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

Study 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 subjects 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), to determine the maximum tolerated dose (MTD) and non-tolerated dose (NTD) of CC-99712 using a modified accelerated titration design and Bayesian methodology. The MTD and NTD 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 administered at or below the MTD in selected expansion cohorts in order to determine the RP2D. One or more dosing regimens may be selected for cohort expansion. All subjects will be treated until confirmed disease progression per IMWG criteria, unacceptable toxicity, or subject/Investigator decision to withdraw.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study: 1. Subject (male or female) is ≥ 18 years of age at the time of signing the ICF. 2. Subject has a history of 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. Subjects 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 subjects 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. Subject has an ECOG PS of 0-1. 5. Subjects must have the following laboratory values (determined by local laboratory):
  • - Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L.
  • - Platelets (plt) ≥ 75 x 10^9/L.
  • - 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 subjects with documented Gilbert's syndrome).
  • - Estimated serum creatinine clearance of ≥ 60 mL/min.
  • - International normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 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.
Subject must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact. The subject 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-99712.7.
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. 8. Subject 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 subject from enrollment: 1. In Part A only, subject has received prior investigational therapy directed at BCMA. 2. Subject has symptomatic central nervous system involvement of MM. 3. Subject has nonsecretory MM, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis. 4. Subjects 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. Subject had a prior autologous stem cell transplant ≤ 3 months prior to starting CC-99712. 6. Subject 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. Subject had a prior chimeric antigen receptor T (CAR T) cell product ≤ 4 weeks prior to starting CC-99712. 8. Subject 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. Subject had major surgery ≤ 2 weeks prior to starting CC-99712. Subjects must have recovered from any clinically significant effects of recent surgery. 10. Subject is a pregnant or lactating female. 11. Subject has known human immunodeficiency virus (HIV) infection. 12. Subject has known history of chronic, active hepatitis B or C virus (HBV/HCV) infection. 13. Subject requires ongoing treatment with chronic, therapeutic dosing of anti-coagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors). 14. Subject has a history of concurrent second cancers requiring active, ongoing systemic treatment. 15. Subject has known history of cirrhosis or has clinically significant liver or biliary disease. Subjects 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. Subject has a history of clinically significant corneal disease requiring therapy or ongoing active corneal disease. 17. Subject 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).

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04036461
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Celgene
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Kaida Wu, MD, PhD
Principal Investigator Affiliation Translational Development.
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Canada, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Arms & Interventions

Arms

Experimental: Administration of CC-99712

CC-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

Interventions

Drug: - CC-99712

CC-99712

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

La Jolla, California

Status

Recruiting

Address

University of California San Diego Moores Cancer Center

La Jolla, California, 92093

Florida Cancer Specialists, Sarasota, Florida

Status

Recruiting

Address

Florida Cancer Specialists

Sarasota, Florida, 34232

Roswell Park Cancer Institute, Buffalo, New York

Status

Recruiting

Address

Roswell Park Cancer Institute

Buffalo, New York, 14263

Mount Sinai Hospital, New York, New York

Status

Recruiting

Address

Mount Sinai Hospital

New York, New York, 10029

Oregon Health & Science University, Portland, Oregon

Status

Recruiting

Address

Oregon Health & Science University

Portland, Oregon, 97239

UT Southwestern Medical Center, Dallas, Texas

Status

Recruiting

Address

UT Southwestern Medical Center

Dallas, Texas, 75390

Swedish Medical Center, Seattle, Washington

Status

Recruiting

Address

Swedish Medical Center

Seattle, Washington, 98104

International Sites

Tom Baker Cancer Center, Calgary, Alberta, Canada

Status

Not yet recruiting

Address

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2

Princess Margaret Cancer Centre, Toronto, Ontario, Canada

Status

Recruiting

Address

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9

Montreal, Quebec, Canada

Status

Not yet recruiting

Address

Hopital Maisonneuve Rosemont dba CIUSSS de lEst de lIle de Montreal

Montreal, Quebec, H1T 2M4