SD-101 and BMS-986178 in Treating Patients With Advanced or Metastatic Solid Malignancies

Not Recruiting

Trial ID: NCT03831295


This phase I trial studies the side effects of intratumoral injection of SD-101 and BMS-986178 in treating patients with solid malignancies that have spread to other places in the body. The TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. BMS-986178 is a monoclonal anti-OX40 antibody that enhances the activation of T cells, immune cells that are important for fighting tumors. Giving TLR9 agonist SD-101 together with anti-OX40 antibody BMS-986178 may work better in treating patients with advanced solid tumors.

Official Title

Intratumoral Injection of SD-101, an Immunostimulatory CpG Oligonucleotide, in Combination With BMS- 986178, an OX40 Agonist Antibody, in Advanced Solid Malignancies [CA012-014]

Stanford Investigator(s)

Saad A. Khan, MD
Saad A. Khan, MD

Associate Professor of Medicine (Oncology)


Inclusion Criteria:

   - Any advanced/metastatic, non-hematological, extracranial solid tumor malignancy with
   disease progression after at least one line of standard therapy or for which standard
   therapy known to prolong survival does not exist

   - Patients must have at least two sites of non-osseous disease that are ≥10mm in
   diameter, one of which must be accessible for intratumoral injection and tumor
   biopsies and the other of which must be accessible for needle biopsies by
   interventional radiology. (Sites have to be deemed safe for repeated access upon IR
   review, based on anatomic location, size, shape, and accessibility). Liver lesions may
   not be used as the injection site even if otherwise deemed safe for access.

   - Patients must have at least one additional site of measurable disease by Response
   Evaluation Criteria in Solid Tumors (RECIST) criteria, other than the sites selected
   for intratumoral injection and tumor biopsies

   - All patients with tumor types for which anti-PD-1 or anti PD-L1 therapy has been
   approved should have received such therapy prior to enrollment, with evidence of
   progression on at least two scans (ie, with pseudoprogression ruled out). Patients
   with validated driver mutations should have received and progressed on appropriate
   targeted therapy

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

   - Life expectancy of at least three months

   - Total bilirubin < 1.5 x upper limit of normal (ULN) (unless patient has history of
   Gilbert?s disease)

   - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x upper limit
   of normal (ULN)

   - Creatinine < 1.5 x ULN or measured or calculated creatinine clearance (glomerular
   filtration rate [GFR] can also be used in place of creatinine or creatinine [CrCl]) >=
   60 mL/min for subject with creatinine levels > 1.5 x ULN

   - Absolute neutrophil count (ANC) >= 1,500/mcL

   - Hemoglobin >= 9 g/dL without transfusion within the past 4 weeks

   - Platelets >= 100,000/mcL

   - Prothrombin time (PT)/international normalized ratio (lNR) within normal limits

   - Written informed consent obtained from subject

   - Patients who have previously received an immune checkpoint inhibitor prior to
   enrollment must have any immune related toxicities resolved to =< grade 1 or baseline
   (prior to the checkpoint inhibitor) to be eligible. Patients who developed endocrine
   adverse events on checkpoint inhibitor are eligible to enter regardless of the Common
   Terminology Criteria for Adverse Events (CTCAE) Grade resolution as long as the
   patient is well controlled on endocrine replacement

   - Women of childbearing potential must have a urine or serum pregnancy test within 24
   hours prior to the first dose of trial treatment. If the urine test is positive or
   cannot be confirmed as negative, then a serum test will need to be negative

   - Women of childbearing potential must practice a highly effective method of birth
   control during treatment and for 160 days after treatment completion. Women of
   childbearing potential who chose complete abstinence must agree to have a urine or
   serum pregnancy tests within 24h of each dose of study treatment. If the urine test is
   positive or cannot be confirmed as negative, then a serum test will need to be

   - Men who are sexually active with women of childbearing potential must agree to follow
   instructions for methods of contraception while being treated on the study, and for
   165 days after treatment completion. Men must agree to not donate sperm during this
   time period

Exclusion Criteria:

   - History of grade 2 or higher hypersensitivity reaction to either SD-101 or BMS-986178

   - Patients who require immediate treatment or cytoreduction, as deemed by their
   physician or the study investigators

   - Treatment with other anticancer therapy (chemotherapy, small molecule, or radiation
   therapy) within the past 3 weeks prior to study entry or within the past 6 weeks prior
   to study entry for immunotherapies

   - Use of investigational agent within the past 3 weeks prior to study enrollment

   - Major surgery within 4 weeks of enrollment, or a wound that has not fully healed

   - Vaccinated with live, attenuated vaccines within 4 weeks of enrollment

   - Symptomatic central nervous system (CNS) metastases

   - Known bleeding disorder that is deemed to place the patient at unacceptable risk for
   bleeding complications from intratumoral injection. Patients on anticoagulants and
   anti-platelet agents other than aspirin are excluded

   - Any uncontrolled bacterial, fungal, viral, or other infection

   - Active autoimmune disease requiring systemic treatment within the past 2 years, with
   the exception of patients well controlled on physiologic endocrine replacement

   - Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other
   immune suppressive drugs within 14 days prior to initiation of study drug. Steroids
   for topical ophthalmic, inhaled, or nasal administration are allowed. Patients
   requiring courses of systemic steroids for 14 consecutive days or less for an acute
   condition (not for a chronic autoimmune illness) may receive study drug 14 days after
   steroid therapy

   - Prior history of cancer that is unlikely to interfere with the ability to give study
   treatment or affect the primary outcome or interpretation of the primary outcome of
   the study. For a history of malignancy treated with curative intent, enrollment should
   occur at least 2 years after such therapy.

   - Significant cardiac disease (New York Heart Association [NYHA] class IV congestive
   heart failure, or unstable angina or myocardial infarction within the past 6 months)

   - Human immunodeficiency virus (HIV) positive (+) patients or patients with active
   hepatitis B or C infection

   - Patients who are pregnant or breastfeeding

   - Any other medical history, including laboratory results, deemed by the investigator
   likely to interfere with their participation in the study, or to interfere with the
   interpretation of the results


biological: Anti-OX40 Antibody BMS 986178

drug: TLR9 Agonist SD-101

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Melanie Ashland

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