| Eligibility |
Inclusion
Participants are eligible to be included in the study only if all of the following criteria
apply:
1. Be 18 years of age on day of signing informed consent
2. Subjects with histologically or cytologically confirmed advanced or metastatic solid
tumors who have disease progression after treatment with all available therapies for
metastatic disease that are known to confer clinical benefit, or are intolerant to
treatment, or refuse standard treatment. Note: there is no limit to the number of
prior treatment regimens
3. A male participant must agree to use contraception during the treatment period and for
at least 120 days after the last dose of study treatment and refrain from donating
sperm during this period
4. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP)
2. A WOCBP who agrees to follow contraceptive guidance during the treatment period
and for at least 120 days after the last dose of study treatment
3. A highly effective method of contraception is defined as one that results in a
low failure rate (i.e., less than 1% per year, when used consistently and
correctly)
5. Evidence of progressive disease (PD) within 3 months of signing the informed consent
form
6. Have measurable disease with at least 1 lesion meeting measurable criteria per
irRECIST as assessed by the local site investigator/radiology. Lesions situated in a
previously irradiated area are considered measurable if progression has been
demonstrated in such lesions
7. Eastern Cooperative Oncology Group (ECOG) score of 0 - 2
8. Minimum life expectancy of 3 months
9. Have adequate organ function. Specimens must be collected within 10 days prior to the
start of study treatment.
- Hematological: ANC =1500/µL; Platelets =100 000/µL; Hemoglobin =9.0 g/dL or =5.6
mmol/L
- Renal: serum creatinine = 1.5 times the ULN or estimated creatinine clearance =
60 mL/min (Cockcroft and Gault formula
[http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/])
- Hepatic: Total bilirubin =1.5 ×ULN or direct bilirubin =ULN for participants with
total bilirubin levels >1.5 × ULN; AST (SGOT) and ALT (SGPT) =2.5 × ULN (=5 × ULN
for participants with liver metastases)
- Prothrombin time (PT) and partial thromboplastin time (PTT) = 1.5 x ULN
10. Recovery (to baseline or to Grade 1 or less) from prior treatment-related toxicities
except alopecia. Participants with =Grade 2 neuropathy may be eligible. Note: If
participant received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting study treatment.
11. Ability to comply with treatment, laboratory monitoring and required clinic visits
12. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial
Exclusion
Participants are excluded from the study if any of the following criteria apply:
1. A Woman of Child Bearing Potential who has a positive urine pregnancy test (e.g.
within 72 hours) prior to treatment. If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required
2. Prior exposure to TLR 7 agonists, such as GS-9620, imiquimod, TMX 101, resiquimod,
MEDI9197, and 825A, or TLR 9 agonists such as SD-101, tilsotolimod (IMO-2125),
MGN1703, GNKG168, DUK-CPG-001 and CMP-001 for treatment of the solid tumor the subject
is currently being evaluated for treatment with BDB001.
3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor such as
CTLA-4, OX40, and CD137, and was discontinued from that treatment due to a Grade 3 or
higher irAE.
4. Received previous therapy for malignancy within 21 days prior to administration of
study drug, including any investigational agents (other than BDB001), chemotherapy,
immunotherapy, biological or hormonal therapy. Subjects receiving systemic interferons
or IL-2 must have discontinued the drug 4 weeks or 5 half-lives (whichever is longer)
prior to initiation of study treatment because these drugs could potentially increase
the risk of autoimmune conditions when given in combination with atezolizumab.
Subjects receiving nitrosoureas or mitomycin C must have discontinued the drug 6 weeks
prior to initiation of study treatment.
5. Subjects who are receiving a RANKL inhibitor such as denosumab prior to enrollment
must be willing and eligible to receive a bisphosphonate instead; denosumab could
potentially alter the activity and the safety of atezolizumab.
6. Major surgery within 4 weeks of first dose of study drug
7. Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease
8. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
9. Currently receiving medications known to be strong inhibitors of CYP1A and CYP3A and
strong/moderate inducers of CYP1A and CYP3A
10. Receiving systemic steroid therapy or any other form of immunosuppressive therapy
within 7 days prior to the first dose of study drug. The use of physiologic doses of
corticosteroids may be approved after consultation with the Sponsor.
11. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 21 days prior to the first dose of
study treatment. Note: Participants who have entered the follow-up phase of an
investigational study may participate as long as it has been 21 days after the last
dose of the previous investigational agent
12. History within last 6 months of New York Heart Association Class III or IV heart
failure, acute myocardial infarction, angina pectoris, uncontrolled arrhythmia, acute
coronary syndromes, stent placement, uncontrolled hypertension
13. QTc interval value > 470 msec (using Fridericia's Correction)
14. Left ventricular ejection fraction (LVEF) < 50% by echocardiogram (ECHO) or multigated
acquisition (MUGA) scan
15. Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment (Kim 2017). Brain MRI is preferred to document stability
of existing brain metastases. If MRI is medically contraindicated, CT with contrast is
an acceptable alternative.
16. Has severe hypersensitivity (=Grade 3) to atezolizumab and/or any of its excipients
17. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is
required unless mandated by local health authority
18. Known active hepatitis A, B or C. Subjects who are HBsAg+ and have DNA load < 2000
IU/mL (104 copies/mL) are eligible to participate in the study provided they meet the
ALT and bilirubin inclusion criteria.
19. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years with the exception of basal cell carcinoma of the skin,
squamous cell carcinoma of the skin that has undergone potentially curative therapy,
in situ cervical cancer, prostate cancer that is not actively being treated, and
malignancies which have been treated with curative surgery and have not recurred.
20. Has an active infection requiring systemic therapy
21. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator
22. Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study
23. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study treatment.
24. Has had an allogenic tissue/solid organ transplant
25. Active autoimmune disease that has required systemic treatment in past 2 years (i.e.,
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment and is allowed.
26. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis
27. History of interstitial lung disease
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