ALG.APV-527 First-in-human Study

Inclusion Criteria:

• Have provided signed informed consent form (ICF) for participation in the study.
• Have a diagnosis of advanced solid tumor malignancy (histologically or cytologicallydocumented) that is metastatic or unresectable, have received standard of caretherapy, and remaining therapeutic options are participation in a clinical study ornon-curative therapy including best supportive care.
• Have one of the following tumors: non-small cell lung cancer (NSCLC),gastric/gastro-esophageal cancer, head and neck squamous cell carcinoma, renal cellcancer, ovarian cancer, breast cancer, malignant pleural mesothelioma, cervicalcancer, colorectal cancer, urothelial carcinoma, endometrial cancer, pancreaticcancer, or prostate cancer.
• Must be ≥ 18 years of age.
• ECOG performance status 0-1.
• Has provided tumor tissue biopsy material that has been obtained within 28 days priorto the first dose of study drug with ALG.APV-527. Biopsy material may be provided asFFPE block or as pre-cut slides of 7 to 10 sequential tissue sections.
• Should have recovered from AEs due to prior anticancer medications to at least ≤Grade 1 by CTCAE version 5.0, except for alopecia, vitiligo, resolved atopy, and white bloodcell count (see inclusion criterion #13).
• Must have at least 1 measurable lesion by computed tomography (CT) or magneticresonance imaging (MRI) per RECIST Version 1.1.
• Must have a life expectancy of ≥3 months.
• For women of childbearing potential and men with partners of childbearing potential,agreement to use a highly effective method of birth control for the duration of studytreatment and for at least 9 months after the last dose of study treatment:
• Combined (estrogen and progesterone containing) hormonal contraception associatedwith inhibition of ovulation (oral, intravaginal, or transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence (defined as refraining from heterosexual intercourse during theentire study and for 9 months after the last dose of study treatment and must bethe preferred and usual lifestyle of the patient)
• Females of childbearing potential must have a negative serum or urine pregnancy test.
• Must have adequate coagulation function at Screening as determined by:
• PT international normalized ratio (INR) ≤ 1.5.

≤ 1.5 × ULN. Patients on full dose of oral anticoagulation must be on thisdose for a minimum duration of 14 days before the first dose of study drug; ifreceiving warfarin, the patient must have an INR ≤ 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study drug); patients onlow molecular weight heparin will be allowed.

• Must have adequate hematologic function at Screening as determined by:
• White blood count cell (WBC) ≥ 2000/µL.
• Absolute neutrophil count (ANC) ≥ 1500/µL (patient may not use G-CSF or GMCSF toachieve these WBC and ANC levels).
• Platelet count ≥ 100 × 103/µL.
• Hemoglobin (Hgb) ≥ 9.0 g/dL (may not transfuse or use erythropoietin to obtainthis Hgb level; transfusions are allowed up to 2 weeks prior to C1D1).
• Must have adequate renal and hepatic function at Screening as determined by:
• Adequate renal function (estimated glomerular filtration rate [eGFR] > 40 mL/minaccording to the Cockcroft-Gault formula).
• Total bilirubin ≤ 1.5 × ULN (or ≤ 3.0 × ULN for patients with liver metastases orknown Gilbert's syndrome).
• AST and ALT ≤ 2.5 × ULN (≤ 5.0 × ULN in patients with documented livermetastasis).
• Alkaline phosphatase ≤ 2.5 x ULN (≤ 5.0 × ULN in patients with documented liveror bone metastases)
• Must be able to attend study visits as required by the protocol.

Exclusion Criteria:

