Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

SYNB1891 monotherapy was administered as an IT injection on Days 1, 8, and 15 of Cycle 1 and Day 1 of subsequent cycles for up to 24 months/35 cycles. The starting dose of SYNB1891 in the first cohort was 1 × 10\^6 live cells and was increased in approximately 3-fold increments in subsequent cohorts.

SYNB1891 was administered as an IT injection on Days 1, 8, and 15 of Cycle 1 and Day 1 of subsequent cycles for up to 24 months/35 cycles. The dose of SYNB1891 in the first cohort was 1 × 10\^7 live cells and was increased in an approximately 3-fold increment to 3 × 10\^7 live cells in the second cohort.

Atezolizumab was administered in accordance with its recommended dose and schedule (1200 mg IV Q3W) on Day 1 of each cycle for up to 24 months/35 cycles. On days when atezolizumab and SYNB1891 were both administered, SYNB1891 was administered first, followed by at least 1 hour of observation prior to the atezolizumab infusion.

SYNB1891 was administered as an IT injection over a dose range of 1 x 10\^6 to 3 x 10\^8 live cells in Arm 1 and 1 x 10\^7 to 3 x 10\^7 in Arm 2.

SYNB1891

Atezolizumab was administered in accordance with its recommended dose and schedule (1200 mg IV Q3W).

Aoife Brennan, MB, BCh, BAO, MMSc

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.

Arm 1 comprised intratumoral (IT) injections of SYNB1891 monotherapy to determine the single-agent maximum tolerated dose (MTD). The starting dose of SYNB1891 in the first cohort was 1 × 10\^6 live cells and was increased in approximately 3-fold increments in subsequent cohorts until MTD determination in accordance with the modified toxicity probability interval (mTPI) algorithm (Ji et al 2013). Dose escalation was to proceed until the target dose-limiting toxicity (DLT) range (approximately 30%) for SYNB1891 monotherapy was determined based on DLTs observed in Cycle 1. The dose selected as achieving the target DLT range was to be considered the MTD. DLTs were defined in the protocol as certain treatment-related Grade 3/4 laboratory values, sepsis, toxicity resulting in death, discontinuation of Cycle 1, or delay of Cycle 2.

Arm 2 comprised IT injections of SYNB1891 combined with standard dose atezolizumab (1200 mg intravenously \[IV\] every 3 weeks \[Q3W\]). Arm 2 dosing began after all participants in Arm 1 Cohort 4 completed their Cycle 1 DLT safety evaluation. The starting dose of IT SYNB1891 in the first cohort of Arm 2 was at the SYNB1891 Arm 1 Cohort 3 dose level. SYNB1891 dosing in the Arm 2 cohorts increased in approximately 3-fold increments in subsequent cohorts until recommended Phase 2 dose (RP2D) determination. SYNB1891 combination dosing in Arm 2 was always at least 1 dose level below the SYNB1891 monotherapy dose being evaluated in Arm 1, with combination doses not escalated above the SYNB1891 single-agent MTD established in Arm 1.

In both arms, after an initial 4 cycles (21 days per cycle) of study treatment, participants who did not have progressive disease may have received additional cycles of their assigned study treatment for up to 24 months (i.e., Cycles 5 to 35) after the initial dose.

The maximum time of study participation for a participant may have been up to 26 months, including the screening period (up to 28 days), treatment administration period (up to 24 months), and Safety Follow-up period (30 ± 5 days after the last dose).

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

A Phase 1, Open-label, Multicenter Study of SYNB1891 Administered by Intratumoral Injection to Patients With Advanced/Metastatic Solid Tumors and Lymphoma Alone and in Combination With Atezolizumab

The following adverse events (AEs) were DLTs if they occurred in Cycle 1 and were assessed by the Investigator as related to treatment:

1. Grade (Gr) 4 nonhematologic toxicity (not laboratory)
2. Gr 4 hematologic toxicity ≥ 7 days, any Gr 4 thrombocytopenia, or Gr 3 thrombocytopenia with significant bleeding
3. Gr ≥ 3 nonhematologic toxicity (exceptions: Gr 3 fatigue ≤ 3 days; Gr 3 diarrhea, nausea, or vomiting without treatment; Gr 3 rash without treatment)
4. Gr 3/4 nonhematologic laboratory value for \> 1 week or resulting in significant medical intervention, hospitalization, or drug-induced liver injury (exceptions: clinically nonsignificant, treatable, or reversible laboratory abnormalities)
5. Gr 3/4 febrile neutropenia
6. Sepsis, severe abscesses and/or ulcerations requiring surgical management
7. Toxicity delaying Cycle 2 initiation \>2 weeks
8. Toxicity causing treatment discontinuation
9. Gr 3 toxicity causing omission of \> 33% of study doses
10. Gr 5 toxicity

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, as follows: Grade 1 (mild/asymptomatic; no intervention); Grade 2 (moderate; minimal intervention); Grade 3 (severe/medically significant; hospitalization indicated; disabling); Grade 4 (life-threatening; urgent intervention required); or Grade 5 (fatal). Adverse events (AEs) were reported from clinical laboratory tests, vital sign and weight measurements, physical examinations, and any other medically indicated assessments, including participant interviews, from the time informed consent was signed through the end of the safety follow-up period. AEs were considered to be treatment-emergent adverse events (TEAEs) if they occurred or worsened in severity after the first dose of study treatment. TEAEs were considered treatment-related if the relationship to study drug was possibly, probably, or definitely related.

