Study of LP-184 in Patients with Advanced Solid Tumors

Patient Inclusion Criteria:

1. ≥18 years of age at the time of consent

2. Provided signed written ICF and voluntary consent prior to any mandatorystudy-specific procedures, sampling, and analyses.

3. Have a histologically or cytologically documented advanced solid tumor that hasrelapsed from or is refractory to standard treatment, or for which no standardtreatment is available. Note: patients with certain tumor types such as those with relatively highprevalence of DDR gene alterations and/or PTGR1 over expression (e.g., triplenegative breast cancer, lung, prostate, ovarian, pancreatic, bladder, and GBM) maybe 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 asapplicable. Note: patients without measurable disease may be eligible, following discussion withthe investigator and the sponsor, if the patient presents with non-measurable butevaluable 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 orinvolvement of liver in the disease process.

• Total serum bilirubin ≤1.5 x ULN or <5 x ULN if secondary to Gilbert's syndromeor documented liver metastases or involvement of liver in the disease process. Renal Function

• Serum creatinine clearance ≥60 mL/min either measured or calculated usingstandard Cockcroft-Gault formula.

• Serum electrolyte (potassium, calcium, and magnesium) levels within the normalreference 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 achievehemoglobin ≥8 g/dL is acceptable. For those patients undergoing RBCtransfusion, hemoglobin must be evaluated at least 14 days after the last RBCtransfusion).

• Platelet count ≥100,000/μL (assessed ≥7 days following last platelettransfusion in patients with thrombocytopenia requiring platelets). Blood clotting function:

• INR and aPTT ≤1.5 x ULN. Study patients on therapeutic doses of anticoagulationmedication must have INR and/or aPTT ≤ the upper limit of the therapeutic rangefor intended use.

8. Women of childbearing potential (WOCBP) must have a negative serum or urinepregnancy test within 3 days of first dose of LP-184. A woman is of child-bearingpotential 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 noirregular menses or spotting) in the absence of any medication which induces amenopausal state and has documented ovarian failure by serum estradiol andfollicle-stimulating hormone levels within the institutional laboratorypostmenopausal range).

9. WOCBP or must agree to use highly effective contraceptive methods and avoid eggdonation 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 methodsand avoid sperm donation during the study treatment and for 3 months after the lastdose of LP-184. A man is of child-producing potential unless he has had a bilateralvasectomy with documented aspermia or a bilateral orchiectomy.

11. Is willing to provide archived samples (blocks and/or slides) for comprehensive DDRgenomic analyses and/or PTGR1 expression profiling and/or other genomic alterationsif the patient has a PR/CR.

12. Regarding brain metastases, based on screening contrast brain MRI, patients musthave 1of the following:

• No evidence of brain metastases

• Untreated brain metastases not requiring immediate local therapy. For patientswith untreated CNS lesions >2.0 cm on screening contrast brain MRI, discussionwith and approval from the Medical Monitor is required prior to enrollment.

• Previously treated brain metastases that are either stable for at least 4 weekssince last treatment or progressed since prior local CNS therapy and notrequiring immediate re-treatment with local therapy in the opinion of theinvestigator.

Patient Exclusion Criteria:

1. Exposure to anti-cancer therapy within 2 weeks or within at least 5 half-lives ofthe anticancer agent whichever is shorter; or 4 weeks from anybiologics/immunotherapies or any investigational therapy prior to the first dose ofLP-184. Note: Low dose steroids (oral prednisone or equivalent ≤20 mg/day, except patientswith GBM), localized non-CNS radiotherapy, previous hormonal therapy withluteinizing hormone-releasing hormone agonists for prostate cancer and treatmentwith bisphosphonates and RANKL inhibitors are not criteria for exclusion if suchtherapy has not been changed within 4 weeks before LP-184 treatment.

2. Any history of retinopathy and/or macular degeneration (without specifications orgrades).

3. Has received radiation within 4 weeks of Cycle 1 Day 1. Unless the tumor at the siteof treatment continues to increase in size after the patient has completedradiotherapy treatment.

