Study of Novel Regimens in Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a multicenter, open-label, phase I/II clinical study, to assess the safety, tolerability, antitumor activity, pharmacokinetics and pharmacodynamics of EOS884448 (also known as EOS-448 or GSK4428859A), alone or in combination with iberdomide with and without dexamethasone in participants with relapsed/refractory multiple myeloma (RRMM).

Official Title
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Study of EOS884448 Alone, and in Combination With Iberdomide With or Without Dexamethasone, in Participants With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: EOS884448
* Drug: Iberdomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants must have a documented diagnosis of relapse/refractory Multiple Myeloma and have measurable disease as defined per IMWG criteria. All participants must have received at least 3 prior lines of MM therapy with IMiD, PI and Anti-CD-38, and progressed on their last therapy (prior BCMA targeted therapy allowed). All participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0,1or 2. All participants must have adequate organ function. Females of childbearing potential (FCBP) or male participant must agree to follow contraception requirements. Exclusion Criteria: All participants with non-secretory MM All participants with known auto-immune disease All participants with history of life-threatening toxicity related to prior immune therapy. All participants with active graft versus host disease after allogeneic stem cell transplantation. All participants with active, unstable cardiovascular function. All participants with active infection requiring systemic therapy. All participants with hypersensitivity to any of the treatments. All participants with any active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of study treatment.

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Participants will receive EOS884448<br>EOS884448 will be administered | Drug: EOS884448<br>* EOS884448 will be administered in arm A,B and C<br>* Other names: EOS-448, GSK4428859A;|
| Experimental: B: Participants will receive EOS884448 and iberdomide<br>EOS884448 and iberdomide will be administered | Drug: EOS884448<br>* EOS884448 will be administered in arm A,B and C<br>* Other names: EOS-448, GSK4428859A;Drug: Iberdomide<br>* Iberdomide will be administered in arm B and C<br>* Other names: CC-220;|
| Experimental: C: Participants will receive EOS884448, iberdomide and dexamethasone<br>EOS884448, iberdomide and dexamethasone will be administered | Drug: EOS884448<br>* EOS884448 will be administered in arm A,B and C<br>* Other names: EOS-448, GSK4428859A;Drug: Iberdomide<br>* Iberdomide will be administered in arm B and C<br>* Other names: CC-220;Drug: Dexamethasone<br>* Dexamethasone will be administered in arm C<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with any adverse events (AEs) and serious adverse events (SAEs) |  | From first study treatment administration up to 120 days after the last dose | 
| Number of participants with dose limiting toxicity (DLT) |  | From first study treatment administration up to 120 days after the last dose | 
| Recommended Phase 2 dose (RP2D) of EOS884448 alone or in combinations with iberdomide with or without dexamethasone in participants with relapse/refractory multiple myeloma |  | up to 2 years | 
| Number of participants with overall response (partial or better) as determined by IMWG criteria |  | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free-survival (PFS) |  | Until disease progression or death - Approximately 24 months | 
| Duration of Response (DOR) |  | Until disease progression or death - Approximately 24 months | 
| Time to Response (TTR) |  | Approximately 48 weeks | 
| Maximum concentration (Cmax) of EOS884448 at each dose level |  | Approximately 48 weeks | 
| Percentage of participants with anti-drug antibodies to EOS884448 |  | Approximately 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, EOS884448, GSK4428859A, TIGIT, Anti-TIGIT, iberdomide, CELMoD, CC-220, EOS-448