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

• ClinicalTrials.gov Identifier: NCT03269136
• Recruitment Status: Active, not recruiting
• First Posted: August 31, 2017
• Last Update Posted: July 11, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: August 16, 2017
• First Posted Date: August 31, 2017
• Last Update Posted Date: July 11, 2022
• Actual Study Start Date: November 29, 2017
• Estimated Primary Completion Date: April 28, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 13, 2021)

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

Original Primary Outcome Measures (submitted: August 29, 2017)

• Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: 21 days ]
  First cycle DLTs during dose escalation in order to determine the maximum tolerated dose (MTD).
• Dose Expansion: To assess clinical efficacy at RP2D. [ Time Frame: Baseline, 1, 3, 9 and every 6 months thereafter until disease progression, unacceptable toxicity or end of study (average of 2 years). ]
  Overall response rate
• Dose Expansion: To assess clinical efficacy at RP2D. [ Time Frame: Baseline, 1, 3, 9 and every 6 months thereafter until disease progression, unacceptable toxicity or end of study (average of 2 years). ]
  Duration of response.

Current Secondary Outcome Measures (submitted: April 13, 2021)

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

Original Secondary Outcome Measures (submitted: August 29, 2017)

• To evaluate incidence of treatment emergent adverse events and laboratory abnormalities [ Time Frame: From baseline until 1 month after end of treatment ]
  Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities
• To evaluate anti myeloma activity. [ Time Frame: Baseline, 1, 3, 9 and every 6 months thereafter until disease progression, unacceptable toxicity or end of study (average of 2 years). ]
  Overall response rate
• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: From baseline and scheduled timepoints post dose through study completion, on average 2 years ]
  Cmax will be calculated for PF-06863135.
• Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) [ Time Frame: From baseline and scheduled timepoints post dose through study completion, on average 2 years ]
  Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose of PF-06863135 will be calculated.
• Incidence of anti-drug antibodies [ Time Frame: From baseline and scheduled timepoints post dose through study completion, on average 2 years ]
  Number of participants with the presence of anti-PF-06863135 antibodies.
• Impact of PF 06863135 on systemic soluble immune factors. [ Time Frame: From baseline and scheduled timepoints post dose through study completion, on average 2 years ]
  Pre and post dose quantification of soluble cytokines in serum.
• To evaluate anti myeloma activity. [ Time Frame: Baseline, 1, 3, 9 and every 6 months thereafter until disease progression, unacceptable toxicity or end of study (average of 2 years). ]
  Time to event endpoints including duration of response.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma
• Official Title: 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)
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: PF-06863135 monotherapy IV or SC
  PF-06863135 will be administered intravenously or subcutaneously.
  Other Name: BCMA-CD3 bispecific antibody
• Drug: PF-06863135 + dexamethasone
  PF-06863135 will be administered intravenously or subcutaneously and dexamethasone orally.
  Other Name: BCMA-CD3 bispecific antibody + dexamethasone
• Drug: PF-06863135 + lenalidomide
  PF-06863135 will be administered intravenously or subcutaneously and lenalidomide orally
  Other Name: BCMA-CD3 bispecific antibody + lenalidomide
• Drug: PF-06863135 + pomalidomide
  PF-06863135 will be administered intravenously or subcutaneously and pomalidomide orally
  Other Name: BCMA-CD3 bispecific antibody + pomalidomide

Study Arms

• Experimental: PF-06863135
  BCMA-CD3 bispecific antibody
  Intervention: Drug: PF-06863135 monotherapy IV or SC
• Experimental: PF-06863135 + dexamethasone
  BCMA-CD3 bispecific antibody + dexamethasone
  Intervention: Drug: PF-06863135 + dexamethasone
• Experimental: PF-06863135 + lenalidomide
  BCMA-CD3 bispecific antibody + lenalidomide
  Intervention: Drug: PF-06863135 + lenalidomide
• Experimental: PF-06863135 + pomalidomide
  BCMA-CD3 bispecific antibody + pomalidomide
  Intervention: Drug: PF-06863135 + pomalidomide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 7, 2022): 103
• Original Estimated Enrollment (submitted: August 29, 2017): 140
• Estimated Study Completion Date: April 28, 2023
• Estimated Primary Completion Date: April 28, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States
• Removed Location Countries: Greece

Administrative Information

• NCT Number: NCT03269136
• Other Study ID Numbers: C1071001; 2019-000822-24 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: July 2022