Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT03486067
• Recruitment Status: Active, not recruiting
• First Posted: April 3, 2018
• Last Update Posted: November 9, 2022
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: March 21, 2018
• First Posted Date: April 3, 2018
• Last Update Posted Date: November 9, 2022
• Actual Study Start Date: April 3, 2018
• Estimated Primary Completion Date: July 26, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 22, 2022)

• Adverse Events (AEs) [ Time Frame: Up to 60 months ]
  Number of participants with Adverse Events
• Dose Limiting Toxicity (DLT) [ Time Frame: Up to 60 months ]
  Is defined as any of the toxicities occurring within the DLT assessment window (Cycle 1, Days 1 to 28) except those that are clearly and incontrovertibly due to extraneous causes.
• Non-Tolerated Dose (NTD) [ Time Frame: Up to 60 months ]
  Is defined as a dose level at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in the DLT window.
• Maximum Tolerated Dose (MTD) [ Time Frame: Up to 60 months ]
  Is defined as the last dose cohort below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during the DLT window.

Original Primary Outcome Measures (submitted: March 30, 2018)

• Adverse Events (AEs) [ Time Frame: Up to 48 months ]
  Number of participants with Adverse Events
• Dose Limiting Toxicity (DLT) [ Time Frame: Up to 48 months ]
  Is defined as any of the toxicities occurring within the DLT assessment window (Cycle 1, Days 1 to 28) except those that are clearly and incontrovertibly due to extraneous causes.
• Non-Tolerated Dose (NTD) [ Time Frame: Up to 48 months ]
  Is defined as a dose level at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in the DLT window.
• Maximum Tolerated Dose (MTD) [ Time Frame: Up to 48 months ]
  Is defined as the last dose cohort below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during the DLT window.

Current Secondary Outcome Measures (submitted: April 22, 2022)

• Overall Response Rate (ORR) [ Time Frame: Up to 60 months ]
  Is defined as the proportion of subjects who achieve a partial response or better (eg, PR, VGPR, CR or sCR), according to International Myeloma Working Group (IMWG) response criteria.
• Time to Response [ Time Frame: Up to 60 months ]
  Is defined as the time from the first CC-93269 dose date to the date of first documented response (PR or better).
• Duration of Response [ Time Frame: Up to 60 months ]
  Is defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.
• Progression Free Survival [ Time Frame: Up to 60 months ]
  Is defined as the time from the first dose of CC-93269 to progressive disease or death from any cause, whichever occurs first.
• Overall Survival [ Time Frame: Up to 60 months ]
  Is defined as the time from the first dose of CC-93269 to death from any cause.
• Pharmacokinetics - Cmax [ Time Frame: Up to 60 months ]
  Maximum serum concentration of drug
• Pharmacokinetics - Cmin [ Time Frame: Up to 60 months ]
  Minimum serum concentration of drug
• Pharmacokinetics - AUC [ Time Frame: Up to 60 months ]
  Area under the curve
• Pharmacokinetics - tmax [ Time Frame: Up to 60 months ]
  Time to peak (maximum) serum concentration
• Pharmacokinetics - t1/2 [ Time Frame: Up to 60 months ]
  Terminal Half-life
• Pharmacokinetics - CL [ Time Frame: Up to 60 months ]
  Apparent total body clearance
• Pharmacokinetics - Vss [ Time Frame: Up to 60 months ]
  Volume of distribution at steady-state
• Pharmacokinetics - accumulation index of alnuctamab [ Time Frame: Up to 60 months ]
  Accumulation ratio of drug
• Presence and frequency of anti-drug antibodies (ADA) [ Time Frame: Up to 60 months ]
  Detection of anti-drug antibodies in participants and frequency of anti-drug antibodies
• Evaluate measures of tumor sensitivity/ resistance to CC-93269 [ Time Frame: Up to 60 months ]
  Measurement of tumor and immune factors

Original Secondary Outcome Measures (submitted: March 30, 2018)