4. Infection requiring antibiotics, antivirals, or antifungals within 1 week prior tofirst dose of study drug, unless such infection is adequately controlled (defined asexhibiting no ongoing signs/symptoms related to the infection and with clinicalimprovement). In the case of prophylactic use of these agents, discussion with theMedical Monitor is required prior to enrollment.

5. Hepatitis B and/or hepatitis C infection (as detected by positive testing forhepatitis B surface antigen [HbsAg] or antibody to hepatitis C virus withconfirmatory testing) or known seropositivity for or history of active viralinfection with human immunodeficiency virus (HIV).

6. Are pregnant or breastfeeding. (NOTE: breast milk cannot be stored for future usewhile the mother is being treated on study).

7. Have clinically significant cardiac disease including:

• New York Heart Association Class IV heart failure.

• Myocardial infarction or stroke ≤3 months prior to the first dose of LP-184.

• Unstable angina within ≤12 weeks prior to the first dose of LP-184 unless theunderlying disease has been corrected by procedural intervention e.g., stent,bypass.

• Severe aortic stenosis.

• Uncontrolled arrhythmia. Sponsor approval of patients with arrhythmia isrequired.

• QTc >470 ms by Fredericia criteria.

• Congenital long QT syndrome, or a QT interval corrected by Fridericia's formula (QTcF) >470 ms (average of triplicate ECGs) at Screening and/or on Cycle 1 Day 1 (pre-dose) except for a documented bundle branch block or unless secondary topacemaker. In the case of a documented bundle branch block or a pacemaker,discussion with the medical monitor is required prior to enrollment.

8. Have clinically significant AEs that have not returned to baseline or ≤Grade 1 basedon NCI-CTCAE prior to first dose of study drug, unless approved by the sponsor.Patients with chronic Grade 2 toxicities may be eligible per the discretion of theinvestigator and sponsor (e.g., Grade 2 chemotherapy-induced neuropathy, alopecia,or hypothyroidism from prior immunotherapy treatment).

9. Have had major surgery (requiring general anesthesia) within ≤4 weeks of first doseof LP-184.

10. Have any other serious medical condition which, in the opinion of the investigator,would preclude the patient from study participation.

11. Have clinically active brain metastases, defined as untreated and symptomatic, orrequiring therapy with steroids at a dose > 2 mg of dexamethasone or equivalent oranticonvulsants to control associated symptoms. Patients with treated brainmetastases that are no longer symptomatic and who require no treatment with steroidsmay be included in the study if they have recovered from the acute toxic effect ofradiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brainradiotherapy and study enrollment (1 week for stereotactic radiotherapy).

12. For patients with suspected or known CNS metastatic disease, based on screeningbrain MRI, patients must not have: Any untreated brain lesions >2.0 cm in size unless Medical Monitor approvedenrollment. Ongoing use of systemic corticosteroids for control of symptoms of brain metastasesat a total daily dose of >2 mg of dexamethasone (or equivalent). Patients on a chronic stable dose of ≤2 mg total daily of dexamethasone (orequivalent) are eligible with discussion and approval by the medical monitor. (Note:this is not applicable to patients with GBM). Any brain lesion thought to require immediate local therapy, including (but notlimited to) a lesion in an anatomic site where an increase in size or possibletreatment-related edema may pose a risk to the patient (e.g., brain stem lesions).Patients who underwent local treatment for such lesions identified by screeningcontrast brain MRI may still be eligible based on criteria described under CNSinclusion criteria described above.

• Known or suspected leptomeningeal disease as documented by the investigator.

13. Male patients with partners currently pregnant, or male patients able to fatherchildren, and female patients of childbearing potential who are unwilling or unableto use highly effective methods of contraception as outlined in this protocol forthe duration of the study and for at least 3 months (male) or 6 months (female)after last dose of study drug