Appropriate imaging of the SYNB1891-injected tumor(s) and up to 5 target (noninjected) lesions was performed at baseline and every 2 cycles during the treatment period. Tumor response was assessed by the local investigator using RECIST 1.1 (Eisenhauer et al 2009). Per RECIST 1.1, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions (no evaluable disease); partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria.

IQVIA Biotech

Synlogic

AE documentation included duration (onset and resolution dates), severity using the NCI CTCAE (version 5.0), assessment of causality, seriousness, and whether specific action or therapy was required. In summaries, preferred terms are counted only once per participant at the maximum reported grade.

SYNB1891 was administered as an IT injection on Days 1, 8, and 15 of Cycle 1 and Day 1 of subsequent cycles.

Arm 1 Cohort 1: SYNB1891 Monotherapy (1 × 10^6 Live Cells)

Arm 1 Cohort 2: SYNB1891 Monotherapy (3 × 10^6 Live Cells)

Arm 1 Cohort 3: SYNB1891 Monotherapy (1 × 10^7 Live Cells)

Arm 1 Cohort 4: SYNB1891 Monotherapy (3 × 10^7 Live Cells)

Arm 1 Cohort 5: SYNB1891 Monotherapy (1 × 10^8 Live Cells)

Arm 1 Cohort 6: SYNB1891 Monotherapy (3 × 10^8 Live Cells)

SYNB1891 was administered as an IT injection on Days 1, 8, and 15 of Cycle 1 and Day 1 of subsequent cycles in combination with standard dose atezolizumab (1200 mg IV Q3W) on Day 1 of each cycle.

Arm 2 Cohort 1: SYNB1891 (1 × 10^7 Live Cells) + Atezolizumab

Arm 2 Cohort 2: SYNB1891 (3 × 10^7 Live Cells) + Atezolizumab

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Disease type

All participants who were enrolled, allocated to treatment, and received at least 1 dose of investigational product.

The study was terminated prematurely by the Sponsor prior to enrollment completion.

Because only 1 participant experienced a DLT (Grade 3 cytokine release syndrome in Arm 1 Cohort 6), no MTD could be reached.

Number of Participants With Dose-limiting Toxicity

Any TEAE

Maximum TEAE severity Grade 1

Maximum TEAE severity Grade 2

Maximum TEAE severity Grade 3

Maximum TEAE severity Grade 4

Maximum TEAE severity Grade 5

TEAE related to SYNB1891

TEAE related to atezolizumab

TEAE leading to treatment withdrawal

Number of Participants With Treatment-Emergent Adverse Events

All participants who received study drug and had an on-treatment response assessment (including "Not Evaluable") or who discontinued study before any response assessment was performed due to disease progression.

Number of Participants With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

SYNB1891 was administered as an intratumoral (IT) injection on Days 1, 8, and 15 of Cycle 1 and Day 1 of subsequent cycles.

SYNB1891 was administered as an IT injection on Days 1, 8, and 15 of Cycle 1 and Day 1 of subsequent cycles in combination with standard dose atezolizumab (1200 mg intravenously \[IV\] every 3 weeks \[Q3W\]) on Day 1 of each cycle.

Overall Study

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Carcinoma

Pancreatic Neoplasms

Recurrence

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Disease Attributes

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Patients receive siRNA-transfected peripheral blood mononuclear cells APN401 IV over 30 minutes on days 1, 29, and 57 in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

siRNA-transfected Peripheral Blood Mononuclear Cells APN401

Pierre Triozzi

This phase I trial studies the side effects and best dose of APN401 in treating patients with pancreatic cancer, colorectal cancer, or other solid tumors that have spread to other places in the body or have come back. APN401 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the toxicities and establish the safety of multiple infusions of small interfering ribonucleic acid (siRNA)-transfected peripheral blood mononuclear cells APN401 (APN401).

SECONDARY OBJECTIVES:

I. To determine the immunologic effects of multiple infusions of APN401. II. To document clinical response and survival.

OUTLINE:

Patients receive siRNA-transfected peripheral blood mononuclear cells APN401 intravenously (IV) over 30 minutes on days 1, 29, and 57 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery

Safety and Immunologic Activity of Multiple Infusions of APN401

Will be categorized by organ system and severity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events

Will be summarized as frequency counts and percentages.

Will be summarized as medians and ranges. The effects of treatment will be analyzed using paired t-tests or the non-parametric counterpart.

Exploratory survival plots will be estimated using the Kaplan Meier approach and median OS will be estimated if enough events occur.

Exploratory survival plots will be estimated using the Kaplan Meier approach and median PFS will be estimated if enough events occur.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Tolerability of SYNB1891 Injection Alone or in Combination With Atezolizumab in Adult Participants	NCT04167137	Metastatic Soli... Lymphoma	SYNB1891 Atezolizumab	18 Years -	Synlogic
APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery	NCT03087591	Metastatic Mali... Metastatic Soli... Recurrent Color... Recurrent Pancr... Recurrent Solid... Stage IV Colore... Stage IV Pancre... Stage IVA Color... Stage IVA Pancr... Stage IVB Color... Stage IVB Pancr... Unresectable So...	Laboratory Biom... siRNA-transfect...	18 Years -	Wake Forest University Health Sciences

Spots Global Cancer Trial Database for metastatic solid neoplasm