Clinical Trials /

A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Participants With Relapsed and Refractory Multiple Myeloma

NCT04036461

Description:

Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), First-in-Human (FIH) clinical study of CC-99712 in monotherapy or combination in participants with relapsed and refractory multiple myeloma (MM). The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-99712, administered intravenously (IV) in monotherapy (Arm 1) or combination (Arm 2), to determine the maximum tolerated dose (MTD) of CC-99712 guided by a Bayesian logistic regression model (BLRM). A modified accelerated titration design will also be used for Arm 1 and Arm 2. The MTD may be established separately for CC-99712 administered at Q3W and/ or Q4W schedules. The expansion part (Part B) will further evaluate the safety and efficacy of CC-99712 in monotherapy (Arm 1) or combination (Arm 2) administered at or below the MTD in selected expansion cohorts in order to determine the RP2D. One or more doses or dosing regimens may be selected for cohort expansion. All participants will be treated until confirmed disease progression per IMWG criteria, unacceptable toxicity, or participants//Investigator decision to withdraw.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Participants With Relapsed and Refractory Multiple Myeloma
  • Official Title: A Phase 1, Multicenter, Open-label, Dose Finding Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CC-99712-MM-001
  • SECONDARY ID: U1111-1231-9404
  • SECONDARY ID: 2020-004514-35
  • NCT ID: NCT04036461

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CC-99712Arm 1 (CC-99712 monotherapy)
BMS-986405GSI (Gamma secretase inhibitor)Arm 2 (CC-99712 and BMS-986405 combination)

Purpose

Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), First-in-Human (FIH) clinical study of CC-99712 in monotherapy or combination in participants with relapsed and refractory multiple myeloma (MM). The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-99712, administered intravenously (IV) in monotherapy (Arm 1) or combination (Arm 2), to determine the maximum tolerated dose (MTD) of CC-99712 guided by a Bayesian logistic regression model (BLRM). A modified accelerated titration design will also be used for Arm 1 and Arm 2. The MTD may be established separately for CC-99712 administered at Q3W and/ or Q4W schedules. The expansion part (Part B) will further evaluate the safety and efficacy of CC-99712 in monotherapy (Arm 1) or combination (Arm 2) administered at or below the MTD in selected expansion cohorts in order to determine the RP2D. One or more doses or dosing regimens may be selected for cohort expansion. All participants will be treated until confirmed disease progression per IMWG criteria, unacceptable toxicity, or participants//Investigator decision to withdraw.

Trial Arms

NameTypeDescriptionInterventions
Arm 1 (CC-99712 monotherapy)ExperimentalCC-99712 will be administered via intravenous (IV) infusion once per 21-days on a Once every three weeks (Q3W) schedule, and once per 28-days on a Once every four weeks (Q4W) schedule
  • CC-99712
Arm 2 (CC-99712 and BMS-986405 combination)ExperimentalCC-99712 will be administered as indicated above. BMS-986405 will be administered orally TIW every week during a 21-day cycle (eg, Day 1, Day 3, Day 5, Day 8, Day 10, Day 12, Day 15, Day 17, and Day 19), with 48 hours between each dose with a week
  • CC-99712
  • BMS-986405

Eligibility Criteria

        Inclusion Criteria:

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

          1. Participant (male or female) is ≥ 18 years of age at the time of signing the informed
             consent form (ICF).

          2. Participant has a history of multiple myeloma (MM) with relapsed and refractory
             disease, and must:

               -  Have disease that is nonresponsive while on their last antimyeloma therapy or
                  documented disease progression on or within 60 days from the last dose of their
                  last antimyeloma therapy; and,

               -  Must have received at least 3 prior MM treatment regimens and,

               -  Must have received a proteasome inhibitor, an immunomodulatory agent and an
                  anti-CD38 antibody (eg, daratumumab); and,

               -  Should have failed treatment with or are intolerant to all established therapies.

          3. Participants must have measurable disease, including at least one of the criteria
             below:

               -  M-protein quantities ≥ 0.5 g/dL by sPEP or

               -  ≥ 200 mg/24 hours urine collection by uPEP or

               -  Serum FLC levels > 100 mg/L (milligrams/liter involved light chain) and an
                  abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine
                  M-protein or

               -  For participants with immunoglobulin class A (IgA) myeloma whose disease can only
                  be reliably measured by quantitative immunoglobulin measurement, a serum IgA
                  level ≥ 0.50 g/dL.

