- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02387125
Phase 1b Safety Study of CMB305 in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1
A Phase 1b Study Evaluating the Safety, Tolerability and Immunogenicity of CMB305 (Sequentially Administered LV305 and G305) in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is designed to investigate and examine the safety and immunogenicity of the combinatorial regimen called CMB305, where intradermal LV305 is administered sequentially with intramuscular G305 over three months. During Part 1, a dose escalation design will be utilized in patients with melanoma, NSCLC, ovarian cancer, or sarcoma. After completion of Part 1, the study will be expanded in Part 2 and will enroll patients with NSCLC, ovarian cancer, synovial sarcoma or myxoid/round cell liposarcoma. While this is an exploratory study to evaluate the safety, tolerability and immunogenicity of the CMB305 regimen, the study will also evaluate the safety and response to with oral metronomic CPA or intratumoral G100 in the context of CMB305.
CMB305 is a prime-boost vaccine approach against NY-ESO-1-expressing tumors, designed to generate an integrated, anti-NY-ESO-1 immune response in vivo via a targeted, specific interaction with dendritic cells.
G100 contains a potent synthetic small molecule toll-like receptor-4 (TLR-4) agonist, Glucopyranosyl Lipid A (GLA) that leverages the activation of both innate and adaptive immunity, including dendritic cells, in the tumor microenvironment to create an immune response against the tumor's preexisting diverse set of antigens.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Santa Monica, California, United States, 90403
- Sarcoma Oncology Center
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University
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Florida
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Ohio
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Cincinnati, Ohio, United States, 45267-0502
- University of Cincinnati Cancer Institute
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Texas
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
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Washington
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Seattle, Washington, United States, 98102
- Seattle Cancer Care Alliance
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Locally advanced, relapsed, and/or metastatic cancer
- Tumor histology consistent with one of the following: In Part 1, Dose Escalation - melanoma, NSCLC, ovarian cancer (including fallopian tube carcinoma), or sarcoma (any subtype). In Part 2, Patient Expansion - NSCLC, ovarian cancer (including fallopian tube carcinoma), or the sarcoma subtypes, synovial sarcoma or myxoid/round cell liposarcoma
- Tumor specimen positive for NY-ESO-1 expression by IHC and/or RT-PCR. At least one tumor must be accessible and patients must consent for biopsies in Arms C and D.
- Inadequate response, relapse, and/or unacceptable toxicity with one or more prior systemic, surgical, or radiation cancer therapies, and for whom curative standard therapy is not an option (except patients with NSCLC who must have experienced either an inadequate response, relapse, and/or unacceptable toxicity with two or more prior systemic, surgical, or radiation cancer therapies)
6. ≥ 18 years of age 7. Life expectancy of ≥ 6 months per the investigator 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 9. ECG without evidence of clinically significant arrhythmia or ischemia 10. If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use at least one highly effective or two effective contraceptive methods during the dosing period and for three months after last CMB305 injection 11. If male and sexually active with a FCBP, must agree to use highly effective contraception such as latex condom during the dosing period and for three months after last CMB305 injection
Exclusion Criteria:
- Investigational therapy within 3 weeks prior to CMB305 dosing
- Prior administration of other NY-ESO-1-targeting immunotherapeutics
Significant immunosuppression from:
- Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic corticosteroids at any dose, or
- Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine (antihistamines, non-steroidal anti-inflammatory drugs and aspirin permitted) or conditions such as common variable hypogamma-globulinemia or exposures such as large field radiotherapy
- Cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors, G-CSF or GM-CSF within 3 weeks prior to the first scheduled CMB305 dosing
- Psychiatric, other medical illness or other condition that in the opinion of the PI prevents compliance with study procedures or ability to provide valid informed consent
- Significant autoimmune disease with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy
- Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
Inadequate organ function including:
- Marrow: Peripheral blood leukocyte count (WBC) < 3000/mm3, absolute neutrophil count ≤ 1500/mm3, platelets < 75000/mm3, or hemoglobin < 10 gm/dL
- Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2.5 x ULN, total serum bilirubin > 1.5 x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ≤3.0 mg/dL)
- Renal: Creatinine > 1.5x ULN
- Other: INR (prothrombin time ratio) or partial thromboplastin time (PTT) >1.5 x ULN
- History of other cancer within 3 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ).
