PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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To assess the safety and tolerability at increasing dose levels of PF-06863135 in patients with relapse/ refractory multiple myeloma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Detailed Description
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Study C1071001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-06863135 in adult patients with advanced multiple myeloma who have relapsed from or are refractory to standard therapy. This is a two part study; Part 1 will assess the safety and tolerability of increasing dose levels of PF-06863135 and Part 2 will evaluate safety and anti-myeloma activity of PF-06863135 at the RP2Ds determined in Part 1.

Official Title
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MAGNETISMM-1 A PHASE I, OPEN LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL ACTIVITY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) - CD3 BISPECIFIC ANTIBODY, AS A SINGLE AGENT AND IN COMBINATION WITH IMMUNOMODULATORY AGENTS IN PATIENTS WITH RELAPSED/REFRACTORY ADVANCED MULTIPLE MYELOMA (MM)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: PF-06863135 monotherapy IV or SC
* Drug: PF-06863135 + dexamethasone
* Drug: PF-06863135 + lenalidomide
* Drug: PF-06863135 + pomalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed/refractory multiple myeloma Progressed or are intolerant of established therapies including proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody Performance Status of 0- 1 ( Performance Score 2 is permitted only if due to underlying myeloma) Adequate bone marrow, hematological, kidney and liver function Resolved acute effects of any prior therapy to baseline severity Not pregnant Exclusion Criteria: Recent history of other malignancies History of active autoimmune disorders Any form of primary immunodeficiency Active and clinically significant bacterial, fungal, or viral infection Evidence of active mucosal or internal bleeding History of severe immune-mediated adverse event with prior immunomodulatory treatment Major surgery within 4 weeks of study treatment start Radiation therapy within 2 weeks of study treatment start History of stem cell transplant (autologous or allogeneic) within 100 days prior to study enrollment Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry Less than 30 days since last dose of antibody based therapies or less than 5 half-lives since last dose of previous therapy Requirement for systemic immune suppressive medication except as permitted in the protocol Current requirement for chronic blood product support

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: PF-06863135<br>BCMA-CD3 bispecific antibody | Drug: PF-06863135 monotherapy IV or SC<br>* PF-06863135 will be administered intravenously or subcutaneously.<br>* Other names: BCMA-CD3 bispecific antibody;|
| Experimental: PF-06863135 + dexamethasone<br>BCMA-CD3 bispecific antibody + dexamethasone | Drug: PF-06863135 + dexamethasone<br>* PF-06863135 will be administered intravenously or subcutaneously and dexamethasone orally.<br>* Other names: BCMA-CD3 bispecific antibody + dexamethasone;|
| Experimental: PF-06863135 + lenalidomide<br>BCMA-CD3 bispecific antibody + lenalidomide | Drug: PF-06863135 + lenalidomide<br>* PF-06863135 will be administered intravenously or subcutaneously and lenalidomide orally<br>* Other names: BCMA-CD3 bispecific antibody + lenalidomide;|
| Experimental: PF-06863135 + pomalidomide<br>BCMA-CD3 bispecific antibody + pomalidomide | Drug: PF-06863135 + pomalidomide<br>* PF-06863135 will be administered intravenously or subcutaneously and pomalidomide orally<br>* Other names: BCMA-CD3 bispecific antibody + pomalidomide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) | Number of participants with DLTs | At the end of Cycle 1 (each Cycle is 21 or 28 days) | 
| To evaluate anti-myeloma activity by objective response rate (ORR) in dose expansion | Percentage of participants with Objective Response Rate (ORR) using the international myeloma working group (IMWG) response criteria for multiple myeloma | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 
| To evaluate anti-myeloma activity by duration of response (DOR) in dose expansion | Time from first assessment of partial response or better to last assessment of partial response or better by IMWG criteria | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate incidence of treatment emergent adverse events and laboratory abnormalities | Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 
| To evaluate anti-myeloma activity by objective response rate (ORR) in dose escalation | Percentage of participants with Objective Response Rate (ORR) using the international myeloma working group (IMWG) response criteria for multiple myeloma | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 
| To evaluate anti-myeloma activity by time to event endpoints | Time from start date to date of first documentation of event (response or progression by IMWG criteria or death) | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 
| To evaluate anti-myeloma activity by duration of event endpoints | Time from first assessment of event endpoint (response or stable disease) to last assessment of (response or stable disease) by IMWG criteria | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 
| Impact of treatment on systemic soluble immune factors | Pre and post dose quantification of soluble cytokines in serum. | 9 months on treatment | 
| Maximum plasma concentration (Cmax) of PF-06863135 | Peak concentration of PF-06863135 during first cycle | Cycle 1 Day 1 and Cycle 2 Day 1 (3 to 4 weeks) | 
| Trough serum concentrations of PF-06863135 and dexamethasone | Trough serum concentrations of PF-06863135 and dexamethasone at selected cycles | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 
| Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-06863135 | AUC of PF-06863135 will be calculated at selected cycles | From baseline through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 
| Incidence and titers of anti-drug antibodies and neutralizing antibodies against PF-06863135 | Number of participants with the presence of anti-PF-06863135 antibodies | From baseline and scheduled timepoints post dose through disease progression, patient refusal, unacceptable toxicity or study completion (approximately 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bispecific, BCMA, BCMA- CD3 bispecific, Phase 1, PF-06863135, dexamethasone, lenalidomide, pomalidomide, Multiple Myeloma, relapse/ refractory multiple myeloma, bispecific antibody