Safety and Efficacy Study of IMSA101 in Refractory Malignancies

Inclusion Criteria

• •1. Signed informed consent and mental capability to understand the informed consent
• •2. Male or female patients \> 18 years of age
• •3. Histologically or cytologically documented locally advanced or metastatic solid tumor malignancies refractory to or otherwise ineligible for treatment with standard-of-care agents/regimens, including but not limited to:
• •* Malignant melanoma
• •* Hormone receptor negative breast cancer
• •* Gastro-esophageal cancer
• •* Non-small cell lung cancer
• •* Head and neck cancer
• •* Hepatoma
• •* Renal cell carcinoma
• •4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• •5. Evaluable or measurable disease as follows:
• •* A minimum of 3 RECIST-evaluable lesions: one that is suitable for injection and biopsied; one non-injected that will be biopsied for abscopal effect; and one measurable lesion that will be followed for response only.
• •* Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous injection only, including those lesions that are visible, palpable, or detectable by standard radiographic or ultrasound methods. Neither surgical procedures nor endoscopically-guided injections including those to endobronchial, endoluminal, or endosinusial spaces shall be allowed. While no anatomic locations are required or disallowed, lesions selected for intratumoral injection must, in the opinion of the investigator:
• •* Not be immediately adjacent to blood vasculature or other physiologic landmarks in such a way that will accrue undue safety risk to the patient
• •* Have longest diameter ≥ 10 mm and ≤ 50 mm
• •* Be fully efficacy evaluable per RECIST v1.1 criteria
• •6. Life expectancy \> 3 months (Phase I) and \> 6 months (Phase IIA)
• •7. ECG without evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the investigator
• •8. Acceptable organ and marrow function as defined below:
• •* Absolute neutrophil count \> 1,500 cells/μL
• •* Platelets \> 50,000 cells/μL
• •* Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• •* Aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤ 2.5 times ULN. If liver metastases are present, AST/ALT \< 5 times 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 times ULN
• •9. 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, e.g., greater than 45 years) must have a negative serum pregnancy test prior to first dose of study drug
• •10. Male and female patients with reproductive potential must agree to use two forms of highly effective contraception throughout the study
• •11. Phase I combination only: Demonstrated RECIST stable disease through ≥ 4 consecutive cycles of an approved PD-1 or PD-L1 targeted ICI with no Grade ≥ 3 CTCAE events considered by the investigator to be drug-related.