Clinical trial NCT05228470: A Study of Elranatamab (PF-06863135) in Chinese Participants With Refractory Multiple Myeloma.
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Elranatamab
Myeloma
Multiple Myeloma
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
PF-06863135
BCMA
Bispecific
Bispecific Antibody
BCMA-CD3 Bispecific
MagnetisMM-8
Keywords: 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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-02-08
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. Absolute neutrophil count ≥1.0 × 10\^9/L
  2. Platelets ≥ 25 × 10\^9/L
  3. 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)

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: Cycle 1 (28 days)
measure: Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (approximately up to 16 months)
Secondary outcomes:
measure: Duration of Response (DOR) as Per IMWG Criteria by BICR
timeFrame: From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months)
measure: Duration of Response (DOR) as Per IMWG Criteria by Investigator Assessment
timeFrame: From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months)
measure: Complete Response Rate (CRR) as Per IMWG Criteria by BICR
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 37 months)
measure: Complete Response Rate (CRR) as Per IMWG Criteria by Investigator Assessment
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 37 months)
measure: Objective Response Rate (ORR) as Per IMWG Criteria by Investigator Assessment
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 37 months)
measure: Duration of Complete Response (DOCR) as Per IMWG Criteria by BICR
timeFrame: From first documentation of sCR/CR subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months)
measure: Duration of Complete Response (DOCR) as Per IMWG Criteria by Investigator Assessment
timeFrame: From the first documentation of sCR/CR, until confirmed PD per IMWG criteria, or death due to any cause, whichever occurred first (up to approximately 37 months)
measure: Progression Free Survival (PFS) as Per IMWG Criteria by BICR
timeFrame: From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months)
measure: Progression Free Survival (PFS) as Per IMWG Criteria by Investigator Assessment
timeFrame: From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months)
measure: Overall Survival (OS)
timeFrame: From the date of first dose until death due to any cause. Participants not known to have died were censored on the date of last known alive (up to approximately 37 months)
measure: Time-to-Response (TTR) as Per IMWG Criteria by BICR
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurs first (approximately up to 16 months)
measure: Time-to-Response (TTR) as Per IMWG Criteria by Investigator Assessment
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurs first (up to approximately 37 months)
measure: Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria
timeFrame: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 37 months)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE), Serious TEAEs, Treatment Related TEAEs, Serious Treatment Related TEAEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
timeFrame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 37 months)
measure: Number of Participants With Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria
timeFrame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 37 months)
measure: Number of Participants With Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Graded According to ASTCT Criteria
timeFrame: From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 37 months)
measure: Maximum Serum Concentration (Cmax) of Free Elranatamab
timeFrame: Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days)
measure: Time To Maximum Serum Concentration (Tmax) of Free Elranatamab
timeFrame: Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days)
measure: Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab
timeFrame: Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days)
measure: Serum Concentration of Free Elranatamab
timeFrame: Up to 37 months
measure: Percentage of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) Against Elranatamab
timeFrame: From the date of first dose up to 37 months
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life of Cancer Participants Core Module (EORTC QLQ-C30)
timeFrame: Baseline and up to 37 months
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Myeloma-Specific Module (EORTC QLQ-MY20)
timeFrame: Baseline and up to 37 months
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ CIPN20)
timeFrame: Baseline and up to 37 months
measure: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Index Score and in EQ-5D Visual Analogue Score (VAS) (EQ-VAS)
timeFrame: Baseline and up to 37 months
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Second People's Hosptial
state: Guangdong
city: Harbin
country: China
facility: Harbin First Hospital
state: Heilongjiang
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine, Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: Beijing Gaobo Boren Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Tianjin
country: China
facility: Hematology Hospital, Chinese Academy of Medical Sciences
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: