MagnetisMM-4: Umbrella Study of Elranatamab (PF-06863135) in Combination With Anti-Cancer Treatments in Multiple Myeloma

Phase 2Active Not RecruitingNCT05090566

Pfizer34 enrolled

Overview

The purpose of this study is to determine the Recommended Phase 2 Dose and clinical benefit of elranatamab in combination with other anti-cancer therapies in participants with multiple myeloma.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

Elranatamab + NirogacestatDRUG

BCMA-CD3 bispecific antibody + gamma secretase inhibitor

Elranatamab + lenalidomide + dexamethasoneDRUG

BCMA-CD3 bispecific antibody + immunomodulatory

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Relapsed/refractory multiple myeloma with at least 3 prior lines of therapy * Refractory to at least one IMiD, one proteasome inhibitor, and one anti-CD38 antibody * Measurable disease defined by at least one of the following: 1. Serum M-protein \>/= 0.5 g/dL by SPEP 2. Urinary M-protein excretion \>/= 200 mg/24 hours by UPEP 3. Serum immunoglobulin FLC \>/= 10 mg/dL (\>/= 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio * ECOG performance status 0 -1 * Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade \</= 1 Exclusion Criteria: * Active plasma cell leukemia * Amyloidosis * Stem cell transplant with 12 weeks prior to enrollment, or active GVHD * POEMS syndrome * Any active uncontrolled bacterial, fungal, or viral infection * Impaired cardiovascular function or clinically significant cardiovascular diseases within 6 months prior to enrollment * Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study treatment (whichever is longer) * Sub-Study A Only: Previous treatment with BCMA bispecific antibody * Sub-Study B Only: Previous treatment with BCMA directed therapy

Locations (25)

Outcomes

Primary Outcomes

Sub-Study A Phase 1: Dose Limiting Toxicity

Number of participants with Dose Limiting Toxicity

Time frame: approximately 35 days

Sub-Study A Phase 2: Objective Response Rate

Objective response rate (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study B Phase 1 Escalation: Dose Limiting Toxicity

Number of participants with Dose Limiting Toxicity

Time frame: approximately 42 days

Secondary Outcomes

Sub-Study A Phase 1: Objective Response Rate

Objective response rate (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study A Phase 1 and Phase 2: Complete Response Rate

Complete response rate (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study A Phase 1 and Phase 2: Time to Response

Time to response (IMWG criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study A Phase 1 and 2: Duration of Response

Duration of response (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study A Phase 1 and Phase 2: Duration of Complete Response

Duration of complete response (IMWG response criteria)

Data from ClinicalTrials.gov

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Banner Gateway Medical Center

Gilbert, Arizona, United States

Banner Gateway Medical Pavilion

Gilbert, Arizona, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Banner Health d.b.a. Banner MD Anderson Cancer Center

Phoenix, Arizona, United States

Beverly Hills Cancer Center

Beverly Hills, California, United States

Clinical Research Advisors

Encino, California, United States

Clinical Research Advisors

Los Angeles, California, United States

Cedars Sinai Medical Center Oncology IDS Pharmacy Attn:Suwicha Limvorasak ,PharmaD

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute (SOCCI)

Los Angeles, California, United States

...and 15 more locations

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study A Phase 1 and Phase 2: Progression Free Survival

Progression free survival (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study A Phase 1 and Phase 2: Overall Survival

Overall survival

Time frame: assessed for approximately 2 years

Sub-Study A Phase 1 and Phase 2: Minimal Residual Disease Negativity Rate

Minimal residual disease negativity rate (IMWG response criteria)

Time frame: assessed approximately every 12 months (for approximately 2 years)

Sub-Study A Phase 1 and Phase 2: Frequency of Treatment-Emergent Adverse Events

Type and severity per NCI CTCAE v5 (CRS and ICANS assessed per ASTCT criteria)

Time frame: assessed for approximately 2 years

Sub-Study A Phase 1 and Phase 2: Frequency of Laboratory Abnormalities

Type and severity per NCI CTCAE v5

Time frame: assessed every cycle (each cycle approximately 28 days)

Sub-Study A Phase 1 and Phase 2: Immunogenicity of elranatamab in combination with nirogacestat

Anti-drug antibodies and neutralizing antibodies against elranatamab

Time frame: assessed approximately every 1 to 3 cycles (each cycle approximately 28 days)

Sub-Study A Phase 1 and Phase 2: Concentrations of elranatamab and/or nirogacestat

Pre-dose and post-dose concentrations of elranatamab; pre-dose concentrations of nirogacestat

Time frame: assessed approximately every 1 to 3 cycles (each cycle approximately 28 days)

Sub-Study A Phase 1: Maximum Observed Concentration (Cmax) for elranatamab

Cmax for elranatamab administration

Time frame: assessed after first elranatamab dose (approximately 3-7 days)

Sub-Study A Phase 1: Time to Maximum Concentration (Tmax) for elranatamab

Tmax for elranatamab administration

Time frame: assessed after first elranatamab dose (approximately 3-7 days)

Sub-Study A Phase 1: Area Under the Concentration versus Time Curve from Time 0 to the Last Measurable Concentration (AUClast) for elranatamab

AUClast for elranatamab administration

Time frame: assessed after first elranatamab dose (approximately 3-7 days)

Sub-Study B Phase 1 Escalation: Frequency of Treatment-Emergent Adverse Events

Type and severity per NCI CTCAE v5 (CRS and ICANS assessed per ASTCT criteria)

Time frame: assessed for approximately 2 years

Sub-Study B Phase 1 Escalation: Frequency of Laboratory Abnormalities

Type and severity per NCI CTCAE v5

Time frame: assessed every cycle (each cycle approximately 28 days)

Sub-Study B Phase 1 Escalation: Objective Response Rate

Objective response rate (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study B Phase 1 Escalation: Complete Response Rate

Complete response rate (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study B Phase 1 Escalation: Time to Response

Time to response (IMWG criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study B Phase 1 Escalation: Duration of Response

Duration of response (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study B Phase 1 Escalation: Duration of Complete Response

Duration of complete response (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study B Phase 1 Escalation: Progression Free Survival

Progression free survival (IMWG response criteria)

Time frame: assessed every 4 weeks (for approximately 2 years)

Sub-Study B Phase 1 Escalation: Overall Survival

Overall survival

Time frame: assessed for approximately 2 years

Sub-Study B Phase 1 Escalation: Minimal Residual Disease Negativity Rate

Minimal residual disease negativity ratio (IMWG response criteria)

Time frame: assessed approximately every 12 months (for approximately 2 years)

Sub-Study B Phase 1 Escalation: Immunogenicity of elranatamab in combination with lenalidomide

Anti-drug antibodies and neutralizing antibodies against elranatamab

Time frame: assessed approximately every 1 to 3 cycles (each cycle approximately 28 days)

Sub-Study B Phase 1 Escalation: Concentrations of elranatamab and/or lenalidomide

Pre-dose and post-dose concentrations of elranatamab, pre-dose concentrations of lenalidomide

Time frame: assessed approximately every 1 to 3 cycles (each cycle approximately 28 days)

Sub-Study B Phase 1 Escalation: Maximum Observed Concentrations (Cmax) for elranatamab

Cmax for elranatamab administration

Time frame: assessed after first elranatamab dose (approximately 3-7 days)

Sub-Study B Phase 1 Escalation: Time to Maximum Concentration (Tmax) for elranatamab

Tmax for elranatamab administration

Time frame: assessed after first elranatamab dose (approximately 3-7 days)

Sub-Study B Phase 1 Escalation: Area Under the Concentration versus Time Curve from Time 0 to the Last Measurable Concentration (AUClast) for elranatamab

AUClast for elranatamab administration

Time frame: assessed after first elranatamab dose (approximately 3-7 days)