This Phase 1/1b, open-label, first-in-human, monotherapy study will be conducted in 2 parts. Part A will consist of the SRF231 monotherapy dose-escalation portion of the study, and will enroll up to 48 patients with advanced solid tumors and hematological cancers. Part B will include monotherapy expansion cohorts in advanced solid and hematologic cancers to further examine SRF231 as monotherapy (100 patients total).

This first-in-human study is designed to evaluate the safety and tolerability of SRF231 as a monotherapy via dose escalation (Part A), and to determine the dose(s) of SRF231 to be further examined in expansion cohorts as monotherapy. The preliminary clinical activity of SRF231 administered as monotherapy will be characterized, along with pharmacokinetics (PK) and pharmacodynamics. In Part B, the safety and tolerability of SRF231 as monotherapy will be evaluated in select patient cohorts of advanced cancers and evaluate clinical activity. The study also is designed to examine the effect of SRF231 monotherapy on peripheral blood immune cell subsets, peripheral blood gene expression, and serum biomarkers

Inclusion Criteria:

1. ≥18 years of age.

2. Failure to respond to standard therapy, and for whom no appropriate therapies are available (based on the judgment of the Investigator).

3. Histological or cytological evidence of advanced, relapsed, or refractory, solid and hematologic cancers that are not a candidate for curative therapy.

4. Part B only: Patient must have demonstrated progressive disease (PD) after the most recent treatment regimen (or within 3 months prior to enrollment in the case of treatment-naïve patients).

5. Washout period from the last dose of previous anticancer therapy (chemotherapy, biologic, or other investigational agent) to the initiation of study drug must be > 5 times the half-life of the agent or > 21 days (whichever is shorter).

   Note: the washout period for palliative radiotherapy is 7 days.

6. Resolution of adverse events (AEs) related to prior anticancer therapy (including immune-related AEs but excluding alopecia) to ≤ Grade 1 per NCI-CTCAE v. 4.03 or higher.

7. Measurable disease per applicable disease-specific criteria for Part B only.

8. Serum creatinine clearance ≥ 60 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN).

9. Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated due to Gilbert's syndrome).

10. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < 2.5 x ULN ( < 5 x ULN if liver metastasis).

11. Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L.

12. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

13. Ejection fraction ≥ 50%, as measured by echocardiogram or multigated acquisition (MUGA) scan at Screening.

14. For women of childbearing potential (WCBP): negative serum beta human chorionic gonadotropin (betahCG) pregnancy test within 1 week before first treatment (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally postmenopausal for at least 12 consecutive months for women > 55 years of age).

15. Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study treatment, including 30 days after the last dose of SRF231. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception. Azoospermic males and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However female patients must still undergo pregnancy testing as described in this section.

16. Ability to adhere to the study visit schedule and all protocol requirements.

17. Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form before any screening procedures are performed.

Exclusion Criteria:

1. Previously received an anti-CD47 antibody or SIRPalpha targeted therapy.
2. High-grade lymphomas (eg, Burkitt's, lymphoblastic), plasma cell leukemia.
3. History of any condition known to be associated with reduced red blood cell (RBC) lifespan (eg, thalassemia trait, glucose-6-phosphate dehydrogenase deficiency).
4. History of ≥ Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or any excipient in the study drugs.
5. Major surgery within 4 weeks prior to Screening.
6. Symptomatic or untreated brain metastases (including leptomeningeal metastases).
7. Primary central nervous system malignancy.
8. Part A only: Prior RBC or platelet transfusion < 4 weeks prior to starting SRF231.
9. Prior autologous stem cell transplant ≤ 3 months prior to starting SRF231.
10. Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus.
11. Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids at doses used as anticancer therapy (ie, > 20 mg/day prednisone or equivalent) Note: topical, intranasal, or inhaled corticosteroids and physiologic replacement for patients with adrenal insufficiency are allowed.
12. Ongoing uncontrolled systemic bacterial, fungal, or viral infections at Screening Note: oral antibiotics for a controlled infection are permitted. Patients on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met.
13. Administration of a live vaccine within 6 weeks of first dose of study drug.
14. Prior allogeneic hematopoietic cell transplant within 6 months or with clinical Graft-Versus-Host Disease.
15. Previous chimeric antigen receptor (CAR)-T/T-cell receptor (TCR) cellular therapy with detectable circulating CAR-T/TCR cells.
16. History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, atypical hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura.
17. Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms. Note: criterion does not apply to patients with a right or left bundle branch block.
18. Female patients who are pregnant or breastfeeding.
19. Concurrent active malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix.
20. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening.
21. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study.