A Phase 1b Safety Study of CMB305 (Sequentially Administered LV305 and G305) in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1
Describes the nature of a clinical study. Types include:
- Observational study — observes people and measures outcomes without affecting results.
- Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
- Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.
- Rochester, Minnesota: 14-009826
NCT ID: NCT02387125
Sponsor Protocol Number: IMDZ-C131
About this study
This is a Phase 1b, open label, multi-center study of CMB305 (sequentially administered LV305 [a dendritic cell-targeting viral vector expressing the NY-ESO-1 gene] and G305 [NY-ESO-1 recombinant protein plus GLA-SE]) in patients with melanoma, sarcoma, ovarian cancer, or non-small cell lung cancer that express NY-ESO-1. CMB305 is a novel in vivo approach designed to stimulate the body's immune system to fight the spread and growth of cancer for patients whose tumors express the NY-ESO-1 protein. LV305 will be given in a prime-boost approach with G305 to induce a synergistic immunotherapeutic response.
Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.See eligibility criteria
- Locally advanced, relapsed, and/or metastatic cancer with low or minimal tumor burden, which may or may not be measureable (see Appendix A for descriptions)
- 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
- If ovarian cancer, cancer antigen 125 (CA-125) must be ≥ 40 U/mL (unless patient has measureable disease that cannot be followed by CA-125); if melanoma, LDH must be ≤ ULN
- 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)
- ≥ 18 years of age
- Life expectancy of ≥ 6 months per the investigator
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- ECG without evidence of clinically significant arrhythmia or ischemia
- 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
- 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
- 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
- Uveal melanoma
- 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 or nursing
- Known allergy(ies) to any component of CMB305, including egg lecithin
Participating Mayo Clinic locations
Study statuses change often. Please contact us for help.
|Mayo Clinic Location
Mayo Clinic principal investigator
Matthew Block, M.D., Ph.D.
Open for enrollment
Cancer Center Clinical Trials Referral Office