Phase 2 Randomized Clinical Trial Comparing the Safety and Efficacy of PULSAR-Integrated Radiotherapy + Pembrolizumab or Nivolumab Administered with or Without STING-Agonist IMSA101 in Patients with Oligoprogressive Solid Tumor Malignancies

ImmuneSensor Therapeutics Inc.14 sites in 1 country16 target enrollmentJuly 7, 2023

ConditionsOligoprogressive

InterventionsIMSA101 Immune checkpoint inhibitor PULSAR

Overview

Phase: Phase 2
Intervention: IMSA101
Conditions: Oligoprogressive
Sponsor: ImmuneSensor Therapeutics Inc.
Enrollment: 16
Locations: 14
Primary Endpoint: Anti-tumor effects
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Phase 2, open-label, multicenter, randomized study comparing the safety and efficacy of personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) combined with immune checkpoint inhibitor (ICI) immunotherapy (PULSAR-ICI) + IMSA101 and PULSAR-ICI alone in patients with oligoprogressive solid tumor malignancies after prior anti-cancer therapy.

Detailed Description

Patients shall be enrolled in 2 treatment arms as follows: 1. 15 patients in the control arm (PULSAR-ICI alone) 2. 30 patients in the experimental arm (PULSAR-ICI + IMSA101) PULSAR-ICI with or without IMSA101 treatment will be administered to the patients in Cycles 1, 2, and 3, and thereafter only standard of care ICI monotherapy will be administered to all patients. Each treatment cycle will be 28 days in duration for Cycles 1, 2 and 3, then per standard of care monotherapy thereafter based on the product labels of the prescribed ICI. The study will start with a safety run-in portion at 2 dose levels for the experimental arm, followed by a randomized portion for both treatment arms. The safety run-in shall employ a 3+3 safety run-in component. All patients will be followed throughout the study for drug tolerability and safety by collecting clinical and laboratory data, including adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 criteria, SAEs, concomitant medications, and vital signs. All patients will be assessed for anti-tumor efficacy at screening, prior to the end of Cycle 3, and at 8-week intervals thereafter based on radiographic assessments (all outcome measures per RECIST Version 1.1 and iRECIST). Tumor types and the corresponding treatment combinations to be evaluated will be identified prior to the first patient enrolled. All patients will continue to receive their assigned treatment throughout the study until the occurrence of disease progression (based on iRECIST), death, or other unacceptable treatment-related toxicity, or until the study is closed by the sponsor.

Registry

clinicaltrials.gov

Start Date

July 7, 2023

End Date

November 20, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

ImmuneSensor Therapeutics Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female patients ≥ 18 years of age
•Signed informed consent and mental capability to understand the informed consent
•Histologically or cytologically documented solid tumor malignancies demonstrating new progression through prior anti-cancer therapy, with a prior 2 months of clinical stability (with at least Stable Disease), with radiographically documented presence of ≤ 6 metastatic lesions consistent with the diagnosis of "oligoprogressive" disease that are technically amenable to PULSAR
•Patient's disease must be evaluable per RECIST Version 1.1
•All metastatic lesions amenable to administration of radiotherapy, at the discretion of the investigator
•Must have at least one single pre-defined progressing lesion/lesion site (longest diameter ≥ 10 mm and ≤ 50 mm) suitable for intra-tumoral injection
•Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
•Electrocardiogram (ECG) without evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the investigator
•Acceptable organ and marrow function as defined below:
•Absolute neutrophil count (ANC) \> 1,500 cells/μL

Exclusion Criteria

•Prior receipt of stimulator of interferon genes (STING) agonist
•Prior receipt of therapeutic radiotherapy to all progressive lesions intended for PULSAR treatment
•Anti-cancer therapy, except pembrolizumab and nivolumab, within 4 weeks or \< 5 half-lives of the first dose of study treatment
•Existence of primary tumor that requires therapeutic treatment beyond the provided immune checkpoint inhibitor drug
•Failure to recover, to Grade 1 or less, from clinically significant AEs due to prior anti-cancer therapy, as judged by the investigator
•Previous life-threatening (Grade 4) immune-related adverse event (irAE)
•Known untreated brain metastases or treated brain metastases that have not been stable (scan showing no worsening of central nervous system \[CNS\] lesion\[s\] and no requirement of corticosteroids) ≥ 4 weeks prior to study enrollment
•Existence of actionable mutations that are eligible for a mutation-targeting drug that represents standard-of-care
•Baseline prolongation of QT/corrected QT (QTc) interval (QTc interval \> 470)
•Uncontrolled intercurrent illness (including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations) that in the opinion of the investigator would limit compliance with study requirements