• Overall Response Rate (ORR) [ Time Frame: Up to 48 months ]
  Is defined as the proportion of subjects who achieve a partial response or better (eg, PR, VGPR, CR or sCR), according to International Myeloma Working Group (IMWG) response criteria.
• Time to Response [ Time Frame: Up to 48 months ]
  Is defined as the time from the first CC-93269 dose date to the date of first documented response (PR or better).
• Duration of Response [ Time Frame: Up to 48 months ]
  Is defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.
• Progression Free Survival [ Time Frame: Up to 48 months ]
  Is defined as the time from the first dose of CC-93269 to progressive disease or death from any cause, whichever occurs first.
• Overall Survival [ Time Frame: Up to 48 months ]
  Is defined as the time from the first dose of CC-93269 to death from any cause.
• Pharmacokinetics - Cmax [ Time Frame: Up to 48 months ]
  Maximum serum concentration of drug
• Pharmacokinetics - Cmin [ Time Frame: Up to 48 months ]
  Minimum serum concentration of drug
• Pharmacokinetics - AUC [ Time Frame: Up to 48 months ]
  Area under the curve
• Pharmacokinetics - tmax [ Time Frame: Up to 48 months ]
  Time to peak (maximum) serum concentration
• Pharmacokinetics - t1/2 [ Time Frame: Up to 48 months ]
  Terminal Half-life
• Pharmacokinetics - CL [ Time Frame: Up to 48 months ]
  Apparent total body clearance
• Pharmacokinetics - Vss [ Time Frame: Up to 48 months ]
  Volume of distribution at steady-state
• Pharmacokinetics - accumulation index of CC-93269 [ Time Frame: Up to 48 months ]
  Accumulation ratio of drug
• Presence and frequency of anti-drug antibodies (ADA) [ Time Frame: Up to 48 months ]
  Detection of anti-drug antibodies in participants and frequency of anti-drug antibodies
• Evaluate measures of tumor sensitivity/ resistance to CC-93269 [ Time Frame: Up to 48 months ]
  Measurement of tumor and immune factors

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

Descriptive Information

• Brief Title: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma
• Official Title: A Phase 1, Open-label, Dose Finding Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Subjects With Relapsed and Refractory Multiple Myeloma
• Brief Summary: Study CC-93269-MM-001 is an open-label, Phase 1, dose escalation (Part A and C) and expansion (Parts B and D), first-in-human clinical study of CC-93269 in subjects with relapsed and refractory multiple myeloma.
• Detailed Description: The dose escalation parts (Part A with CC-93269 administered intravenous (IV) and Part C subcutaneous (SC)) of the study will evaluate the safety and tolerability of escalating doses of CC-93269, administered IV or SC, to determine the maximum tolerated dose (MTD) and non-tolerated dose (NTD) of CC-93269. The expansion parts (Part B and D) will further evaluate the safety and efficacy of CC-93269 administered IV or SC at or below the MTD in selected expansion cohorts of up to approximately 20 evaluable subjects each in order to determine the Recommended Phase 2 dose (RP2D).One or more dosing regimens may be selected for cohort expansion. All treatments will be administered in 28-day cycles for up to 2 years or extended up to 5 years for subjects maintaining clinical benefit at the discretion of the Safety Review Committee, until confirmed disease progression, unacceptable toxicity, or subject/investigator decision to withdraw.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

Drug: CC-93269

Specified dose on specified days

Other Name: Alnuctamab

Study Arms

Experimental: Administration of CC-93269

Intervention: Drug: CC-93269

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 22, 2022): 220
• Original Estimated Enrollment (submitted: March 30, 2018): 120
• Estimated Study Completion Date: August 30, 2027
• Estimated Primary Completion Date: July 26, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• History of multiple myeloma with relapsed and refractory disease
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Must have measurable disease as determined by the central laboratory

Exclusion Criteria:

• Symptomatic central nervous system involvement of multiple myeloma
• Prior autologous stem cell transplant ≤ 3 months prior
• Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 12 months prior
• History of concurrent second cancers requiring active, ongoing systemic treatment

Other protocol-defined inclusion/exclusion criteria apply

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: Germany, Italy, Spain, Sweden, United States

Administrative Information

• NCT Number: NCT03486067
• Other Study ID Numbers: CC-93269-MM-001; U1111-1210-6325 ( Registry Identifier: WHO ); 2017-003448-19 ( 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: Not Provided
• Current Responsible Party: Celgene
• Original Responsible Party: Same as current
• Current Study Sponsor: Celgene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Celgene
• Verification Date: November 2022