Clinical Trials /

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

NCT03831295

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SD-101 and BMS-986178 in Treating Patients With Advanced or Metastatic Solid Malignancies
  • 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]

Clinical Trial IDs

  • ORG STUDY ID: IRB-48546
  • SECONDARY ID: NCI-2019-00251
  • SECONDARY ID: VAR0175
  • SECONDARY ID: IRB-48546
  • NCT ID: NCT03831295

Conditions

  • Advanced Malignant Solid Neoplasm
  • Extracranial Solid Neoplasm
  • Metastatic Malignant Solid Neoplasm

Interventions

DrugSynonymsArms
Anti-OX40 Antibody BMS 986178BMS 986178, BMS-986178Treatment (SD-101, BMS-986178)
TLR9 Agonist SD-101ISS-ODN SD-101, SD-101Treatment (SD-101, BMS-986178)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability of intratumoral TLR9 agonist SD-101 (SD-101) in
      combination with intratumoral and intravenous anti-OX40 antibody BMS 986178 (BMS-986178) in
      patients with advanced solid tumors.

      SECONDARY OBJECTIVES:

      I. To evaluate the efficacy of treatment with intratumoral SD 101 in combination with
      intratumoral and intravenous BMS 986178 in patients with advanced solid tumors.

      II. To evaluate changes in pharmacodynamic endpoints in serial tumor biopsies from intratumor
      treated and untreated sites of disease.

      OUTLINE:

      SAFETY COHORT: Patients receive TLR9 agonist SD-101 intratumorally (IT) on days 1, 8 and 15.
      Patients also receive anti-OX40 antibody BMS 986178 IT on days 8 and 15, and intravenously
      (IV) over 30 minutes on days 8, 29 and 58.

      EXPANSION COHORT: Patients receive TLR9 agonist SD-101 IT on days 1, 8 and 15. Patients also
      receive anti-OX40 antibody BMS 986178 IT on days 1, 8 and 15, and IV over 30 minutes on days
      1, 29 and 58.

      After completion of study treatment, patients are followed up every 3-6 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (SD-101, BMS-986178)ExperimentalSAFETY COHORT: Patients receive TLR9 agonist SD-101 IT on days 1, 8 and 15. Patients also receive anti-OX40 antibody BMS 986178 IT on days 8 and 15, and IV over 30 minutes on days 8, 29 and 58. EXPANSION COHORT: Patients receive TLR9 agonist SD-101 IT on days 1, 8 and 15. Patients also receive anti-OX40 antibody BMS 986178 IT on days 1, 8 and 15, and IV over 30 minutes on days 1, 29 and 58.
  • Anti-OX40 Antibody BMS 986178
  • TLR9 Agonist SD-101

Eligibility Criteria

        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 disease that are >= 10 mm in diameter, one of
             which must be accessible for intratumoral injection and core biopsies and the other of
             which must be accessible for core 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 core 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
             negative

          -  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

          -  Patients with a history of other prior malignancy with the exception of non-melanoma
             skin cancer, carcinoma in situ of the cervix, in situ carcinoma of the bladder, or
             other malignancy that has undergone potentially curative therapy with no evidence of
             disease for the last > 2 years and is deemed by the investigator to be a low risk for
             recurrence

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events of intratumoral injections of study drugs
Time Frame:Up to week 96
Safety Issue:
Description:This outcome will be measured for any participant who has received at least one dose of any study medication. Treatment-limiting toxicities will be assessed using CTCAE v5.0. All adverse events will be recorded. Treatment-limiting toxicities are defined as; Hematologic toxicities: Febrile neutropenia; Grade 3 &4 thrombocytopenia; Grade 4 anemia unexplained with exception that toxicities can clearly be determined due to disease progression and/or unrelated to SD-101 or BMS-986178. Non-hematological toxicity ≥ Grade 3; Alopecia; Nausea; Grade 3 or 4 electrolyte abnormalities; Grade 3 or 4 elevation of amylase or lipase not associated with pancreatitis; Grade 3 endocrinopathy controlled by hormone replacement; Grade 3 infusion reaction that returns to Grade 1 in < 6 hours; Grade 3 skin rash not requiring systemic steroid therapy or other systemic immunosuppressive therapy. Doses should be delayed if any Grade ≥ 2 toxicities are not resolved to Grade ≤ 1 or baseline by next cycle.

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 3 years
Safety Issue:
Description:Tumor response assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions, and assessed by physical measurement; computed tomography (CT), positron emission tomography (PET)-CT. Complete Response (CR) = Disappearance of all target lesions Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions Overall Response (OR) = CR + PR Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) Stable disease (SD) = Small changes that do not meet any of the above criteria
Measure:Progression-Free survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:Progression-Free Survival is defined as the time elapsed between treatment initiation (Day 1) and tumor progression or death from any cause. Progression will be defined using RECIST v1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ronald Levy

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