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Advanced Malignant Solid NeoplasmPhase 1NCT03831295

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

A Phase 1 study testing Anti-OX40 Antibody BMS 986178 and TLR9 Agonist SD-101 in people with Advanced Malignant Solid Neoplasm and Extracranial Solid Neoplasm, run by Ronald Levy at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-OX40 Antibody BMS 986178 and TLR9 Agonist SD-101
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
13 Mar 2019to 4 Oct 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

Other trials in United States

About this study

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]

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. To evaluate the efficacy of treatment with intratumoral SD 101 in combination with intratumoral and intravenous BMS 986178 in patients with advanced solid tumors.
  2. To evaluate changes in pharmacodynamic endpoints in serial tumor biopsies from I TUMOR 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.

Being tested
Anti-OX40 Antibody BMS 986178, TLR9 Agonist SD-101
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-OX40 Antibody BMS 986178Biological

    Also called BMS 986178, BMS-986178

    Given IT or IV

  • TLR9 Agonist SD-101Drug

    Also called ISS-ODN SD-101, SD-101

    Given IT

Study groups in NCT03831295
Study groupRoleWhat they receive
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.
Receives: Biological: Anti-OX40 Antibody BMS 986178; Drug: TLR9 Agonist SD-101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events of intratumoral injections of study drugs

    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.

    Measured: Up to week 96

Secondary outcomes (2)

  1. Overall response rate

    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

    Measured: Up to 3 years

  2. Progression-Free survival (PFS)

    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.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2019
  2. Study start13 Mar 2019
  3. Primary completion4 Oct 2021
  4. Study completion4 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03831295
Sponsor's protocol ID
IRB-48546
Other IDs
NCI-2019-00251, VAR0175, IRB-48546
Status last verified
Sep 2023
First submitted
4 Feb 2019
Last updated
22 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022 Apr 1;82(7):1396-1408. doi: 10.1158/0008-5472.CAN-21-1382.

    PubMed 35135810

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-OX40 Antibody BMS 986178 and TLR9 Agonist SD-101 in people with Advanced Malignant Solid Neoplasm and Extracranial Solid Neoplasm, run by Ronald Levy at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events of intratumoral injections of study drugs (time frame: Up to week 96). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03831295, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.

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