Study of SRF231 in Patients With Advanced Solid and Hematologic Cancers
Study of SRF231 in Patients With Advanced Solid and Hematologic Cancers
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.