Phase 1 Study of SF1126 in Combination With Nivolumab in Patients With Advanced Hepatocellular Carcinoma

NCT03059147 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 161007FD-05113
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives:

1. 1.To determine the maximum tolerated dose (MTD) or maximum recommended dose of SF1126 in combination with nivolumab in adult patients with advanced (unresectable or metastatic) HCC and Child-Pugh A or Child-Pugh B7 cirrhosis.
2. 2.To determine the recommended phase II dose of SF1126 in combination with nivolumab in patients with advanced (unresectable or metastatic) HCC and Child-Pugh A or Child-Pugh B7 cirrhosis.
3. 3.To describe the safety and tolerability of SF1126 in adult patients with underlying liver disease by ongoing evaluation of adverse events.
4. 4.To determine pharmacokinetics in HCC patients.
5. 5.To assess the effect of SF1126 in combination with nivolumab on progression-free survival and overall survival.
6. 6.Adverse events related to SF1126 (description, timing, grade \[CTCAE v4.03\], severity, seriousness, and relatedness).
7. 7.Pharmacokinetics in HCC patients.
8. 8.The proportion of patients remaining progression-free by radiographic criteria as assessed by RESIST v1.1 at 4 months, and, as available, median progression-free survival and overall survival estimated using the Kaplan-Meier method.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of dose limiting toxicities

  A dose limiting toxicity is a clinically significant adverse event (AE) occurring within 56 days of investigational treatment that is considered by the investigator to be possibly, probably, or definitely related to SF1126

  Occurring within 56 days of investigational treatment

Secondary Outcomes (4)

• Treatment-emergent adverse events

  3 years

• Peak plasma concentration (Cmax)

  3 years

• Area under the plasma concentration versus time curve (AUC)

  3 years

• Progression-free survival

  4 months

Study Arms (1)

SF1126 + Nivolumab

EXPERIMENTAL

SF1126 900-1100 mg/m2 IV twice weekly + Nivolumab 240 mg IV every 2 weeks

Drug: SF1126; Drug: Nivolumab

Interventions

SF1126 DRUG

SF1126 is a dual PI3 kinase/BRD4 inhibitor small molecule. It will be administered IV twice weekly (900 mg/m2 starting dose with escalation to 1000 mg/m2 per dose and 1100 mg/m2 per dose) at a dose determined by the cohort the patient is enrolled in until progression or unacceptable toxicity develops.

SF1126 + Nivolumab

Nivolumab DRUG

Nivolumab is a humanized, IgG4 isotype monoclonal antibody that binds to PD-1 and blocks binding of PD-1 to its ligands PD-L1 and PD-L2. It will be administered at 240 mg IV every 2 weeks until progression or unacceptable toxicity develops.

SF1126 + Nivolumab

Eligibility Criteria

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

You may qualify if:

• To qualify for enrollment, all of the following criteria must be met:
• Willing and able to provide written informed consent prior to performance of any study-specific procedures.
• Age ≥ 18 years.
• Histological or radiologic diagnosis of advanced (unresectable or metastatic) HCC with Child-Pugh A or Child-Pugh B7 cirrhosis:
• The diagnosis of HCC will be made according to the European Association for the Study of the Liver-European Organization for Research and Treatment of Cancer Clinical Practice Guidelines (EASL EASL-EORTC CPG) and according to successive modifications of the American Association for the Study of Liver Disease (AASLD) practice guidelines.
• Pathological diagnoses of HCC will be made according to the International Working Party criteria.
• Is not a candidate for local therapies, including liver transplantation, tumor ablation, transarterial embolization, or resection.
• No known FDA-approved therapy available that is expected to prolong survival by greater than 3 months.
• ECOG Performance Status ≤ 2.
• Has measurable or evaluable disease as per RECIST v1.1.
• Life expectancy of ≥ 12 weeks.
• Has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy:
• Myelosuppressive chemotherapy: At least 3 weeks since completion (6 weeks for nitrosourea)
• Biologic (anti-neoplastic agent): At least 7 days since completion of therapy with a biologic agent.
• Radiation (XRT): ≥ 1 week must have elapsed from prior palliative XRT to non-target lesions.

You may not qualify if:

• Brain metastases or spinal cord compression, unless treatment was completed at least 4 weeks before study entry, and stable without steroid treatment for at least 4 weeks.
• Evidence of severe or uncontrolled systemic diseases \[e.g., unstable or uncompensated respiratory, cardiac (including life threatening arrhythmias)\].
• Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor.
• Presence of cardiac impairment defined as:
• QTc prolongation defined as QTc ≥ 480 ms by ECGs; OR
• prior history of cardiovascular disease including heart failure that meets New York Hearth Association (NYHA) class III and IV definitions; OR
• history of myocardial infarction/active ischemic heart disease within one year of study entry; OR
• uncontrolled dysrhythmias; OR
• poorly controlled angina.
• Participation in a trial of an investigational agent within the prior 30 days.
• Pregnant or breast-feeding females.
• High volume peritoneal or pleural effusions requiring a tap more frequently than every 14 days. Moderate to severe ascites.
• Poorly controlled or refractory (grade 3-4) hepatic encephalopathy.
• History of other malignancies except curatively excised carcinoma in situ of the cervix, non-melanoma skin cancer or superficial bladder cancer or other solid tumors curatively treated with no evidence of disease for ≥ 5 years. Other cases will be reviewed and possibly allowed if discussed with and approved by Medical Monitor.
• Patients receiving therapeutic doses of warfarin. Lovenox is permitted.

Sponsors & Collaborators

• SignalRX Pharmaceuticals, Inc.: lead
• University of California, San Diego: collaborator

Study Sites (1)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Related Publications (1)

• Lucibello G, Mograbi B, Milano G, Hofman P, Brest P. PD-L1 regulation revisited: impact on immunotherapeutic strategies. Trends Mol Med. 2021 Sep;27(9):868-881. doi: 10.1016/j.molmed.2021.06.005. Epub 2021 Jun 26.

  PMID: 34187739 DERIVED

Related Links

• SignalRx Pharmaceuticals website

MeSH Terms

Interventions

SF 1126; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3 + 3 Designed Phase I study

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 23, 2017
• Study Start: March 27, 2017
• Primary Completion: April 22, 2019
• Study Completion: June 29, 2020
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)