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

• ClinicalTrials.gov Identifier: NCT05846659
• Recruitment Status: Recruiting
• First Posted: May 6, 2023
• Last Update Posted: February 28, 2024
• Sponsor: ImmuneSensor Therapeutics Inc.
• Information provided by (Responsible Party): ImmuneSensor Therapeutics Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Oligoprogressive	Drug: IMSA101; Drug: Immune checkpoint inhibitor; Radiation: PULSAR	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 7, 2023
• Estimated Primary Completion Date: November 2025
• Estimated Study Completion Date: February 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Anti-tumor effects [ Time Frame: assessment at 12 months ]
   Progression-free rate at 12 months

Secondary Outcome Measures :

1. Safety and tolerability [ Time Frame: upon enrolment through end of study period (2 years) ]
   Occurrence of treatment-related adverse events and SAEs
2. Anti-tumor effects [ Time Frame: 6 to 22 months ]
   Progression-free at 8-week intervals from 6 months to 22 months
3. Anti-tumor effects [ Time Frame: upon enrolment through end of study period (2 years) ]
   Time-to-progression (TTP)
4. Anti-tumor effects [ Time Frame: upon enrolment through end of study period (2 years) ]
   Overall response rate, duration of response, progression-free survival
5. Quality of life (QoL) [ Time Frame: upon enrolment through end of study period (2 years) ]
   Patient-reported outcome using FACT-G

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Patrick Widhelm; 830-730-8176; pwidhelm@immunesensor.com

Locations

United States, California

City of Hope Orange County Lennar Foundation Cancer Center; Recruiting

Irvine, California, United States, 92618

Contact: Jenny P Sanchez jesanchez@coh.org

Contact: Kat Irenze, RN 949-671-4055 kirenze@coh.org

Principal Investigator: Percy Lee, MD

USC/Norris Comprehensive Cancer Center; Recruiting

Los Angeles, California, United States, 90033

Contact: Sarah Chevalier, RN Sarah.chevalier@med.usc.edu

Contact: Andrew Zeng 323-865-0490 Andrew.zeng@med.usc.edu

Principal Investigator: Jason Ye, MD

UCLA; Not yet recruiting

Los Angeles, California, United States, 90095

Contact: Talia Oughourlian 310-869-6889 Toughourlian@mednet.ucla.edu

Principal Investigator: Drew Moghanaki, MD

United States, Illinois

Northwestern Memorial Hospital; Recruiting

Chicago, Illinois, United States, 60611

Contact: Elise Catherine Lemp Elise.lemp@northwestern.edu

Principal Investigator: Devalingam Mahalingam, MB BCh, BAO, PhD

United States, Massachusetts

Brigham and Women's Hospital/Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Caitlyn Kwan caitlyn_kwan@dfci.harvard.edu

Principal Investigator: Mai Anh Huynh, MD

United States, Missouri

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Jennifer Traber traber@wustl.edu

Principal Investigator: Greg Vlacich, MD

United States, New York

Montefiore Medical Center; Recruiting

Bronx, New York, United States, 10461

Contact: Adel Zakharia 718-405-8232 adel.zakharia@einsteinmed.edu

Contact: Alla Ahmed alahmed@montefiore.org

Principal Investigator: Nitin Ohri, MD

United States, Ohio

Louis Stokes Cleveland VA Medical Center; Recruiting

Cleveland, Ohio, United States, 44106

Contact: Megan Tyler 216-231-3241 Megan.Tyler2@va.gov

Principal Investigator: Aryavarta Kumar, MD

United States, Texas

UT Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

Contact: Ahmed Gul Ahmed.Gul@UTsouthwestern.edu

Contact: Sarah Neufelf 214-648-1836 sarah.hardee@utsouthwestern.edu

Principal Investigator: Mona Arbab, MD

Sponsors and Collaborators

ImmuneSensor Therapeutics Inc.

Investigators

• Study Director: Patrick Widhelm; ImmuneSensor Therapeutics

More Information

• Responsible Party: ImmuneSensor Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT05846659
• Other Study ID Numbers: IMSA101-103
• First Posted: May 6, 2023
• Last Update Posted: February 28, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ImmuneSensor Therapeutics Inc.:

Oligoprogressive solid tumor malignancies; Adult

Additional relevant MeSH terms:

Neoplasms; Pembrolizumab; Nivolumab; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action