Study of ONT-10 and Varlilumab to Treat Advanced Ovarian or Breast Cancer

NCT02270372 | Completed Phase 1 DMC

• 1 other identifier: ONT-10-104
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

This is a two-part Phase 1b, open-label study of ONT 10 administered in combination with varlilumab. Two different doses of varlilumab will be studied in combination with the single agent recommended dose of ONT 10. Intermediate and/or lower doses of varlilumab or ONT-10 may also be studied at the recommendation of the safety monitoring committee (SMC).

Conditions

Advanced Breast Carcinoma; Advanced Ovarian Carcinoma

Keywords

Advanced breast carcinoma; Advanced ovarian carcinoma; MUC1; vaccine; Phase 1b

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events as a measure of safety and tolerability

  Assessment of the adverse event profile as an indication of overall safety and tolerability of the combination treatment with ONT-10 and varlilumab

  Cycles of 12 weeks

Secondary Outcomes (1)

• Immune Response to MUC1

  8 weeks on a weekly basis, followed by every 6 weeks

Study Arms (1)

Drug Combination

EXPERIMENTAL

The drug combination of ONT-10 and varilumab

Biological: ONT-10, Varlilumab combination

Interventions

ONT-10, Varlilumab combination BIOLOGICAL

ONT-10 a liposomal synthetic glycopolypeptide MUC1 targeted antigen formulated with PET Lipid A adjuvant. Varlilumab is a recombinant, fully human mAb of the IgG1κ isotype that specifically binds human CD27.

Drug Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be at least 18 years of age at the time of consent
• Life expectancy of at least 6 months, in the opinion of the investigator
• Have histologically confirmed breast or ovarian carcinoma
• Have evidence of persistent, recurrent, or progressive disease for which there is no known or established treatment available with curative intent, after at least one course of systemic therapy for locally advanced or metastatic disease , including chemotherapy, targeted therapy (small molecule or antibody based), or hormonal therapy
• Measurable or evaluable disease by RECIST 1.1
• ECOG performed status of 0 or 1
• Adequate hematologic function defined by:
• WBC count ≥ 3.0 x 103 cells/µL
• Lymphocyte count ≥ 0.8 x 103 cells/µL
• Platelet count ≥ 75 x 103 /µL, and
• Hemoglobin ≥ 9 g/dL
• Have renal and hepatic function as defined by:
• AST and ALT ≤ 2.5 X ULN
• Total bilirubin ≤ 1.5 X ULN. Patients with elevated bilirubin known to be due to Gilbert's disease may be enrolled after approval from the medical monitor, and
• Creatinine clearance ≥ 50 mL/min

You may not qualify if:

• Has medical, social, or psychological factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures
• Is pregnant, breastfeeding, or planning a pregnancy
• Has received treatment with any systemic anticancer therapy, wide-field radiation, or experimental agent within 4 weeks of receiving cyclophosphamide on Day -3, with the exception of anticancer hormonal therapy, which may not be given within 2 weeks of receiving cyclophosphamide on Day -3. All residual toxicity related to prior anticancer therapies (excluding vitiligo, endocrinopathies on stable replacement therapy, alopecia and Grade 2 fatigue) must resolve to Grade 1 severity or less or return to baseline prior to receipt of study treatment.
• Has received treatment with focal radiotherapy within 2 weeks, or radiopharmaceuticals (e.g., strontium, samarium) within 8 weeks of receiving cyclophosphamide on Day -3
• Has untreated or uncontrolled CNS metastases, including patients who require glucocorticoid therapy for CNS metastases
• Has received prior treatment with ONT-10 or varlilumab, or prior treatment with other MUC1 vaccines or CD27-targeted agents
• Has active autoimmune disease or a documented history of autoimmune disease, or history of potential autoimmune syndrome that required systemic steroids or immunosuppressive medications, except for patients with vitiligo, endocrinopathies, type 1 diabetes, or patients with resolved childhood asthma/atopy or other syndromes which would not be expected to recur in the absence of an external trigger (e.g., drug-related serum sickness or post-streptococcal glomerulonephritis). Patients with mild asthma who require intermittent use of bronchodilators (such as albuterol) who have not been hospitalized for asthma in the preceding 3 years will not be excluded from this study.
• Has recognized immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia, and/or other hereditary congenital immunodeficiencies
• Has any pre-existing medical condition requiring systemic chronic steroid or immunosuppressive therapy
• a) Inhaled corticosteroids for COPD or topical steroids are allowed
• Known to be positive for HIV, or to have active hepatitis B, or hepatitis C, or have active infection of any kind requiring systemic therapy
• Administration of any other vaccine ≤ 4 weeks of receiving cyclophosphamide on Day -3
• Underlying medical condition that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination of adverse events. This includes other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancer; or any other cancer from which the patient has been disease-free for at least 3 years.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension (persistent systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications) or arrhythmia, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or myocardial infarction within 6 months prior to the first dose of study treatment

Sponsors & Collaborators

• Cascadian Therapeutics Inc.: lead
• Celldex Therapeutics: collaborator

Study Sites (4)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

NYU Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: October 21, 2014
• Study Start: November 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: May 17, 2018

Record last verified: 2016-08

Locations

US (4)