Safety and Tolerability of SYNB1891 Injection Alone or in Combination With Atezolizumab in Adult Participants

Stopped early · Phase 1

Conditions studied: Metastatic Solid Neoplasm, Lymphoma

In brief

This Phase 1, open-label, multicenter, 2-arm study was designed to evaluate SYNB1891 when administered either as monotherapy (Arm 1) or in combination with atezolizumab (Arm 2) in participants with advanced/metastatic solid tumors or lymphoma. The primary objective was to evaluate the safety and tolerability of study treatment, with a secondary objective of assessing preliminary tumor response to treatment and exploratory objectives of evaluating the pharmacokinetics/pharmacodynamics (PK/PD) of study treatment.

Key facts

Study ID

NCT04167137

Run by

Synlogic

People needed

32

Starts

2019-12-12

Expected to finish

2021-12-09

Last updated by the study team

2024-05-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Able and willing to voluntarily complete the informed consent process (participant or participant's representative).
• Adults aged ≥ 18 years (on the day of signing informed consent) with histologically- or cytologically-confirmed stage III or IV advanced/metastatic solid tumor or lymphoma for which no therapeutic options were available to extend survival or for which the participant was not a candidate for standard-of-care therapy.
• Eastern Cooperative Oncology Group performance status ≤ 1.
• Life expectancy ≥ 3 months.
• ≥ 1 injectable, measurable (≥ 10 mm in diameter, or ≥ 15 mm for nodal lesions), eligible lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Eisenhauer et al 2009), immune-related RECIST (iRECIST) (Seymour et al 2017), and/or Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Cheson et al 2016) and as assessed by the Investigator. Eligible lesions must not have been located in the thoracic cavity, spleen, pancreas, gastrointestinal tract (liver injection allowed), or cranium and must have been amenable to percutaneous injection and away from major blood vessels or neurological structures.
• Able to provide biopsies for biomarker analysis from injected and (if available) noninjected lesions at baseline and other time points during the study.
• Oxygen saturation > 90% without the use of supplemental oxygen.
• Adequate cardiac function, defined as follows:
• Left ventricular ejection fraction (LVEF) > 50% by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) performed within 6 months prior to the first dose of study treatment provided the participant had not received any potential cardiotoxic agents in the intervening period. Symptoms relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia must all have been Grade < 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
• QTc interval corrected for heart rate using Fridericia's formula (QTcF) < 480 msec at screening.
• Laboratory values within the following ranges:
• Absolute neutrophil count ≥ 1500/µL
• Lymphocyte count ≥ 500/µL
• Platelets ≥ 100,000/µL without transfusion
• Hemoglobin ≥ 9.0 g/dL (participants may have been transfused to meet this criterion)
• Estimated glomerular filtration rate (eGFR) > 50 mL/min/1.73 m\^2 per the Cockcroft-Gault formula
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN or ≤ 3 × ULN for participants with Gilbert's syndrome
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × ULN (AST and ALT ≤ 5 × ULN for participants with liver metastases and alkaline phosphatase ≤ 5 × ULN for participants with liver or bone metastases)
• International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant was receiving anticoagulant therapy as long as PT or aPTT was within therapeutic range of intended use of anticoagulants
• Agreed to use an acceptable method of contraception after informed consent, throughout the study, and for 5 months after the last dose of SYNB1891 or atezolizumab.
• Additional inclusion criteria that applied only to Arm 2 study participants were as follows:
• Thyroid-stimulating hormone (TSH) within the normal reference range or the participant was receiving stable thyroid replacement therapy.
• Participants must have received treatment with an anti-programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors (CPIs) or other therapies, if indicated (if CPI therapy was not indicated as a part of standard-of-care therapy, participants may have been CPI naïve).

You may not qualify if…

• Chemotherapy, radiation, or biological cancer therapy within 14 days prior to the first dose of study treatment, or failure of any adverse events (AEs) to recover to Baseline or NCI CTCAE version 5.0 Grade 1, except for any grade of alopecia caused by cancer therapeutics administered > 28 days earlier.
• Systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 28 days or 5 drug elimination half-lives (whichever was longer) prior to initiation of study treatment. CPIs were not considered systemic immunostimulatory agents for this criterion and were subject to the washout period listed in exclusion criterion #1.
• Allogeneic hematopoietic stem cell transplantation that required current use of immunosuppressors.
• Receipt of a live vaccine within 90 days prior to the first dose of study treatment or anticipation of a need for such a vaccine during treatment.
• Receipt of antibiotics within 7 days prior to the first dose of study treatment.
• Participation in a study of an investigational agent and receipt of study therapy or use of an investigational device within 28 days prior to the first dose of study treatment.
• Diagnosed immunodeficiency or current use of chronic systemic steroid therapy in excess of replacement doses (prednisone ≤ 10 mg/day or equivalent was acceptable) or any other form of immunosuppressive medication within 7 days prior to the first dose of study treatment.
• For injection and biopsy of visceral (deep) lesions: participants must not have been on long-acting antiplatelet agents such as aspirin or clopidogrel or on therapeutic doses of anticoagulants, with the exception of participants receiving a preventative dose of low molecular weight heparin. In participants receiving preventative low molecular weight heparin, treatment must have been stopped 24 hours before the intratumoral injection and resumed again 24 hours after the injection (Marabelle et al 2018).
• Previous or concurrent malignancy, with the exception of:
• Adequately treated basal or squamous cell carcinoma, in situ carcinoma of the cervix, or ductal carcinoma in situ of the breast;
• Localized prostate cancer definitively treated with surgery or radiation or stable on hormone therapy;
• Other cancer from which the participant had been disease free for at least 2 years.
• Clinically active central nervous system metastases and/or carcinomatous meningitis (treated brain metastases were permitted if radiologically stable for ≥ 28 days prior to the first dose of study treatment).
• Allergy to antibiotics that precluded treatment for infection with Escherichia coli Nissle 1917.
• Hepatitis B or C infection(s) unless screening tests indicated a negative viral load, and/or human immunodeficiency virus infection unless screening tests indicated a negative or below the limit of quantitation viral load.
• Known active tuberculosis.
• Grade 3 or higher infection according to NCI CTCAE within 28 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Failure to fully recover from the effects of major surgery. Surgeries that required general anesthesia must have been completed > 14 days before the first dose of study drug. Surgery requiring regional/epidural anesthesia must have been completed > 72 hours before the first dose of study treatment and participants should have recovered.
• Heart failure of New York Heart Association Class 3 or greater, restrictive cardiomyopathy, or unstable angina or recent myocardial infarction within 3 months prior to the first dose of study treatment.
• Any other medical condition that might have confounded the results of the study, interfered with the participant's participation, or was not in the best interest of the participant, in the opinion of the treating Investigator.
• Pregnant or breastfeeding or anticipated conception or fathering of children within the projected duration of the study and for 5 months after the last dose of SYNB1891 or atezolizumab.
• Additional exclusion criteria that applied only to Arm 2 study participants were as follows:
• History of immune-mediated AEs on prior PD-1/PD-L1 therapies requiring discontinuation or immunosuppressor therapy, excluding endocrinopathies.
• Active or history of underlying autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism who were on thyroid replacement hormone were eligible for the study.

Where it is running

• University of Colorado School of Medicine — Aurora, Colorado, United States
• Hackensack University John Theurer Cancer Center — Hackensack, New Jersey, United States
• Ohio State University College of Medicine — Columbus, Ohio, United States
• University of Pittsburgh Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
• Mary Crowley Cancer Research — Dallas, Texas, United States
• University of Texas MD Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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