CLINICAL TRIAL / NCT05846659
Study of PULSAR-ICI +/- IMSA101 in Patients With Oligoprogressive Solid Tumor Malignancies
- Interventional
- Active
- NCT05846659
Contact Information
- Saleh Fadel
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
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.
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.
Gender
All
Age Group
18 Years and up
Accepting 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 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