Mogamulizumab in Treating Patients with Solid Tumors That Cannot Be Removed by Surgery
This phase I / II trial studies the safety and best dose of mogamulizumab and to see how well it works in treating patients with solid tumors that cannot be removed by surgery. Monoclonal antibodies, such as mogamulizumab, may block tumor growth in different ways by targeting certain cells that express C-C chemokine receptor 4 (CCR4).
- Informed consent form signed by the subject
- Histologically confirmed unresectable solid tumor malignancy with at least 1 measurable lesion in dose escalation; in the expansion phase, eligibility limited to metastatic triple negative breast cancer that has received prior taxane and anthracycline therapy; metastatic non-small cell lung cancer (NSCLC) that is not anaplastic lymphoma kinase positive (ALK+) and does not have a epidermal growth factor receptor (EGFR) sensitizing mutation; and metastatic gastric cancer
- Previously treated for advanced cancer and there are no curative therapy options available
- Karnofsky performance status >= 70 in the 30 day baseline period immediately prior to dosing
- All female subjects of child bearing age must be either surgically sterile, postmenopausal for at least 1 year, or using an acceptable method of contraception; examples of adequate methods of contraception include abstinence, intrauterine device, hormonal contraception, use of spermicide and a condom by sexual partner, or partner with a vasectomy; adequate contraception must be used from the beginning of the screening period until at least 16 weeks after the last dose of KW-0761; male subjects with partners of childbearing potential must use a barrier method of contraception from the day of the first dose of KW-0761 until at least 16 weeks after the last dose
- Creatinine (Cr) =< 1.5 X upper limit of normal (ULN)
- Total bilirubin (T-Bil) =< 1.5 X ULN (prior diagnosis or past history consistent with Gilbert's syndrome is an exception)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X ULN
- Platelets (Plts) >= 100,000 /uL
- Hemoglobin (Hgb) >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1000/mm^3
- Life expectancy > 12 weeks
- Previously treated for advanced cancer with no additional therapy options available known to prolong survival
- Evidence of clinically significant central nervous system (CNS) metastases or symptomatic CNS metastases within 30 days prior to dosing
- History of autoimmune disease, except for vitiligo, diabetes, and autoimmune thyroiditis
- A history of any major surgery within 6 weeks prior to dosing
- Any history of systemic anti-cancer therapy (standard or experimental) completed within 30 days prior to dosing, with the exception of palliative ablation of lesion(s) as long as measurable disease lesion(s) remain for evaluation of exploratory endpoints
- Any concomitant serious physical illness other than cancer (i.e., immune deficiency disease, bleeding disorder, etc.) within 1 year prior to dosing
- Any history of Stevens-Johnson syndrome
- Clinically significant heart disease, defined as New York Heart Association (NYH) class III or IV
- Any allergic reaction to a previously administered monoclonal antibody or other therapeutic protein
- Any significant systemic infection within 4 weeks prior to dosing
- Pregnancy or breast-feeding
- An existing diagnosis of human immunodeficiency virus (HIV), hepatitis B, hepatitis C, or any current laboratory findings or clinical signs and symptoms that suggest these conditions
- Subjects with active herpes simplex or herpes zoster; subjects with a history of herpes zoster who have had an outbreak within the last year will also be excluded; subjects on prophylaxis for herpes who started taking medication at least 30 days prior to study entry, should continue to take the prescribed medication for the duration of the study
- Unresolved immune-related adverse events following prior biological therapy
- Use of any investigational drugs within 30 days prior to dosing
- Any condition that requires or is likely to require treatment with systemic corticosteroids within the core study period and short term follow-up
- Subjects that have had a myocardial infarction within the last 6 months
- Subjects on any immunomodulatory drug
Locations & Contacts
Contact: Jedd David Wolchok
Trial Objectives and Outline
I. Determine safety and tolerability profiles, maximum tolerated dose (MTD) if achieved, recommended phase II dose (RP2D), and dose-limiting toxicity (DLT) of KW-0761 (mogamulizumab). (Phase I)
II. Determine the safety and preliminary efficacy of KW-0761 as determined by immune-related response criteria (irRC) in subjects with triple-negative breast cancer, non-small cell lung cancer, and gastric adenocarcinoma. (Phase II)
I. Explore the antitumor activity of KW-0761 using measures of activity; including best overall response rate (BORR), disease control rate, duration of response, time to response, and progression free survival (PFS) using both Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in cohorts of three specific tumor types treated at the MTD.
II. Evaluate the effect of KW-0761 on peripheral and intratumoral lymphocyte subset composition and function.
III. Evaluate the effect of KW-0761 on long-term safety.
I. Evaluate the effect of KW-0761 on the fecal microbiota.
II. Evaluate KW-0761 dose-response relationships.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive mogamulizumab intravenously (IV) over 1-2 hours on days 1, 8, 15, and 22 of course 1 and then on days 1 and 15 for all subsequent courses. Treatment repeats every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 2, 3, 6, 12, 18, and 24 weeks, and then at 6, 12, 18, and 24 months.
Trial Phase & Type
Memorial Sloan Kettering Cancer Center
Jedd David Wolchok
Secondary IDs NCI-2014-02287
Clinicaltrials.gov ID NCT02281409