Study of PULSAR-ICI +/- IMSA101 in Patients With Oligoprogressive Solid Tumor Malignancies

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

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.

Study Overview

• Status: Terminated
• Conditions: Oligoprogressive
• Intervention / Treatment: Drug: IMSA101; Drug: Immune checkpoint inhibitor; Radiation: PULSAR

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92618
      • City of Hope Orange County Lennar Foundation Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital/Dana Farber Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44106
      • Louis Stokes Cleveland VA Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age
2. Signed informed consent and mental capability to understand the informed consent
3. 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
4. Patient's disease must be evaluable per RECIST Version 1.1
5. All metastatic lesions amenable to administration of radiotherapy, at the discretion of the investigator
6. Must have at least one single pre-defined progressing lesion/lesion site (longest diameter ≥ 10 mm and ≤ 50 mm) suitable for intra-tumoral injection
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
8. Electrocardiogram (ECG) without evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the investigator

9. Acceptable organ and marrow function as defined below:

   • Absolute neutrophil count (ANC) > 1,500 cells/μL
   • Platelets > 50,000 cells/μL
   • Total bilirubin ≤ 1.5 times (×) the upper limit of normal (ULN)
   • Aspartate aminotransferase (AST)/alanine aminotransaminase (ALT) ≤ 2.5 × ULN. If liver metastases are present, AST/ALT < 5 × ULN
   • Serum creatinine < 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula
   • Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 × ULN
10. Women of child-bearing potential (defined as a female who has experienced menarche and who has not undergone successful surgical sterilization [hysterectomy, bilateral salpingectomy, or bilateral oophorectomy]) or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months with an appropriate clinical profile at the appropriate age, eg, greater than 45 years) must have a negative serum pregnancy test prior to first dose of study treatment
11. Male and female patients with reproductive potential must agree to use two forms of highly effective contraception throughout the study

Exclusion Criteria:

1. Prior receipt of stimulator of interferon genes (STING) agonist
2. Prior receipt of therapeutic radiotherapy to all progressive lesions intended for PULSAR treatment
3. Anti-cancer therapy, except pembrolizumab and nivolumab, within 4 weeks or < 5 half-lives of the first dose of study treatment
4. Existence of primary tumor that requires therapeutic treatment beyond the provided immune checkpoint inhibitor drug
5. Failure to recover, to Grade 1 or less, from clinically significant AEs due to prior anti-cancer therapy, as judged by the investigator
6. Previous life-threatening (Grade 4) immune-related adverse event (irAE)
7. 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
8. Existence of actionable mutations that are eligible for a mutation-targeting drug that represents standard-of-care
9. Baseline prolongation of QT/corrected QT (QTc) interval (QTc interval > 470)
10. 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
11. Women who are pregnant or breastfeeding
12. Sponsor reserves the right to exclude any patient from the study on the basis of pre-study medical histories, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; PULSAR-ICI + IMSA101	Drug: IMSA101; Intra-tumoral administration once weekly for the first three weeks of Cycle 1 (Days 1, 8 and 15) and then on Day 1 of Cycles 2 and 3.; Drug: Immune checkpoint inhibitor; 1st infusion on Cycle 1 Day 2, and then thereafter as per product label.; Other Names: pembrolizumab; nivolumab; Radiation: PULSAR; 1st day of Cycles 1, 2 and 3.
Active Comparator: Control Arm; PULSAR-ICI	Drug: Immune checkpoint inhibitor; 1st infusion on Cycle 1 Day 2, and then thereafter as per product label.; Other Names: pembrolizumab; nivolumab; Radiation: PULSAR; 1st day of Cycles 1, 2 and 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor Effects	Progression-free rate at 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Occurrence of treatment-related adverse events and SAEs	8 months
Anti-tumor Effects	Progression-free at 8-week intervals from 6 months to 8 months.	6 to 8 months
Anti-tumor Effects	Time-to-progression (TTP)	upon enrolment through end of study period (8 months)
Anti-tumor Effects	Overall response rate, duration of response, progression-free survival	upon enrolment through end of study period (8 months)
Functional Assessment of Cancer Therapy - General (FACT-G) Quality of Life (QoL)	The Functional Assessment of Cancer Therapy - General (FACT-G) is a patient-reported outcome (PRO) assessing health-related quality of life (HRQoL) in individuals with cancer across physical, social/family, emotional, and functional domains. The FACT-G (Version 4) contains 27 items across four subscales. Each item uses a 0-4 Likert scale (0 = Not at all, 4 = Very much), with some items reverse-scored so that higher scores always indicate better quality of life. Physical Well-Being (PWB) - 7 items, score range 0-28 (higher = better physical well-being. Social/Family Well-Being (SWB) - 7 items, score range 0-28 (higher = better social/family well being) Emotional Well-Being (EWB) - 6 items, score range 0-24 (higher = better emotional well-being) Functional Well-Being (FWB) - 7 items, score range 0-28 (higher = better functional well being) Scores provided show average baseline and average post-baseline comparison scores for all patient who completed the FACT-G questionnaire on trial	upon enrolment through end of study period (8 months)

Collaborators and Investigators

• Sponsor: ImmuneSensor Therapeutics Inc.
• Investigators: Study Director: Patrick Widhelm, ImmuneSensor Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2023
• Primary Completion (Actual): November 20, 2024
• Study Completion (Actual): November 20, 2024

Study Registration Dates

• First Submitted: April 27, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Adult; Oligoprogressive solid tumor malignancies
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Amino Acids, Peptides, and Proteins; Proteins; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Polysaccharides; Glucans; Dextrans; Nivolumab; Immune Checkpoint Inhibitors; pembrolizumab; DEAE-Dextran
• Other Study ID Numbers: IMSA101-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No