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 Non-Small Cell Lung Cancer and Renal Cell Carcinoma
the primary objective:
To establish safe recommended Phase 2 doses (RP2Ds) of IMSA101. Patients older than 18 years old with histologically or cytologically documented locally advanced or metastatic solid tumor malignancies refractory to or otherwise ineligible for treatment with standard of care agents/regimens are enrolled. IMSA101 at 100, 200, 400, 800, and 1200 mcg in 1 mL total volume are administered as monotherapy to the patients by intra-tumoral injection every week for 3 weeks in Cycle 1 (Days 1, 8, and 15) followed by every other week from Cycles 2 onwards (Days 1 and 15). For combination treatment regimen, IMSA101 up to 800, 1200, 2400, 3600, and 4800 mcg in 1 mL total volume + current ICI therapy administered according to the product label is administered to the patients by intra-tumoral injection. Dose priming was applied in Cycle 1 Day 1 (C1D1) for doses of 2400-4800 mcg.
Other Urinary
PULSAR
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Matthew Deek
- Principal Investigator
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
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.