• Has received anti-cancer chemotherapy (including molecular-targeted drugs),radiotherapy (therapeutic or curative intent) or hormonal therapy within 14 daysbefore the first dose of ALG.APV-527; however, the following are permitted:
• Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists orantagonists for prostate cancer
• Hormone-replacement therapy or oral contraceptives
• Herbal therapy intended as anti-cancer ≥ 1 week prior to first dose ofALG.APV-527
• Palliative radiotherapy for bone metastases within 2 weeks prior to first dose ofALG.APV-527
• Has received immunotherapy (e.g., CAR T-cell therapy, T-cell redirecting bispecificantibodies, mono-specific antibodies, vaccines or cytokines), or investigationalagents within 28 days before the first dose of ALG.APV-527.
• Receives concurrent systemic (oral or IV) steroid therapy >10 mg methylprednisolonedaily or its equivalent for an underlying, non-cancer condition. Concurrentcorticosteroid therapy as anticancer drug (any dose) is considered exclusionary.
• Has had major surgery within the 4 weeks before the first dose of ALG.APV-527.
• History of, or known, central nervous system (CNS) disease involvement (e.g.,glioblastoma [GBM]), carcinomatous meningitis, CNS metastases including spinalmetastases with a risk of spinal cord compression (spinal metastases not associatedwith a risk of spinal cord compression are acceptable); CNS metastases that aretreated and not progressing are acceptable.
• Has seizures requiring anticonvulsant treatment or has a history of a cerebrovascularaccident or transient ischemic attack less than 6 months ago.
• Has uncontrolled or severe intercurrent medical condition or a significant history ofrenal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic,cardiovascular, or hepatic disease that in the opinion of the investigator wouldadversely affect the patient's participation in this trial.
• Has interstitial lung disease or active, non-infectious pneumonitis.
• Has a history of autoimmune disease active or past including but not limited toinflammatory bowel disease, systemic lupus erythematosus (SLE), ankylosingspondylitis, scleroderma, or multiple sclerosis. Has any active immunologic disorderrequiring immunosuppression with steroids >10mg methylprednisolone daily or itsequivalent or other immunosuppressive agents (e.g., azathioprine, cyclosporine A) withthe exception of patients with isolated vitiligo, resolved childhood asthma or atopicdermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid patients witha history of Grave's disease. Patients with controlled hyperthyroidism must benegative for thyroglobulin, thyroid peroxidase antibodies, and thyroid-stimulatingimmunoglobulin prior to study drug administration.
• Has a known hypersensitivity to a component of the protocol therapy, ALG.APV-527.
• Has a history of another primary cancer within the 5 years prior to enrollment exceptfor the following: non-melanoma skin cancer, cervical carcinoma in situ, superficialbladder cancer, or other non-metastatic carcinoma that has been in complete remissionwithout treatment for more than 5 years.
• Has abnormal electrocardiograms (ECGs) that are clinically significant, such as QTprolongation (corrected QT interval [QTcF] > 470 msec).
• In the opinion of the treating Investigator, has any concurrent conditions that couldpose an undue medical hazard or interfere with the interpretation of the studyresults; these conditions include, but are not limited to ongoing or active infection,clinically significant non-healing or healing wounds, concurrent congestive heartfailure (New York Heart Association Functional Classification Class II, III or IV),concurrent unstable angina, concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation), recent (within the prior 12 months)myocardial infarction, acute coronary syndrome or stroke within the previous 12months, significant valvular disease, cardiomegaly, ventricular hypertrophy, orcardiomyopathy, significant pulmonary disease (shortness of breath at rest or on mildexertion), for example, because of concurrent severe obstructive pulmonary disease,concurrent hypertension requiring more than 2 medications for adequate control, ordiabetes mellitus with more than 2 episodes of ketoacidosis in the prior 12 months.
• Has an ejection fraction (EF) of 50% or less based on a multi-gated acquisition (MUGA)scan or echocardiogram (ECHO).
• Patient has any active, uncontrolled, or suspected infection at the time of signingICF or within 3 days prior to treatment start.
• Has the presence of a known active acute or chronic infection (viral, bacterial,systemic fungal) including human immunodeficiency virus (HIV) as determined byenzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot; and hepatitisB virus (HBV) and hepatitis C virus (HCV) as determined by hepatitis B surface antigen (HBsAg) and hepatitis C serology (prophylactic therapy according to institutionalprotocols is acceptable).
• Has a cognitive, psychological, or psychosocial impediment that would impair theability of the patient to receive therapy according to the protocol or adverselyaffect the ability of the patient to comply with the informed consent process,protocol, or protocol-required visits and procedures.
• Pregnant or breastfeeding.
• Have been exposed to live attenuated vaccine within 4 weeks prior to first dose ofALG.APV-527.
• Participation or plans to participate in another interventional clinical study whiletaking part in this protocol; participation in an observational study is acceptable.