Study of SRF231 in Patients With Advanced Solid and Hematologic Cancers

NCT03512340 | Completed Phase 1 FDA Drug

• 1 other identifier: SRF231-101
• Study Type: interventional
• Target: 148
• Locations: 2 countries
• Sites: 3

Brief Summary

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).

Conditions

Advanced Solid Cancers; Hematologic Cancers

Keywords

CD47; SiRP α; tumor microenvironment; macrophage; solid tumor; Phase 1; safety; efficacy; hematologic malignancies; SRF231

Outcome Measures

Primary Outcomes (4)

• [Part A] Dose-limiting toxicity (DLT)

  The number of patients in Part A who experienced a DLT during Cycle 1 or completed at least 75% of the prescribed Cycle 1 SRF231 dose will be used to assess tolerability and determine the appropriate dose for Part B.

  Through 24 months with 21 day drug treatment cycles

• [Part A] Non-tolerated Dose (NTD)

  For Part A, the NTD is the dose level at which 2 or more patients experience a DLT in the first cycle of treatment.

  Through 24 months with 21 day drug treatment cycles

• [Part A] Maximum tolerated Dose (MTD)

  For Part A, the MTD is defined as the dose level immediately below the non-tolerated dose (NTD). A total of 6 patients must be treated at a dose level for it to be considered the MTD.

  Through 24 months with 21 day drug treatment cycles

• [Parts A and B] Safety Analysis: summarizing adverse events (AEs) and will be based on treatment-emergent AEs (TEAEs)

  Safety and tolerability of SRF231 monotherapy will be assessed by summarizing adverse events (AEs) and will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE that emerges or worsens in the period from the first dose of study treatment to 30 days after the last dose of study drug assessed by per CTCAE version 4.03 or higher.

  Through 24 months with 21 day drug treatment cycles

Secondary Outcomes (11)

• [Parts A and B] Maximum serum concentration (Cmax) of SRF231

  Up to 24 months

• [Parts A and B] Time to maximum serum concentration (tmax) of SRF231

  Up to 24 months

• [Parts A and B] Area under the serum concentration-time curve from time zero to the last quantifiable time point (AUC 0-last) of SRF231

  Up to 24 months

• [Parts A and B] Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC 0-INF) of SRF231

  Up to 24 months

• [Parts A and B] Terminal elimination half-life (t1/2) of SRF231

  Up to 24 months

Study Arms (2)

Part A

EXPERIMENTAL

Part A will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of SRF231 as a monotherapy in patients with advanced solid tumors and lymphoma/Chronic lymphocytic leukemia.

Drug: SRF231

Part B Cohort 1

EXPERIMENTAL

Depending upon the results from Part A of the study and the decision from the Safety Review Committee, 1 or 2 doses or dosing frequencies of SRF231 in select advanced solid and hematologic malignancies.

Drug: SRF231

Interventions

SRF231 DRUG

SRF231 specifically blocks the interaction between CD47 and signal regulatory protein alpha and acts as a potent enhancer of human tumor cell phagocytosis.

Part A; Part B Cohort 1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age.
• Failure to respond to standard therapy, and for whom no appropriate therapies are available (based on the judgment of the Investigator).
• Histological or cytological evidence of advanced, relapsed, or refractory, solid and hematologic cancers that are not a candidate for curative therapy.
• 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).
• 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.
• 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.
• Measurable disease per applicable disease-specific criteria for Part B only.
• Serum creatinine clearance ≥ 60 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated due to Gilbert's syndrome).
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \< 2.5 x ULN ( \< 5 x ULN if liver metastasis).
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Ejection fraction ≥ 50%, as measured by echocardiogram or multigated acquisition (MUGA) scan at Screening.
• 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).

You may not qualify if:

• Previously received an anti-CD47 antibody or SIRPalpha targeted therapy.
• High-grade lymphomas (eg, Burkitt's, lymphoblastic), plasma cell leukemia.
• History of any condition known to be associated with reduced red blood cell (RBC) lifespan (eg, thalassemia trait, glucose-6-phosphate dehydrogenase deficiency).
• History of ≥ Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or any excipient in the study drugs.
• Major surgery within 4 weeks prior to Screening.
• Symptomatic or untreated brain metastases (including leptomeningeal metastases).
• Primary central nervous system malignancy.
• Part A only: Prior RBC or platelet transfusion \< 4 weeks prior to starting SRF231.
• Prior autologous stem cell transplant ≤ 3 months prior to starting SRF231.
• Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus.
• 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.
• Administration of a live vaccine within 6 weeks of first dose of study drug.
• Prior allogeneic hematopoietic cell transplant within 6 months or with clinical Graft-Versus-Host Disease.
• Previous chimeric antigen receptor (CAR)-T/T-cell receptor (TCR) cellular therapy with detectable circulating CAR-T/TCR cells.
• History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, atypical hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura.

Sponsors & Collaborators

• Surface Oncology: lead

Study Sites (3)

Research Site 002

New York, New York, 10065, United States

Location

Research Site 001

San Antonio, Texas, 78229, United States

Location

Research Site 101

Toronto, Ontario, M5G1Z5, Canada

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Robert Ross, MD

  Surface Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 lymphoma/CLL. Part B will include 5 monotherapy expansion cohorts: in advance solid and hematologic cancers (100 patients total).

Study Record Dates

• First Submitted: March 13, 2018
• First Posted: April 30, 2018
• Study Start: March 13, 2018
• Primary Completion: September 15, 2020
• Study Completion: September 29, 2020
• Last Updated: October 20, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); CA (1)