FDA Fast Track Highlights Potential of Metabolic Reprogramming in HCC

The FDA has granted fast track designation to the anti-CD36 monoclonal antibody PLT012 for the treatment of patients with hepatocellular carcinoma (HCC).¹

The designation is intended to facilitate the development and expedite the review of new therapies for serious conditions with significant unmet medical needs. HCC remains one of the most common and lethal malignancies worldwide, frequently arising in the setting of chronic liver disease and cirrhosis. Despite recent therapeutic advances, many patients ultimately experience disease progression. Once frontline and subsequent options are exhausted, therapeutic choices become limited, underscoring the urgency of developing novel agents.

The fast track status provides opportunities to the sponsor for more frequent FDA interactions and eligibility for priority review or accelerated approval, potentially enabling the treatment to reach patients with HCC more quickly.

“Targeting CD36 represents a promising new way to reshape the tumor microenvironment [TME]. Importantly, we also start to reveal its superior activity on treating metabolic disorders,” said Ping-Chih Ho, co-founder of sponsor Pilatus Biosciences, in a news release.¹ “Importantly, PLT012 has the potential to redefine how we approach the [metabolic dysfunction-associated steatohepatitis (MASH)]-to-HCC continuum by intervening at the metabolic root of disease to treat and prevent progression.”

In addition to the new fast track designation, PLT012 also holds orphan drug designation from the FDA for the treatment of liver and intrahepatic bile duct cancer.²

PLT012: A Novel Approach to Metabolic Checkpoints

Unlike traditional immune checkpoint inhibitors that target the PD-1/PD-L1 or CTLA-4 pathways, PLT012 focuses on a "metabolic checkpoint" mediated by the fatty acid receptor CD36, which is known to promote HCC progression.³ High lipid levels within the TME are a hallmark of HCC, often leading to metabolic exhaustion in effector T cells and natural killer (NK) cells. CD36 facilitates the uptake of these lipids, ultimately inducing functional exhaustion in cytotoxic T cells.

PLT012 is a humanized IgG4 monoclonal antibody that selectively blocks CD36-mediated lipid uptake.^1,4 By interrupting this process, the agent aims to restore the metabolic fitness and effector functions of intratumoral CD8-positive T cells and NK cells. Simultaneously, the agent is intended to reduce the survival and suppressive activity of regulatory T cells and pro-tumor macrophages, both of which rely on CD36 for lipid-fueled metabolism in the TME.

This mechanism, previously explored in preclinical studies, positions the immunotherapy to “reprogram” antitumor immunity in HCC, thereby promoting stronger antitumor activity. In the preclinical models, PLT012 demonstrated robust preliminary antitumor activity as monotherapy and potential synergy with PD-1/PD-L1 inhibitors, supporting its continued development as both a single agent and as combination therapy.⁴

About the First-in-Human Study of PLT012

Following the FDA’s clearance of PLT012’s investigational new drug application in December 2025, a first-in-human phase 1 trial (NCT07337525) of the agent has been initiated. This open-label dose-escalation study is currently evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of PLT012 in adult patients with advanced solid tumors, including a dedicated cohort for HCC.⁵ Expansion cohorts are planned for specific tumor types.

Enrollment for the trial is ongoing at 2 sites in Texas for an estimated total of 36 patients. Patients with HCC must have Child-Pugh class A liver function and must not have had ascites requiring therapeutic paracentesis or hepatic encephalopathy requiring medical intervention within the past 6 months.

The investigation treatment regimen involves receiving PLT012 by intravenous infusion once every 3 weeks until disease progression or intolerable toxicity.

REFERENCES

1. Pilatus Biosciences receives FDA fast track designation for metabolic checkpoint inhibitor PLT012 in hepatocellular carcinoma. News release. Pilatus Biosciences. February 19, 2026. Accessed February 19, 2026. https://tinyurl.com/yptd496n

2. Pilatus Biosciences Inc. receives orphan drug designation from FDA for PLT012 in treatment of liver and intrahepatic bile duct cancer. News release. Pilatus Biosciences. November 1, 2024. Accessed February 19, 2026. https://tinyurl.com/y56wtkvw

3. Luo X, Zheng E, Wei L, et al. The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis. Cell Death Dis. 2021;12(4):328. Published 2021 Mar 26. doi:10.1038/s41419-021-03596-w

4. Tzeng SF, Yu YR, Park J, et al. PLT012, a humanized CD36-blocking antibody, is effective for unleashing antitumor immunity against liver cancer and liver metastasis. Cancer Disc. 2025;15(8):1676-1696. doi:10.1158/2159-8290.cd-24-1409

5. A first in human study of PLT012 in participants with solid tumor cancers. ClinicalTrials.gov. Updated February 18, 2026. Accessed February 19, 2026. https://clinicaltrials.gov/study/NCT07337525