressive disease based on Investigator's determination of response by IMWG criteria on or after last dosing regimen
• Measurable disease
• AEs from prior anti-cancer therapy resolved to Grade ≤ 1,
• Adequate organ functions

You may not qualify if:

• Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the last dose of study drug
• Plasma cell leukemia with circulating plasma cell count ≥ 5% or \>500/microliter (µL)
• Participants with known amyloidosis
• Participants with myelodysplastic syndrome
• Prior treatment with monoclonal antibody (mAb) and antibody-drug conjugate within 4 weeks or 5 half-lives of the drug, whichever is shorter
• Prior anti-cancer therapy (chemotherapy, small molecule/tyrosine kinase inhibitors, radiotherapy) within 14 days prior to first forimtamig administration
• Prior solid organ transplantation
• Active auto-immune disease or flare within 6 months prior to start of study treatment
• Known or suspected chronic active Epstein-Barr virus (EBV) infection
• Hepatitis B virus (HBV) infection
• Acute or chronic hepatitis C virus (HCV) infection
• Known history of HIV seropositivity
• Live vaccine(s) within one month prior to start of the treatment
• Participants not fully vaccinated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per local recommendations
• Previous refractoriness to carfilzomib

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

Princess Alexandra Hospital Woolloongabba

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Istituto Clinico Humanitas

Rozzano, Lombardy, 20089, Italy

Location

New Zealand Clinical Research - Auckland

Auckland, 1010, New Zealand

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Seoul St Mary's Hospital

Seoul, 06591, South Korea

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

carfilzomib; daratumumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: September 26, 2023
• Study Start: December 8, 2023
• Primary Completion: July 8, 2025
• Study Completion: July 8, 2025
• Last Updated: September 29, 2026
• Results First Posted: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

IT (1); AU (2); ES (1); NZ (1); CA (1); KR (2)