PLT012 Receives IND Clearance from FDA for Solid Tumors

The US FDA has cleared the investigational new drug application for PLT012, a first-in-class anti-CD36 monoclonal antibody, to enter clinical development for the treatment of patients with solid tumors.¹

Pilatus Biosciences Inc, the developer of PLT012, plans to initiate a phase 1 clinical trial in the first quarter of 2026.

PLT012 is a metabolic checkpoint antibody designed to block CD36-mediated lipid uptake and immune suppression within the tumor microenvironment (TME). PLT012 is engineered to restore metabolic fitness in cytotoxic T cells, reduce immunosuppressive cell populations, and promote stronger antitumor immune responses. PLT012 has been promising in the preclinical setting, demonstrating monotherapy activity across immune-hot and immune-cold tumors while also showing potential synergy with PD-1/PD-L1 inhibitors.

“Targeting CD36 represents a promising new way to reshape the [TME],” said Anthony El-Khoueiry, MD, lead principal investigator of the trial, in a news release. “PLT012’s ability to modulate metabolic dysfunction and reinvigorate exhausted T cells positions it as a potentially important therapeutic option for tumors that do not respond to current immunotherapies.”

The upcoming phase 1 trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary signs of clinical activity, with expansion cohorts planned for tumor types strongly influenced by CD36-mediated metabolic dysregulation.

In December 2024, PLT012 received FDA orphan drug designation for the treatment of patients with live and intrahepatic bile duct cancers.²

“The hepatic microenvironment is tolerogenic and macrophage-rich which can dampen effector T-cell activity, contributing to weaker responses to immunotherapy treatments for [hepatocellular carcinoma] HCC and liver metastases,” said Anthony W. Tolcher, MD, of New Experimental Therapeutics in San Antonio, Texas, in a news release.¹ “Preclinical data has shown that PLT012 can overcome this immunogenically cold environment and elicit strong anticancer effects, which we hope will be translated into improved patient outcomes in the planned [p]hase 1 clinical trial.”

PLT012 in a Clinical Setting

In a study investigating PLT012, the agent demonstrated its capacity to block CD36-mediated metabolic changes in both regulatory T cells (Tregs) and CD8+ tumor-infiltrating lymphocytes.³

To assess its effectiveness, investigators used a concurrent MC38 liver metastasis murine model. The mechanism of action was further validated using human liver metastasis samples within an ex vivo culture platform.

In an in-silico analysis of 1 patient cohort, researchers examined the mechanism of PLT012 and found that liver metastases—regardless of the primary tumor—share TME features with HCC. These shared features include elevated fatty acid signatures, increased Treg percentages, and decreased CD8+ cell infiltration.

Administration of PLT012 in the MC38 syngeneic mouse model with liver metastasis resulted in a significant reduction in tumor growth in both the liver metastases and subcutaneous tumors. This reduction was accompanied by favorable TME changes: a decreased M2 macrophage population, a reduced Treg population, and an increased CD8+ T cell population. These findings were consistent with ex vivo observations of PLT012 activity in human liver metastatic samples.

The investigators further highlighted that PLT012 mitigated liver metastasis-dependent resistance to immune checkpoint inhibitors, effectively resensitizing subcutaneous tumors to anti-PD1 treatment. These results support the potential utility of immunometabolic targeting as a strategy in cancer immunotherapy.

REFERENCES

1.Pilatus Biosciences announces FDA clearance of IND application for PLT012, a first-in-class anti-CD36 metabolic checkpoint antibody in solid tumors. News release. Pilatus Biosciences. December 15, 2025. Accessed December 16, 2025. https://tinyurl.com/4pushced

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 December 16, 2025. https://tinyurl.com/mssf665m

3.Yu YR, Tzeng SF, Hsiao HW, Lin YH, Tsai CH, Ho PC. 1346 PLT012: a first-in-class antibody targeting CD36, revolutionizing immunotherapy by unleashing anti-tumor immunity through metabolic reprogramming in the tumor microenvironment. JITC. 12(Suppl 2):A1503-A1503. doi:10.1136/jitc-2024-SITC2024.1346