Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Subjects With Relapsed and Refractory Multiple Myeloma
Clinicaltrials.gov identifier recruitment status First Posted Last update posted
NCT03486067 Recruiting April 3, 2018 August 11, 2020

study description
Brief Summary

Study CC-93269-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Parts B and C), first-in-human clinical study of CC-93269 in subjects with relapsed and refractory multiple myeloma.

Condition or Disease: Multiple Myeloma
Intervention/treatment: Drug: CC-93269
Phase: Phase 1
Detailed Description

The dose escalation part (Part A) of the study will evaluate the safety and tolerability of
escalating doses of CC-93269, administered intravenously (IV), to determine the MTD and NTD
of both the first dose and subsequent doses of CC-93269. The expansion part (Part B) will
further evaluate the safety and efficacy of CC-93269 administered IV at or below the MTD in
selected expansion cohorts of up to approximately 20 evaluable subjects each in order to
determine the RP2D. CC-93269, administered IV followed by subcutaneously (SC), will also be
evaluated (Part C). 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 until confirmed disease
progression, unacceptable toxicity, or subject/Investigator decision to withdraw.


study design
Study Type: Interventional
Estimated Enrollment : 115 participants
Intervention Model : Single Group Assignment
Masking: None (Open Label) ()
Primary Purpose: Treatment
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.
Actual Study Start Date: April 2018
Estimated Primary Completion Date: October 2023
Estimated Study Completion Date: November 2023

Arms and interventions
Arm Intervention/treatment
Experimental: Administration of CC-93269
CC-93269 by intravenous (IV) infusion or subcutaneous (SC) injection on a 28 day cycle.
Drug: CC-93269
CC-93269
outcome measures
Primary Outcome Measures: 1. Adverse Events (AEs) [ Time Frame: Up to 48 months ]
Number of participants with Adverse Events
2. 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.
3. 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.
4. 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.
Secondary Outcome Measures: 1. Pharmacokinetics - CL [ Time Frame: Up to 48 months ]
Apparent total body clearance
2. Pharmacokinetics - Vss [ Time Frame: Up to 48 months ]
Volume of distribution at steady-state
3. 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.
4. 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).
5. 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.
6. 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.
7. 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.
8. Pharmacokinetics - Cmax [ Time Frame: Up to 48 months ]
Maximum serum concentration of drug
9. Pharmacokinetics - Cmin [ Time Frame: Up to 48 months ]
Minimum serum concentration of drug
10. Pharmacokinetics - AUC [ Time Frame: Up to 48 months ]
Area under the curve
11. Pharmacokinetics - tmax [ Time Frame: Up to 48 months ]
Time to peak (maximum) serum concentration
12. Pharmacokinetics - t1/2 [ Time Frame: Up to 48 months ]
Terminal Half-life
13. Pharmacokinetics - accumulation index of CC-93269 [ Time Frame: Up to 48 months ]
Accumulation ratio of drug
14. 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
15. Evaluate measures of tumor sensitivity/ resistance to CC-93269 [ Time Frame: Up to 48 months ]
Measurement of tumor and immune factors

Eligibility Criteria
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.

2. Subject (male or female) is ≥ 18 years of age the time of signing the ICF.

3. Subject has a history of Multiple Myeloma (MM) with relapsed and refractory disease, and must have failed treatment with, are intolerant to or are not candidates for available therapies that are known to confer clinical benefit to patients with relapsed and refractory MM.

4. Subjects must have measurable disease (as determined by the central lab).

5. Subject consents to hospitalization for monitoring and collection of study peripheral blood samples.

6. Subject consents to serial bone marrow aspirations and/or biopsies during Screening, study treatment and at the end of treatment.

7. Subject has an Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.

8. Subjects must have adequate hematologic, liver, renal, and coagulation function as assessed by laboratory tests.

9. Females and males must practice true abstinence or agree to contraceptive methods throughout the study, and during the safety follow-up period.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Unless otherwise specified, Subject has received prior investigational therapy directed at B cell maturation antigen (BCMA). In selected cohort(s) of Parts A and B, prior therapy directed at BCMA may be required for enrollment

2. Subject has symptomatic central nervous system involvement of multiple myeloma.

3. Subject has non-secretory multiple myeloma, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis.

4. Subject is on chronic systemic immunosuppressive therapy or corticosteroids.

5. Subjects with clinically significant cardiac disease.

6. Subject had a prior autologous stem cell transplant ≤ 3 month prior to starting CC-93269.

7. Subject had a prior allogeneic stem cell transplant ≤ 12 month prior to starting CC-93269.

8. Subject had a prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting CC-93269, whichever is shorter. Subjects must have recovered from any clinically significant non-hematologic toxicities (ie, to Grade ≤1) of prior systemic anti-cancer directed treatments unless otherwise specified

9. Subject had major surgery ≤ 2 weeks prior to starting CC-93269.

10. Subject is a pregnant or lactating female.

11. Subject has known history or serologic evidence of human immunodeficiency virus (HIV) infection.

12. Subject has known history, virologic or serological evidence of hepatitis B or C virus (HBV/HCV) infection. Subjects who had HCV but have received an antiviral treatment and show no detectable HCV viral RNA for 6 months are eligible

13. Subject has a history of a venous thromboembolic event (VTE) within 6 months prior to study entry (eg, deep-vein thrombosis or pulmonary embolism). Subjects with distant history of VTE (ie, occurring > 6 months prior to study entry) who require ongoing treatment with chronic, therapeutic dosing of anti-coagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors) are eligible for study entry.

14. Subject has a history of concurrent second cancers requiring active, ongoing systemic treatment.

15. Subject has a history or presence of clinically relevant central nervous system (CNS) pathology.

16. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

17. Subject has any condition (eg, active or uncontrolled infection) including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. .

18. Subject has any condition that confounds the ability to interpret data from the study.

19. Inadequate pulmonary function.

20. Subject has active, uncontrolled, or suspected infection.


Contacts and Locations
Contacts

Contact:

Locations
United States, Alabama University of Alabama at Birmingham Birmingham
United States, California UCSF Medical Center San Francisco
United States, Connecticut Yale Cancer Center New Haven
United States, Georgia Winship Cancer Institute of Emory University Atlanta
United States, Michigan Henry Ford Medical Center - New Center One Detroit
United States, Washington Swedish Cancer Institute Seattle
Germany Universitatsklinikum Heidelberg Medizinische Klinik Krehl-Klinik Haematologie, Onkologie, Rheumato Heidelberg
Germany University of Tubingen Tübingen
Spain Clinica Universitaria de Navarra Pamplona
Spain Hospital Universitario de Salamanca Salamanca
Spain Hospital Universtario Marques de Valdecilla Santander
Spain Hospital Universitario Doctor Peset Valencia
Sweden Skanes Universitetssjukhus Lund Lund
Sponsors and Collaborators
Celgene
Investigator
Study Director : Michael R Burgess, MD, PhD Celgene
More Information
Responsible Party : Celgene
ClinicalTrials.gov Identifier : NCT03486067     
Other Study ID Numbers : CC-93269-MM-001, U1111-1210-6325, 2017-003448-19
First Posted : April 3, 2018
Last Update Posted : August 11, 2020
Last Verified : August 2020
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene: Multiple Myeloma
BCMA X CD3 T Cell
Antibody
CC-93269
Relapsed and Refractory
Additional relevant MeSH terms :
Multiple Myeloma
Neoplasms, Plasma Cell