Study of PULSAR-ICI +/- IMSA101 in Patients With Oligometastatic NSCLC and RCC

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 Oligometastatic NSCLC and RCC

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 NSCLC or RCC

Study Overview

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

Detailed Description

Patients shall be enrolled in 2 treatment arms as follows:

1. 20 patients in the control arm (PULSAR-ICI alone)
2. 20 patients in the experimental arm (PULSAR-ICI + IMSA101)

Patients will be stratified by histology (NSCLC and RCC) in the randomized portion.

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).

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): 6
• 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
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44106
      • Louis Stokes Cleveland VA Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute, University of Utah
  • 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 NSCLC or RCC with radiographically documented presence of ≤ 6 metastatic lesions consistent with the diagnosis of "oligometastatic" disease
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 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 significant 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 aminotransferase (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 disease progression through programmed cell death ligand 1 (PD-L1 or PD-1)-targeted immunotherapy
2. Prior receipt of stimulator of interferon genes (STING) agonist
3. Prior receipt of therapeutic radiotherapy to the lesions intended for PULSAR treatment
4. Anti-cancer therapy, except pembrolizumab and nivolumab, within 4 weeks or < 5 half-lives of the first dose of study treatment
5. Existence of primary tumor that requires therapeutic treatment beyond the provided immune checkpoint inhibitor drug
6. Failure to recover, to Grade 1 or less, from clinically significant AEs due to prior anti-cancer therapy, as judged by the investigator
7. Previous life-threatening (Grade 4) immune-related adverse event (irAE)
8. Existence of actionable mutations that may be eligible for mutation-targeted drug that represents standard-of-care therapy
9. Presence of brain metastases
10. Baseline prolongation of QT/corrected QT (QTc) interval (QTc interval > 470)
11. 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
12. Women who are pregnant or breastfeeding
13. 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.; Radiation: PULSAR; 1st day of Cycles 1, 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
Active Comparator: Control Arm; PULSAR-ICI	Radiation: PULSAR; 1st day of Cycles 1, 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor Effects	Progression-free rate at 18 months	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-related Adverse Events	Occurrence of treatment-related adverse events	Enrolment through end of study period (1 year, 3 months). AE data captured continually.
Anti-tumor Effects	Progression-free at 8-week intervals from 6 months to 22 months	6 to 22 months
Anti-tumor Effects	Time to progression	upon enrolment through end of study period (2 years)
Anti-tumor Effects	Overall response rate, duration of response, progression-free survival	upon enrolment through end of study period (2 years)
Quality of Life (QoL)	Patient reported outcome on FACT-G questionnaire	upon enrolment through end of study period (2 years)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2023
• Primary Completion (Actual): September 16, 2024
• Study Completion (Actual): September 16, 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 (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Adult; Non-small cell lung cancer (NSCLC); Renal cell carcinoma (RCC)
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; 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: IMSA101-102

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