NCT04167137

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

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Synlogic · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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).

Conditions

• Metastatic Solid Neoplasm
• Lymphoma

Interventions

Type	Name	Description
DRUG	SYNB1891	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.
DRUG	Atezolizumab	Atezolizumab was administered in accordance with its recommended dose and schedule (1200 mg IV Q3W).

Timeline

• Start date: 2019-12-12
• Primary completion: 2021-12-09
• Completion: 2021-12-09
• First posted: 2019-11-18
• Last updated: 2024-05-03
• Results posted: 2024-05-03

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study