BO-112 and Pembrolizumab for the Treatment of PD-1/PD-L1 Refractory Liver Cancer

NCT04777708 | Terminated Early Phase 1 DMC FDA Drug

• 2 other identifiers: 21-000276NCI-2021-00994
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase I trial evaluates the side effects of BO-112 and pembrolizumab and how well they work in treating patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C liver cancer. Immunotherapy with BO-112, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving BO-112 and pembrolizumab may help treat patients with liver cancer.

Conditions

Advanced Hepatocellular Carcinoma; BCLC Stage B Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma; Refractory Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR will be estimated and 95% Clopper-Pearson exact confidence intervals (CIs) will be provided.

  Up to 4 years

Secondary Outcomes (5)

• Progression-free survival (PFS)

  From Cycle 1 day 1 (each cycle is 21 days) to the first documented disease progression or death due to any cause, whichever occurs first, assessed up to 4 years]

• Time to progression (TTP)

  From Cycle 1 day 1 (each cycle is 21 days) to the first documented disease progression, assessed up to 4 years]

• Disease control rate (DCR)

  Up to 4 years

• Overall survival (OS)

  From Cycle 1 day 1 (each cycle is 21 days) to death due to any cause, assessed up to 4 years]

• Incidence of adverse events

  Up to 4 years

Study Arms (1)

Treatment (pembrolizumab, BO-112)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 of odd number cycles. Patients also receive BO-112 by intratumoral injection on day 1, 8, and 15 of cycle 1, and day 15 of subsequent cycles. Treatment repeats every 3 weeks for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Nanoplexed Poly I:C BO-112; Biological: Pembrolizumab

Interventions

Nanoplexed Poly I:C BO-112 BIOLOGICAL

Given by intratumoral injection

Also known as: BO 112, BO-112, BO112, Nanoplexed Poly IC BO-112, Nanoplexed Polyinosinic:Polycytidylic Acid BO-112

Treatment (pembrolizumab, BO-112)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, BO-112)

Eligibility Criteria

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

You may qualify if:

• Participants who are at least 18 years of age on the day of signing informed consent with confirmed diagnosis of hepatocellular carcinoma by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) will be enrolled in this study.
• Radiologic confirmation diagnosis is provided by the study site. Clinically confirmed diagnosis of HCC as per the American Association for the Study of Liver Diseases (AASLD) criteria, which requires:
• Radiographically evident cirrhosis AND
• A liver mass that shows arterial phase hyperenhancement on triphasic computed tomography (CT) or magnetic resonance imaging (MRI), AND EITHER:
• Is \>= 20 mm with either non-peripheral portal washout or an enhancing capsule OR
• Is 10-19 mm with non-peripheral portal venous washout AND an enhancing capsule
• Have Barcelona Clinic Liver Cancer (BCLC) stage C disease, or BCLC stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
• Have a Child-Pugh class A liver score within 14 days of first dose of study drug
• Have a predicted life expectancy of \> 3 months
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days/weeks (corresponding to time needed to eliminate any study treatment(s) after the last dose of study treatment.
• Note: a male participant is not required to use contraception during the treatment period for pembrolizumab and BO-112. BO-112 does not have any evidence of genotoxicity at any dose
• Participants must have progressed radiographically on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other adjunct therapies. Participants must not have received BO-112 previously. PD-1/L1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to C1D1. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to C1D1. Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to=\< grade 1 or baseline. Participants with =\< grade 2 neuropathy may be eligible. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• Has had esophageal or gastric variceal bleeding within the last 6 months
• Has clinically apparent ascites on physical examination
• Note: ascites detectable on imaging studies only are allowed
• Has had clinically diagnosed hepatic encephalopathy in the last 3 months. Subjects on rifaximin or lactulose to control their hepatic encephalopathy are not allowed
• Has received locoregional therapy to liver (transcatheter chemoembolization \[TACE\], transcatheter embolization \[TAE\], hepatic arterial infusion \[HAI\], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study drug. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-liver, non-central nervous system (CNS) disease
• Prior treatment with any Toll-like receptor (TLR) agonist
• Has liver lesions with macroscopic tumor infiltration into the main portal vein, hepatic vein, or inferior vena cava
• Has had major surgery to liver or other site within 4 weeks prior to the first dose of study drug
• Has had a minor surgery (i.e., simple excision, tooth extraction) =\< 7 days prior to the first dose of study treatment (cycle 1, day 1)
• Contraindications to tumor biopsy and injections of the hepatic metastasis(es), such as coagulopathy, therapeutic dose anticoagulant treatment and/or treatment with long-acting agents such as clopidogrel which cannot be safely stopped
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Highlight Therapeutics: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

BO-112; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Richard S Finn

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 2, 2021
• Study Start: October 13, 2021
• Primary Completion: March 13, 2023
• Study Completion: March 13, 2023
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

US (1)