A Study of SPX-303, a Bispecific Antibody Targeting LILRB2 and PD-L1 in Patients With Solid Tumors

Inclusion Criteria:

1. Males and females ≥18 years of age who comprehend, are not incarcerated, are willingand able to provide consent by signing an ICF, and able to comply with scheduledvisits, treatment schedule, and laboratory tests, including other requirements forthe study

2. Histologically or cytologically documented locally advanced or metastatic solidtumor malignancy

3. Patients who have progressed on or after prior therapy and who are not eligible foravailable treatment options

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

5. Has at least 1 measurable lesion per RECIST 1.1 criteria

6. Recovery from previous treatment related adverse events (TRAEs) to allow safetyevaluations of SPX-303. Previous TRAEs include adverse drug reactions, andconsequences of radiation, surgery, and other therapeutic modalities

7. Adequate hepatic function; bilirubin ≤1.5x upper limit of normal (ULN) (except forpatients with Gilbert syndrome: ≤ 3xULN), aspartate aminotransferase (AST), andalanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver metastases present).

8. Adequate renal function as calculated (e.g. Cockroft Gault) creatine clearance (CrCl) ≥ 30 mL/min or 24-hour urine CrCl ≥ 30 mL/min.

9. Adequate hematological function: absolute neutrophil count (ANC) ≥1 x 10^9/L;platelets ≥75 x 10^9/L, hemoglobin ≥9 g/dL.

10. Patients with well controlled HIV infection (ie CD4+ count >350 cells/uL and viralcopies less than 400/mL after at least 4 weeks of ART) are eligible for the trial.

11. Adequate coagulation function: INR, PT and aPPT ≤ 1.5x ULN except for patients onanti-coagulation as long as PT, aPPT, or INR are within intended range.

12. Adequate cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥ 45% bymulti-gated acquisition (MUGA) or echocardiography (ECHO) scan.

13. Fridericia-corrected QT interval (QTcF) ≤480 msec.

14. Women of childbearing potential must have a negative pregnancy test and must agreeto use of 2 different methods of acceptable contraception from screening until 4months after the last dose of study drug. Acceptable methods of contraception aredefined as those that result, alone or in combination, in a low failure rate (ie,less than 1% per year) when used consistently and correctly, such as surgicalsterilization, an intrauterine device, hormonal contraception in combination with abarrier method or abstinence).

15. Males who are sexually active with a female partner of childbearing potential mustagree to use a barrier contraception (eg, condom with spermicidalfoam/gel/film/cream/suppository) from screening until 4 months following the lastdose of study drug, in addition to their female partner using either an intrauterinedevice or hormonal contraception and continuing until 4 months following the lastdose of study drug. This criterion may be waived for male patients who have had avasectomy >6 months before signing the ICF.

Exclusion Criteria:

1. History of prior malignancy, except for adequately treated in situ cancer, basalcell, or squamous cell skin cancer, or other cancers (eg, breast, prostate) forwhich the patient has been disease free for at least 3 years. Prostate cancerpatients on active surveillance are eligible.

2. Active brain or leptomeningeal metastasis. Except patients with known brainmetastases if they have been treated and MRI shows no evidence of progression for atleast 8 weeks and require less than 10 mg/day prednisone/prednisolone or equivalent.

3. Treatment with anti neoplastic therapy ≤ 28 days or ≤ 5× elimination half life,whichever is shorter, before the first dose of study drug.

4. Major surgery requiring general anesthesia ≤ 28 days prior to dosing.

5. History of permanent discontinuation of prior IO therapy due to irAE.

6. Prior treatment targeting ILT2 and/or ILT4 or targeting HLA G.

7. Live or live attenuated vaccine ≤ 28days prior to dosing.

8. Immunosuppressive systemic medication, except topical corticosteroids or systemiccorticosteroids at a dose level of ≤ 10 mg/d of prednisone/prednisolone orequivalent. Note: patients with adrenal insufficiency requiring hormonal replacementmay receive higher dose of steroids.

9. Prior solid organ or bone marrow transplantation (except cornea transplantation).

10. History of clinically significant cardiovascular events (e.g. DVT ≤ 6 months, PE ≤ 12 months, MI or hospitalization for CHF ≤ 12 months, bleeding disorder or bleedingevent ≤ 6 months, current clinically significant arrhythmia or unstable anginapectoris, current uncontrolled history of cerebrovascular accident in the past 6months, current uncontrolled hypertension).