          4. Participant has an ECOG PS of 0-1.

          5. Participants must have the following laboratory values (determined by local
             laboratory):

               -  Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L without growth factor support for
                  7 days (14 days if pegfilgrastim)

               -  Platelets (plt) ≥ 75 x 10^9/L without transfusion for 7 days or plt ≥ 50 x 109/L
                  when BM plasma cells ≥ 50%.

               -  Potassium within normal limits or correctable with supplements.

               -  Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤
                  2.5 x upper limit of normal (ULN).

               -  Serum bilirubin ≤ 1.5 x ULN (or ≤ 2.0 x ULN for participants with documented
                  Gilbert's syndrome).

               -  Estimated serum creatinine clearance of ≥ 60 mL/min

               -  International normalized ratio (INR) < 1.5 x ULN and activated partial
                  thromboplastin time (APTT) < 1.5 x ULN.

          6. Females of childbearing potential (FCBP) must:

               -  Either commit to true abstinence from heterosexual contact (which must be
                  reviewed on a monthly basis and source documented) or agree to use, and be able
                  to comply with, at least two effective contraceptive methods (oral, injectable,
                  or implantable hormonal contraceptive; tubal ligation; intra-uterine device;
                  barrier contraceptive with spermicide; or vasectomized partner), one of which
                  must be barrier, from signing the ICF, throughout the study, during dose
                  interruptions, and for up to 42 days following the last dose of CC-99712; and

               -  Have two negative pregnancy tests as verified by the Investigator prior to
                  starting CC-99712. Participant must agree to ongoing pregnancy testing during the
                  course of the study, and after end of study treatment. This applies even if the
                  participant practices true abstinence from heterosexual contact. The participant
                  may not receive IP until the Investigator has verified that the result of the
                  pregnancy test is negative.

                    -  a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at
                       Screening

                    -  a negative serum or urine pregnancy test (Investigator's discretion) within
                       72 hours prior to Cycle 1 Day -1 of study treatment, and within 72 hours
                       prior to Day -1 of every subsequent cycle (note that the Screening serum
                       pregnancy test can be used as the test prior to Day -1 study treatment if it
                       is performed within the prior 72 hours). A serum or urine pregnancy test
                       (investigators discretion) must also be performed at the end of study for
                       each FCBP.

               -  Avoid conceiving for 42 days after the last dose of CC-99712.

               -  Agree to ongoing pregnancy testing during the course of the study, and after the
                  end of study treatment. This applies even if the participant practices true
                  abstinence2 from heterosexual contact.

               -  Males must practice true abstinence (which must be reviewed on a monthly basis)
                  or agree to use a condom (a latex condom is recommended) during sexual contact
                  with a pregnant female or a FCBP and will avoid conceiving from signing the ICF,
                  while participating in the study, during dose interruptions, and for at least 42
                  days following CC-99712 discontinuation, even if he has undergone a successful
                  vasectomy.

          7. Participant is willing and able to adhere to the study visit schedule and other
             protocol requirements.

        Exclusion Criteria:

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

          1. In Part A only, participant has received prior therapy directed at BCMA including, but
             not limited to, antibody-drug conjugates (BCMA-ADC), bispecific T cell-engaging
             antibodies or molecules, or BCMA-directed T cell therapy (eg, BCMA chimeric antigen
             receptor [CAR] T cells).

          2. Participant has symptomatic central nervous system involvement of MM.

          3. Participant has nonsecretory MM, plasma cell leukemia, Waldenstrom's
             macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy,
             monoclonal protein, and skin changes), or amyloidosis.

          4. Participants with a history of class III or IV congestive heart failure (CHF) or
             severe non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or
             ventricular arrhythmia within the previous 6 months prior to signing ICF.

          5. Participant had a prior autologous stem cell transplant ≤ 3 months prior to starting
             CC-99712.

          6. Participant had a prior allogeneic stem cell transplant with either standard or
             reduced intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic
             immunosuppression for graft-versus host disease.

          7. Participant had a prior chimeric antigen receptor T (CAR T) cell product ≤ 4 weeks
             prior to starting CC-99712.

          8. Participant had a prior systemic cancer-directed treatments or investigational
             modalities within 5 pharmacokinetic half-lives or 2 weeks prior to starting CC-99712,
             whichever is longer. The only exception is emergency use of a short course of
             corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum 4 days) before
             treatment.

