A Study of Elranatamab (PF-06863135) in Chinese Participants With Refractory Multiple Myeloma.

Study Overview
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Brief Summary
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The purpose of this study is to understand the study medicine (called Elranatamab, or PF-06863135) as potential treatment for refractory multiple myeloma. Multiple myeloma is a form of cancer in the bone that forces healthy blood cells to go out. Sometimes, multiple myeloma does not respond to current therapy or quickly progresses, and this is called refractory multiple myeloma. Elranatamab is a study medicine that target multiple myeloma and activates the human body to fight against this disease. We are seeking Chinese participants to take part in this study. The study will be 2 parts, called part 1b and part 2. In part 1b, participants will receive Elranatamab at 2 steps priming and full dose as a sc (subcutaneous injection) therapy. We will monitor participants' safety and reactions to the study medicine. This will help us understand the dosage of Elranatamab to be used safely. In part 2 of the study, participants will receive Elranatamab and their multiple myeloma growth will be monitored. This will help us understand if Elranatamab, when used alone, may be a therapy for refractory multiple myeloma. Participants in this part of the study are expected to take part for about 2 years.

Official Title
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A PHASE 1B/2, OPEN-LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF ELRANATAMAB (PF-06863135) IN CHINESE PARTICIPANTS WITH MULTIPLE MYELOMA WHO ARE REFRACTORY TO AT LEAST ONE PROTEASOME INHIBITOR, ONE IMMUNOMODULATORY DRUG AND ONE ANTI-CD38 ANTIBODY (TRIPLE-CLASS REFRACTORY MM)

Conditions
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Elranatamab, Myeloma, Multiple Myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma, PF-06863135, BCMA, Bispecific, Bispecific Antibody, BCMA-CD3 Bispecific, MagnetisMM-8

Intervention / Treatment
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* Drug: Elranatamab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple myeloma (IMWG criteria, Rajkumar et al, 2014) Measurable disease, as defined by at least 1 of the following: Serum M-protein >0.5 g/dL Urinary M-protein excretion >200 mg/24 hours Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio Refractory to at least one IMiD Refractory to at least one PI Refractory to at least one anti-CD38 antibody Relapsed/refractory to last anti-myeloma regimen ECOG performance status ≤2 Adequate BM function characterized by the following: Absolute neutrophil count ≥1.0 × 10^9/L Platelets ≥ 25 × 10^9/L Hemoglobin ≥8 g/dL Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 Not pregnant and willing to use contraception Exclusion Criteria: Smoldering multiple myeloma Active Plasma cell leukemia Amyloidosis POEMS syndrome Stem cell transplant or active GVHD within 12 weeks prior to enrollment. Previous treatment with an anti-BCMA directed therapy Impaired cardiovascular function or clinically significant cardiovascular diseases Ongoing Grade ≥2 peripheral sensory or motor neuropathy. History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy. Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elranatamab<br>BCMA-CD3 bispecific antibody | Drug: Elranatamab<br>* BCMA-CD3 bispecific antibody<br>* Other names: PF-06863135;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Number of participants with dose-limiting toxicities (DLT) | Number of participants with DLTs | Up to 4 weeks | 
| Phase 2: Objective response rate | Objective response rate (IMWG response criteria) | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response | Duration of response (IMWG response criteria) | Up to approximately 2 years | 
| Cumulative complete response rate | Cumulative complete response rate (IMWG response criteria) | Up to approximately 2 years | 
| Duration of cumulative complete response | Duration of cumulative complete response (IMWG response criteria) | Up to approximately 2 years | 
| Progression free survival | Progression free survival (IMWG response criteria) | Up to approximately 2 years | 
| Overall survival (OS) |  | Up to approximately 2 years | 
| Time to response (TTR) | Time to response (IMWG response criteria) | Up to approximately 2 years | 
| Minimal residual disease negativity rate | Minimal residual disease negativity rate (IMWG response criteria) | Up to approximately 2 years | 
| Frequency of treatment-emergent adverse events | Type and severity (including severity per NCI CTCAE v5) | Up to approximately 2 years | 
| Frequency of laboratory abnormalities | Complete blood count and serum chemistry; type and severity of abnormalities (severity per NCI CTCAE v5) | Up to approximately 2 years | 
| Serum Concentration of Elranatamab (PF-06863135) | Serum concentrations of Elranatamab (PF-06863135) will be reported. | Up to approximately 2 years | 
| Immunogenicity of elranatamab (PF-06863135) | Immunogenicity of elranatamab (anti-drug antibodies against elranatamab) | Up to approximately 2 years | 
| Change from Baseline in Patient-Reported Outcomes as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30) | The QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. | Up to approximately 2 years | 
| Change from Baseline in Patient-Reported Outcomes as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire myeloma-specific module (EORTC QLQ-MY20) | The EORTC MY20 is a myeloma-specific module to assess quality of life in patients with multiple myeloma. It contains 20 items which can be grouped into a disease symptom subscale (6 items), side effects of treatment subscale (10 items), body image (1 item) and future perspective subscale (3 items) | Up to approximately 2 years | 
| Change from Baseline in Patient-Reported Outcomes as Assessed by EuroQol Five Dimension Questionnaire (EQ-5D) | The EQ-5D is a 6-item patient-completed questionnaire designed to assess health status in terms of a single index value or utility score. There are 2 components, a Health State Profile which has individuals rate their level of problems in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a VAS in which patients rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). | Up to approximately 2 years | 
| Change from Baseline in Patient-Reported Outcomes as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy Questionnaire (EORTC QLQ CIPN20) | The EORTC QLQ CIPN20 is a module developed to assess chemotherapy-induced peripheral neuropathy. It contains 20 items which can be grouped into a sensory subscale (9 items), motor subscale (8 items) and autonomic subscale (3 items). | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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