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

NCT03831295 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: IRB-48546NCI-2019-00251VAR0175
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Advanced Malignant Solid Neoplasm; Extracranial Solid Neoplasm; Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (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.

  Up to week 96

Secondary Outcomes (2)

• Overall response rate

  Up to 3 years

• Progression-Free survival (PFS)

  Up to 3 years

Study Arms (1)

Treatment (SD-101, BMS-986178)

EXPERIMENTAL

SAFETY 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.

Biological: Anti-OX40 Antibody BMS 986178; Drug: TLR9 Agonist SD-101

Interventions

Anti-OX40 Antibody BMS 986178 BIOLOGICAL

Given IT or IV

Also known as: BMS 986178, BMS-986178

Treatment (SD-101, BMS-986178)

TLR9 Agonist SD-101 DRUG

Given IT

Also known as: ISS-ODN SD-101, SD-101

Treatment (SD-101, BMS-986178)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ronald Levy: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Related Publications (1)

• 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.

  PMID: 35135810 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Saad A Khan

  Stanford Cancer Institute Palo Alto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Robert K. and Helen K. Summy Professor in the School of Medicine

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: February 5, 2019
• Study Start: March 13, 2019
• Primary Completion: October 4, 2021
• Study Completion: October 4, 2021
• Last Updated: November 22, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)