First in Human Phase 1 Study of AG01 Anti-Progranulin/GP88 Antibody in Advanced Solid Tumor Malignancies

Inclusion Criteria:

1. Signed informed consent/authorization is obtained prior to conducting anystudy-specific screening procedures.
2. 18 years of age or older.
3. Histologic or cytologic diagnosis of advanced cancer.
4. Radiographic evidence of at least 1 measurable metastatic lesion per RECIST 1.1criteria.
5. Patients with relapsed/refractory solid tumor malignancies who failed one or morestandard chemotherapy or targeted therapy regimens per SOC guidelines such as NCCNguidelines and for whom no standard therapy exists (Phase 1A). No GP88 expressionpre-required for phase 1A.
6. For phase 1B, patients must have GP88 tissue tumor tissue expression of 1+, 2+ or 3+by IHC, archival tumor tissue will be used whenever possible. If no archival tissue isavailable, subject will be asked to consent to a study specific tumor biopsy for GP88testing (phase1B). Patients who do not have archival tissue available for the doseexpansion cohort (1B) will not be exposed to significant risk procedure to obtaintissue and may still be eligible for the study, after discussion with the Sponsor andMedical Monitor.
7. At least 4 weeks after the last dose of chemotherapy or radiation therapy; 6 weeks formitoxantrone or mitomycin therapy.
8. ECOG performance status must be ≤2 (Appendix A).
9. Adequate hepatic, renal, and bone marrow function: Absolute neutrophil count ≥ 1,000/uL Platelets ≥ 100,000/µL Total bilirubin WNL perInstitution ULN AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional ULN Creatinine ≤1.2 mg/dLClearance ≥50ml/min (Cockcroft-Gault)
10. All study participants (male and female) with reproductive potential must practicehighly effective methods of contraception (failure rate <1% annually) while on thisstudy and for 90 days after completion of study therapy.
11. Men and women of all ethnic groups are eligible for this trial.
12. Females at reproductive age must have a negative urine pregnancy test prior to entryto this study.
13. Males with partners at reproductive age must use highly effective birth controlmethods to prevent partners' pregnancy while on study and for 90 days after completionof study treatments.
14. Life expectancy is greater than 12 weeks.
15. Subjects with triple negative breast cancer (TNBC) cohort must have received 1 or morestandard of care (SOC) or targeted therapies for metastatic TNBC. If PD(L)1-positive,must have received a combination of chemotherapy and a PD (L)-1 agent (Atezolizumab orPembrolizumab), unless not a candidate for these therapies. If gBRCA 1 or 2 mutationis present, must have received SOC therapies including a PARPi, unless not a candidatefor these therapies. is FDA approved for treatment of advanced TNBC. Prior exposure toSacituzumab Govitecan ADC therapy does not preclude eligibility in the current study.
16. Subjects with Cohort 2-Breast Cancer ER and/or PR positive, hormone-resistant breastcancer who received 1 or more hormonal (HT) therapies or HT/CD4/6 kinase inhibitor orHT/MTOR inhibitor for treatment of metastatic breast cancer are eligible. If the tumorhas known PIK3CA mutation, HT/Alpelisib combination should be considered unless not acandidate for this therapy.
17. Subjects with metastatic/recurrent NSCLCA who failed 2 or more SOC therapies,including platinum-based chemotherapy and an anti-PD (L) -1 agent (sequentially orconsecutively). Patients with sensitizing mutations/alterations/rearrangements areeligible if received 1 or more SOC agent/s targeting these mutations unless not acandidate for these therapies.
18. Mesothelioma patients who have received at least 1 SOC therapy formetastatic/recurrent mesothelioma per NCCN recommendations or not a candidate for SOCtherapy.

Exclusion Criteria:

1. Uncontrolled inter-current illness including, but not limited to, symptomaticcongestive heart failure, unstable angina pectoris, cardiac arrhythmias not wellcontrolled with medication, myocardial infarction within the previous 6 months, orpsychiatric illness/social situations that would limit compliance with studyrequirements.
2. Uncontrolled or untreated CNS metastases and treated CNS metastases are allowed, aslong as the patient is clinically stable.
3. Presence carcinomatous meningeal involvement.
4. Patients may not be receiving any other investigational agents, or have participatedin any investigational drug study < 28 days prior to starting on the current study.
5. Since the teratogenic potential of AG01 is currently unknown, females who are pregnantor lactating are excluded.
6. Males and females unable to adhere to abstinence or use highly effective methods ofcontraception (annual failure rate < 1%) to prevent study subjects' pregnancy or studysubjects' partner pregnancy.
7. History of any other malignancies in the last 2 years except for in-situ cancer, basalor squamous cell skin cancer treated with curative intent.