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.
Inclusion Criteria:
1. Locally advanced, relapsed, and/or metastatic cancer
2. 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
3. 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.
4. 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:
1. Investigational therapy within 3 weeks prior to CMB305 dosing
2. Prior administration of other NY-ESO-1-targeting immunotherapeutics
3. Significant immunosuppression from:
1. Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic
corticosteroids at any dose, or
2. 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
4. Cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors,
G-CSF or GM-CSF within 3 weeks prior to the first scheduled CMB305 dosing
5. 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
6. 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
7. Myocardial infarction within 6 months of study initiation, active cardiac ischemia or
New York Heart Association (NYHA) Grade III or IV heart failure
8. Inadequate organ function including:
1. Marrow: Peripheral blood leukocyte count (WBC) < 3000/mm3, absolute neutrophil
count ≤ 1500/mm3, platelets < 75000/mm3, or hemoglobin < 10 gm/dL
2. 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)
3. Renal: Creatinine > 1.5x ULN
4. Other: INR (prothrombin time ratio) or partial thromboplastin time (PTT) >1.5 x
ULN
9. History of other cancer within 3 years (except non-melanoma cutaneous malignancies and
cervical carcinoma in situ).
10. Active tuberculosis or recent (< 2 week ago) clinically significant infection or
evidence of active hepatitis B, hepatitis C or HIV infection
11. For melanoma: Uveal melanoma or LDH >1.1 x ULN
12. Brain metastases considered unstable as:
1. Without confirmed stability over 60 days in patients previously treated with
prior surgery or radiation; OR
2. Associated with symptoms and/or findings; OR
3. Requiring corticosteroids or anticonvulsants in the prior 60 days
13. Pregnant, planning to become pregnant, or nursing
14. Known allergy(ies) to any component of CMB305 or CPA
