Oligometastatic Disease
Conditions
Keywords
Non-small cell lung cancer (NSCLC), Renal cell carcinoma (RCC), Adult
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 NSCLC or RCC
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.
Interventions
Sponsors
ImmuneSensor Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumor Effects | 18 months | Progression-free rate at 18 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events | Enrolment through end of study period (1 year, 3 months). AE data captured continually. | Occurrence of treatment-related adverse events |
| Anti-tumor Effects | 6 to 22 months | Progression-free at 8-week intervals from 6 months to 22 months |
| Quality of Life (QoL) | upon enrolment through end of study period (2 years) | Patient reported outcome on FACT-G questionnaire |
Countries
United States
Participant flow
Recruitment details
Study was terminated early by sponsor due to change in corporate strategy.
Participants by arm
| Arm | Count |
|---|---|
| Experimental Arm (800 mcg) PULSAR-ICI + IMSA101 (800 mcg) | 3 |
| Experimental Arm (1200 mcg) PULSAR-ICI + IMSA101 (1200 mcg) | 3 |
| Control Arm PULSAR - ICI | 0 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Early Study Termination | 1 | 2 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Experimental Arm (800 mcg) | Experimental Arm (1200 mcg) | Control Arm | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 0 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 0 / 0 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 0 / 0 |
Outcome results
Primary
Anti-tumor Effects
Progression-free rate at 18 months
Time frame: 18 months
Population: Data were not collected due to study termination prior to participants' assessment at the 18-month time point
Secondary
Anti-tumor Effects
Progression-free at 8-week intervals from 6 months to 22 months
Time frame: 6 to 22 months
Population: Data were not collected due to study termination prior to participants' assessment at the 18-month time point
Secondary
Anti-tumor Effects
Time to progression
Time frame: upon enrolment through end of study period (2 years)
Population: Data were not collected due to study termination prior to participants' assessment at the 18-month time point
Secondary
Anti-tumor Effects
Overall response rate, duration of response, progression-free survival
Time frame: upon enrolment through end of study period (2 years)
Population: Data were not collected due to study termination prior to participants' assessment at the 18-month time point
Secondary
Number of Participants With Treatment-related Adverse Events
Occurrence of treatment-related adverse events
Time frame: Enrolment through end of study period (1 year, 3 months). AE data captured continually.
Population: Zero patients enrolled to Control Arm during Safety Run In period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm (800 mcg) | Number of Participants With Treatment-related Adverse Events | 3 Participants |
| Experimental Arm (1200 mcg) | Number of Participants With Treatment-related Adverse Events | 3 Participants |
| Control Arm | Number of Participants With Treatment-related Adverse Events | 0 Participants |
Secondary
Quality of Life (QoL)
Patient reported outcome on FACT-G questionnaire
Time frame: upon enrolment through end of study period (2 years)
Population: Data were not collected due to study termination prior to participants' assessment at the 18-month time point