NCT03519997

A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma

Active, enrolled Phase 2 Results posted Last updated 11 February 2026

What this trial tests

Phase 2 trial testing Pembrolizumab in Hepatocellular Carcinoma in 35 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

26 April 2018

Primary endpoint
21 April 2023

1 April 2026

Quick facts

Lead sponsor	David Hsieh
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	35
Start date	26 April 2018
Primary completion	21 April 2023
Estimated completion	1 April 2026
Sites	2 locations across United States

Drugs / interventions tested

• Pembrolizumab (pembrolizumab) — full drug profile →
• Bavituximab — full drug profile →

Conditions studied

• Hepatocellular Carcinoma — all drugs for Hepatocellular Carcinoma →

Sponsor

David Hsieh

Who can join

18 and older, any sex, with Hepatocellular Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate Primary · 36 months

To determine the overall response rate (ORR) defined as the number of complete or partial responses according to RECIST 1.1 divided by the number of evaluable patients treated with combination pembrolizumab and bavituximab in patients with advanced HCC.

Group	Value	95% CI
Pembro + Bavi	9

Number of Adverse Events According to the CTCAE Secondary · 36 months

To determine the safety and tolerability of combination pembrolizumab and bavituximab as measured by the number of adverse events according to the CTCAE 5.0

Group	Value	95% CI
Pembro + Bavi	33

Adverse events — posted to ClinicalTrials.gov

Time frame: The planned follow-up period was 36 months. However, due to patient deaths or lost to follow-up, not all patients had follow-up data for 36 months. The actual median follow-up time was 24 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembro + Bavi

Serious: 7/35 (20%)

Deaths: 14/35

Serious adverse events (11 terms)

Reaction	System	Pembro + Bavi
Hepatic failure	Hepatobiliary disorders	—
acute kidney insufficiency	Renal and urinary disorders	—
weakness	General disorders	—
sepsis	Infections and infestations	—
colitis	Gastrointestinal disorders	—
cough	Respiratory, thoracic and mediastinal disorders	—
fever	Infections and infestations	—
hypoglycemia	Endocrine disorders	—
hepatic hemorrhage	Hepatobiliary disorders	—
Renal calculi	Renal and urinary disorders	—
hyperglycemia	Endocrine disorders	—

Other adverse events (16 terms — click to expand)

Reaction	System	Pembro + Bavi
fatigue	General disorders	—
Diarrhea	Gastrointestinal disorders	—
rash	Skin and subcutaneous tissue disorders	—
AST increase	Hepatobiliary disorders	—
Neutrophil decrease	Blood and lymphatic system disorders	—
ALT increase	Hepatobiliary disorders	—
Chills	General disorders	—
anemia	Blood and lymphatic system disorders	—
constipation	Gastrointestinal disorders	—
dizziness	Nervous system disorders	—
vomiting	Gastrointestinal disorders	—
fever	General disorders	—
headache	Nervous system disorders	—
anorexia	Gastrointestinal disorders	—
hypoglycemia	Endocrine disorders	—
creatinine increase	Renal and urinary disorders	—

Most-reported serious reactions: Hepatic failure, acute kidney insufficiency, weakness, sepsis, colitis, cough, fever, hypoglycemia.

Data from ClinicalTrials.gov NCT03519997 adverse events section.

Sponsor's own description

This is a non-randomized, open-label, multi-site phase II therapeutic trial of pembrolizumab and bavituximab in patients with locally advanced HCC. Locally advanced or metastatic HCC is defined as disease that is not amenable to surgical and/or locoregional therapies. Subjects must not have received prior systemic therapy for advanced HCC in keeping with the first-line setting of this study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities.
   Lu C, Rong D, Zhang B, Zheng W, et al · · 2019 · cited 327× · PMID 31464625 · DOI 10.1186/s12943-019-1047-6
2. Advances in drug development for hepatocellular carcinoma: clinical trials and potential therapeutic targets.
   Luo XY, Wu KM, He XX. · · 2021 · cited 144× · PMID 34006331 · DOI 10.1186/s13046-021-01968-w
3. TIMs, TAMs, and PS- antibody targeting: implications for cancer immunotherapy.
   Dayoub AS, Brekken RA. · · 2020 · cited 39× · PMID 32087708 · DOI 10.1186/s12964-020-0521-5
4. Drug Treatment for Advanced Hepatocellular Carcinoma: First-Line and Beyond.
   Feng MY, Chan LL, Chan SL. · · 2022 · cited 37× · PMID 36005172 · DOI 10.3390/curroncol29080434
5. Cell Death in the Tumor Microenvironment: Implications for Cancer Immunotherapy.
   Gadiyar V, Lahey KC, Calianese D, Devoe C, et al · · 2020 · cited 37× · PMID 33003477 · DOI 10.3390/cells9102207
6. Immune Therapy for Liver Cancers.
   Hilmi M, Vienot A, Rousseau B, Neuzillet C. · · 2019 · cited 37× · PMID 31892230 · DOI 10.3390/cancers12010077
7. The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial.
   Hsiehchen D, Beg MS, Kainthla R, Lohrey J, et al · · 2024 · cited 31× · PMID 38467639 · DOI 10.1038/s41467-024-46542-y
8. Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies.
   Adams R, Osborn G, Mukhia B, Laddach R, et al · · 2022 · cited 22× · PMID 36211808 · DOI 10.1080/2162402x.2022.2127284