Study of LP-184 in Patients With Advanced Solid Tumors

Inclusion Criteria

• •1. ≥18 years of age at the time of consent
• •2. Provided signed written ICF and voluntary consent prior to any mandatory study-specific procedures, sampling, and analyses.
• •3. Have a histologically or cytologically documented advanced solid tumor that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available.
• •Note: patients with certain tumor types such as those with relatively high prevalence of DDR gene alterations and/or PTGR1 over expression (e.g., triple negative breast cancer, lung, prostate, ovarian, pancreatic, bladder, and GBM) may be preferentially enrolled in Phase 1a.
• •4. ECOG performance status 0-1 or Karnofsky performance scale \>60 for GBM patients.
• •5. Patients must have measurable disease per RECIST 1.1 or RANO 2.0 criteria as applicable.
• •Note: patients without measurable disease may be eligible, following discussion with the investigator and the sponsor, if the patient presents with non-measurable but evaluable disease of any size unequivocally attributable to advanced solid tumor.
• •6. Patients must have life expectancy \>3 months.
• •7. Adequate organ function at screening defined as:
• •Liver Function
• •* AST, ALT ≤3 x ULN or \<5 x ULN in cases of documented liver metastases or involvement of liver in the disease process.
• •* Total serum bilirubin ≤1.5 x ULN or \<5 x ULN if secondary to Gilbert's syndrome or documented liver metastases or involvement of liver in the disease process.
• •Renal Function
• •* Serum creatinine clearance ≥60 mL/min either measured or calculated using standard Cockcroft-Gault formula.
• •* Serum electrolyte (potassium, calcium, and magnesium) levels within the normal reference range (may be supplemented according to institutional standard).
• •Bone Marrow Function:
• •* ANC ≥1500/μL.
• •* Hemoglobin ≥8 g/dL (The use of transfusion or other intervention to achieve hemoglobin ≥8 g/dL is acceptable. For those patients undergoing RBC transfusion, hemoglobin must be evaluated at least 14 days after the last RBC transfusion).
• •* Platelet count ≥100,000/μL (assessed ≥7 days following last platelet transfusion in patients with thrombocytopenia requiring platelets).
• •Blood clotting function:
• •\- INR and aPTT ≤1.5 x ULN. Study patients on therapeutic doses of anticoagulation medication must have INR and/or aPTT ≤ the upper limit of the therapeutic range for intended use.
• •8. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 3 days of first dose of LP-184. A woman is of child-bearing potential unless she:
• •* has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy;
• •* is age ≥60 years and is amenorrhoeic; or
• •* is age \<60 years and has been amenorrhoeic for ≥12 months (including no irregular menses or spotting) in the absence of any medication which induces a menopausal state and has documented ovarian failure by serum estradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range).
• •9. WOCBP or must agree to use highly effective contraceptive methods and avoid egg donation during the study treatment and for 6 months after the last dose of LP-184.
• •10. Men of reproductive potential agree to use highly effective contraceptive methods and avoid sperm donation during the study treatment and for 3 months after the last dose of LP-184. A man is of child-producing potential unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.
• •11. Is willing to provide archived samples (blocks and/or slides) for comprehensive DDR genomic analyses and/or PTGR1 expression profiling and/or other genomic alterations if the patient has a PR/CR.
• •12. Regarding brain metastases, based on screening contrast brain MRI, patients must have 1of the following:
• •* No evidence of brain metastases
• •* Untreated brain metastases not requiring immediate local therapy. For patients with untreated CNS lesions \>2.0 cm on screening contrast brain MRI, discussion with and approval from the Medical Monitor is required prior to enrollment.
• •* Previously treated brain metastases that are either stable for at least 4 weeks since last treatment or progressed since prior local CNS therapy and not requiring immediate re-treatment with local therapy in the opinion of the investigator.
• •• Known or suspected leptomeningeal disease as documented by the investigator.
• •13. Male patients with partners currently pregnant, or male patients able to father children, and female patients of childbearing potential who are unwilling or unable to use highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 3 months (male) or 6 months (female) after last dose of study drug