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

Oligometastatic Disease Clinical Trial

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 Oligometastatic NSCLC and RCC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05846646
• Other study ID #: IMSA101-102
• Status: Recruiting
• Phase: Phase 2
• Start date: June 28, 2023
• Est. completion date: February 2026

Study information

• Verified date: February 2024
• Source: ImmuneSensor Therapeutics Inc.
• Contact: Patrick Widhelm
• Phone: 830-730-8176
• Email: pwidhelm[@]immunesensor.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 NSCLC or RCC

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: February 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Oligometastatic Disease

Intervention

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

Radiation:
• PULSAR
1st day of Cycles 1, 2 and 3.

Locations

Country	Name	City	State
United States	Louis Stokes Cleveland VA Medical Center	Cleveland	Ohio
United States	City of Hope Orange County Lennar Foundation Cancer Center	Irvine	California
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
ImmuneSensor Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-tumor effects	Progression-free rate at 18 months	18 months
Secondary	Safety and tolerability	Occurrence of treatment-related adverse events	upon enrolment through end of study period (2 years)
Secondary	Anti-tumor effects	Progression-free at 8-week intervals from 6 months to 22 months	6 to 22 months
Secondary	Anti-tumor effects	Time to progression	upon enrolment through end of study period (2 years)
Secondary	Anti-tumor effects	Overall response rate, duration of response, progression-free survival	upon enrolment through end of study period (2 years)
Secondary	Quality of life (QoL)	Patient reported outcome on FACT-G questionnaire	upon enrolment through end of study period (2 years)