Metastatic, GPNMB Over-Expressing, Triple-Negative Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: CDX-011, Glembatumumab vedotin
Product Code: CDX-011
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: Glem
Sponsors
Celldex Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients may be included in the study only if they meet all of the following inclusion criteria at the time of randomization: 1. Female or male subjects with metastatic, histologically or cytologically confirmed carcinoma of the breast. 2. Documented progression of disease, based on radiographic, clinical or pathologic assessment showing increased tumor burden or new site(s) of disease during or subsequent to the last anticancer regimen received. 3. Overexpression of GPNMB (= 25% of malignant epithelial cells expressing GPNMB, as determined by a central laboratory using IHC methods) in at least one tumor sample obtained in the advanced setting. 4. Triple-negative status determined in a tumor sample obtained in the advanced setting, according to the following criteria: a. Minimal or no expression of estrogen and progesterone receptors ( 40 mL/min per the Cockcroft and Gault formula (Appendix 5). 15. Adequate liver function as assessed by total bilirubin = 1.5 x upper limit of normal (ULN), and alanine transaminase (ALT) and aspartate transaminase (AST) = 3.0 x ULN (= 5.0 x ULN in the case of liver metastases). Patients with known Gilbert’s syndrome may be enrolled with total bilirubin = 3.0 mg/dL. 16. Read, understood, and provided written informed consent and, if applicable, HIPAA authorization.
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study for any of the following reasons: 1. Progression/recurrence of breast cancer during or within 3 months of completion of neoadjuvant or adjuvant chemotherapy. 2. Investigational therapy within four weeks before planned start of study treatment. 3. Persistent neuropathy > NCI-CTCAE v. 4.0 Grade 1 (at randomization). 4. History of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin. Compounds of similar composition include Auristatin PHE as an anti-fungal agent, Auristatin PE (TZT-1027, Soblidotin, NSC-654663) as an anti-tumor agent and symplostatin 1 as an anti-tumor agent. 5. Known hypersensitivity to 5-flourouracil, capecitabine or any of its components. 6. Known dihydropyrimidine dehydrogenase (DPD) deficiency. 7. Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months prior to randomization. Continued use of steroids and/or anticonvulsants (in the absence of any suspicion of progressive brain metastases) is acceptable. 8. Subjects unable to provide informed consent and/or unable to comply with the study procedures. 9. Pregnant or breast-feeding women, and women or men who are not willing to use effective contraception during the time from signing of informed consent through two months after the last dose of study treatment. Effective contraception is defined as double barrier contraception (e.g., condom plus spermicide in combination with a female condom, diaphragm, cervical cap, contraceptive sponge or vaginal ring), intra-uterine device (IUD), implants, injectables, combined oral contraceptives, sexual abstinence (total abstinence from sexual intercourse as the preferred lifestyle of the subject; periodic abstinence is not acceptable), or sexual intercourse with only a vasectomized partner. Patients and/or partners who are surgically sterile or postmenopausal are exempt from this requirement. 10. Previously received capecitabine and discontinued due to progressive disease or intolerance; previously received CDX-011 (CR011-vcMMAE; glematumumab vedotin) or other MMAE-containing agents. 11. Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary. Note: microscopic examination of urinalysis is required during screening. If urinary infection is suspected, then a negative urine culture is required prior to enrollment. 12. Chronic use of systemic corticosteroids above the physiologic dose (5 mg per day prednisone or equivalent) within 7 days of enrollment, except for premedication. 13. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, and congestive heart failure (New York Heart Association class 3 or 4), a history of a serious uncontrollable arrhythmia despite treatment, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry. 14. Any underlying medical condition that, in the investigator’s opinion, will make the administration of study treatment (CDX-011 or capecitabine) hazardous to the patient, or would obscure the interpretation of adverse events. 15. Other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the anti-cancer activity of CDX-011 in metastatic, GPNMB over-expressing, triple-negative breast cancer as measured by the duration of progression-free survival (PFS).; Secondary Objective: Secondary objectives are: • To further assess the anti-cancer activity of CDX-011 in metastatic, GPNMB over-expressing, triple-negative breast cancer, as assessed by the objective response rate (ORR), duration of response (DOR) and overall survival (OS). • To further characterize the safety of CDX-011 in metastatic, GPNMB over-expressing, triple-negative breast cancer. • To obtain pharmacokinetic parameters and to explore the relationships between patient-specific measures of exposure and safety and activity parameters ; Primary end point(s): Primary end point: • Duration of progression-free survival (PFS) ;Timepoint(s) of evaluation of this end point: Under the assumption of exponential distribution for each arm and uniform enrollment over 2 years, and 10% drop out rate (PFS events cannot be observed), 300 patients (200 in the CDX-011 arm and 100 in the capecitabine arm) are needed, and it is anticipated that 203 PFS events will be observed in approximately 26 months from the date the first patient is randomized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end points: • Objective response rate (ORR) • Duration of response (DOR) • Overall survival (OS) ; Timepoint(s) of evaluation of this end point: Objective response rate (ORR) is defined as the proportion of patients who achieve a best overall response of complete or partial response according to RECIST 1.1. The primary analysis of ORR will be based upon evaluations by the IRC. Duration of objective response is defined as the number of months from the time criteria are first met for either CR or PR, until the first date that PD is objectively documented. The duration of objective response will be summarized descriptively using the Kaplan-Meier method. Overall survival (OS) is defined as the number of months from randomization to the date of death due to any cause. | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactDirector of Regulatory Affairs
Celldex Therapeutics, Inc.
Outcome results
None listed