- Active tuberculosis or recent (< 2 week ago) clinically significant infection or evidence of active hepatitis B, hepatitis C or HIV infection
- For melanoma: Uveal melanoma or LDH >1.1 x ULN
Brain metastases considered unstable as:
- Without confirmed stability over 60 days in patients previously treated with prior surgery or radiation; OR
- Associated with symptoms and/or findings; OR
- Requiring corticosteroids or anticonvulsants in the prior 60 days
- Pregnant, planning to become pregnant, or nursing
- Known allergy(ies) to any component of CMB305 or CPA
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Part 1 Dose Escalation of CMB305
Patients with melanoma, NSCLC, ovarian cancer, or sarcoma will be enrolled.
Patients will receive CMB305, a sequential regimen of LV305 and G305.
Two cohorts are planned based on LV305 dose.
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EXPERIMENTAL: Part 2 Expansion of CMB305
Arm A will enroll up to 9 patients each with NSCLC or ovarian cancer, or up to 18 patients with the sarcoma subtypes, synovial sarcoma or MRCL.
Arm B will enroll up to 9 additional patients with selected sarcoma subtypes to explore subcutaneous (SC) dosing of LV305 and G305 on the same schedule.
Arm C will enroll up to 9 patients with synovial sarcoma or MRCL for treatment with CMB305 and with oral metronomic CPA.
Arm D will enroll up to 9 patients with synovial sarcoma or MRCL at selected sites for treatment with CMB305 and IT G100.
Arm E will enroll up to 6 patients with soft tissue sarcoma any subtype for treatment with a higher dose of CMB305 than previous arms.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The nature, frequency and severity of adverse events (AEs) and laboratory abnormalities in subjects receiving CMB305 alone or in combination with oral metronomic CPA or G100
Time Frame: Up to 5 years since first study injection
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To evaluate the safety and tolerability of CMB305 (sequential administered doses of LV305 and G305) alone or in combination with oral metronomic CPA or G100 in subjects with locally advanced, relapsed, or metastatic cancer expressing NY ESO 1
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Up to 5 years since first study injection
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Progression
Time Frame: Up to 5 years since first study injection
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To evaluate clinical responses (by Immune-related Response Criteria (irRC) modified to use RECIST (v 1.1) measurement criteria), time to progression (TTP) and progression-free survival (PFS) as a preliminary assessment of clinical activity
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Up to 5 years since first study injection
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Progression Free Survival
Time Frame: Up to 5 years since first study injection
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To evaluate clinical responses (by Immune-related Response Criteria (irRC) modified to use RECIST (v 1.1) measurement criteria), time to progression (TTP) and progression-free survival (PFS) as a preliminary assessment of clinical activity
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Up to 5 years since first study injection
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Overall Survival
Time Frame: Up to 5 years since first study injection
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Overall survival (OS), time to progression (TTP), and progression-free survival (PFS) and descriptive tumor responses.
Evaluation of response will be by RECIST (v1.1) modified to use irRC measurement criteria and by changes in markers of tumor burden
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Up to 5 years since first study injection
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Humoral and cellular immune responses at selected sites, as measured by changes from baseline anti-NY-ESO-1 immunity
Time Frame: Approximately 14 weeks
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To evaluate the cellular and humoral immunogenicity of CMB305 alone or in combination with mCPA or G100 in patients
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Approximately 14 weeks
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Other Outcome Measures
Outcome Measure |
Time Frame |
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To evaluate pre- and post-regimen blood samples for potential biomarkers of immunogenicity and clinical tumor response
Time Frame: Approximately 14 weeks
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Approximately 14 weeks
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To evaluate available pre- and post-regimen tumor tissue for histologic, immunohistologic, and genomic markers following administration of CMB305 alone or in combination with mCPA or G100
Time Frame: Approximately 14 weeks
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Approximately 14 weeks
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- V943A-001
- IMDZ-C131 (OTHER: ImmuneDesign Protocol Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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