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

NCT ID: NCT05846659

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-07

Study Completion Date

2024-11-20

Brief Summary

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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

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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.

Conditions

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Oligoprogressive

Keywords

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Oligoprogressive solid tumor malignancies Adult

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental Arm

PULSAR-ICI + IMSA101

Group Type EXPERIMENTAL

IMSA101

Intervention Type DRUG

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.

Immune checkpoint inhibitor

Intervention Type DRUG

1st infusion on Cycle 1 Day 2, and then thereafter as per product label.

PULSAR

Intervention Type RADIATION

1st day of Cycles 1, 2 and 3.

Control Arm

PULSAR-ICI

Group Type ACTIVE_COMPARATOR

Immune checkpoint inhibitor

Intervention Type DRUG

1st infusion on Cycle 1 Day 2, and then thereafter as per product label.

PULSAR

Intervention Type RADIATION

1st day of Cycles 1, 2 and 3.

Interventions

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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.

Intervention Type DRUG

Immune checkpoint inhibitor

1st infusion on Cycle 1 Day 2, and then thereafter as per product label.

Intervention Type DRUG

PULSAR

1st day of Cycles 1, 2 and 3.

Intervention Type RADIATION

Other Intervention Names

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pembrolizumab nivolumab

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ImmuneSensor Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patrick Widhelm

Role: STUDY_DIRECTOR

ImmuneSensor Therapeutics

Locations

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City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California, United States

Site Status

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Brigham and Women's Hospital/Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Louis Stokes Cleveland VA Medical Center

Cleveland, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine Medical Center

Houston, Texas, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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IMSA101-103

Identifier Type: -

Identifier Source: org_study_id