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

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