          9. Participant had major surgery ≤ 2 weeks prior to starting CC-99712. Participants must
             have recovered from any clinically significant effects of recent surgery.

         10. Participant is a pregnant or lactating female.

         11. Participant has known human immunodeficiency virus (HIV) infection.

         12. Participant has known history of chronic, active hepatitis B or C virus (HBV/HCV)
             infection.

         13. Participant requires ongoing treatment with chronic, therapeutic dosing of
             anti-coagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).

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

         15. Participant has known history of cirrhosis or has clinically significant liver or
             biliary disease. Participants with stable chronic liver or biliary disease (such as
             Gilbert's syndrome, asymptomatic gallstones, or hepatobiliary involvement of
             malignancy) may participate in the study, however, sponsor medical monitor must be
             contacted for a discussion before enrollment.

         16. Participant has a history of clinically significant corneal disease requiring therapy
             or ongoing active corneal disease.

         17. Participant has active peripheral neuropathy or neuropathic pain Grade 2 or higher, as
             defined by the National Cancer Institute Common Terminology Criteria for Adverse
             Events (NCI-CTCAE v5.0).

         18. Participant has any significant medical condition, laboratory abnormality, or
             psychiatric illness that would prevent the participant from participating in the
             study.

         19. Participant has any condition including the presence of laboratory abnormalities, such
             as active or uncontrolled infection, which places the participant at unacceptable risk
             if he/she were to participate in the study.

         20. Participant has any condition that confounds the ability to interpret data from the
             study.

         21. Participant has confirmed extramedullary plasmacytoma in pulmonary, cardiac, or
             hepatic systems.

         22. Participant has documented malabsorptive syndromes including enteropathies,
             gastroenteritis (acute or chronic) or diarrhea (acute or chronic) with active
             treatment.

         23. Participant has previous SARS-CoV-2 infection within 10 days for mild or asymptomatic
             infections or 20 days for severe/critical illness prior to C1D1.

             • Acute symptoms must have resolved and based on investigator assessment in
             consultation with the medical monitor, there are no sequelae that would place the
             participant at a higher risk of receiving study treatment.

         24. Participant has previous SARS-CoV-2 vaccine within 14 days of C1D1. For vaccines
             requiring more than one dose, the full series (eg, both doses of a two-dose series)
             should be completed at least 14 days prior to C1D1 when feasible and when a delay in
             C1D1 would not put the study participant at risk.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:From enrollment until at least 42 days after completion of study treatment
Safety Issue:
Description:Number of participants with adverse event

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the proportion of participants who achieve a partial response or better (eg, Partial response (PR), Very good partial response (VGPR), Complete response (CR) or sCR), according to IMWG response criteria.
Measure:Time to Response
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the time from the first CC-99712 dose date to the date of first documented response (PR or better).
Measure:Duration of Response
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.
Measure:Progression-free Survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the time from the first dose of CC-99712 to progressive disease (PD) or death from any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:Is defined as the time from the first dose of CC-99712 to death from any cause.
Measure:Pharmacokinetics- Cmax
Time Frame:Up to 3 years
Safety Issue:
Description:Maximum plasma concentration of drug
Measure:Pharmacokinetics- Cmin
Time Frame:Up to 3 years
Safety Issue:
Description:Minimum plasma concentration of drug
Measure:Pharmacokinetics- AUC
Time Frame:Up to 3 years
Safety Issue:
Description:Area under the curve
Measure:Pharmacokinetics- tmax
Time Frame:Up to 3 years
Safety Issue:
Description:Time to peak (maximum) serum concentration
Measure:Pharmacokinetics- t1/2
Time Frame:Up to 3 years
Safety Issue:
Description:Half-life
Measure:Pharmacokinetics- CL
Time Frame:Up to 3 years
Safety Issue:
Description:Clearance
Measure:Pharmacokinetics- Vss
Time Frame:Up to 3 years
Safety Issue:
Description:Volume of Distribution
Measure:Presence and frequency of ADA using a validated bridging immunoassay with electrochemiluminescence detection
Time Frame:Up to 3 years
Safety Issue:
Description:Anti-CC-99712 antibodies

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Multiple Myeloma
  • Relapsed and refractory
  • CC-99712
  • BCMA
  • Antibody drug conjugate
  • BMS-986405

Last Updated

August 18, 2021