Leronlimab Shows Early Clinical and Biomarker Activity in Metastatic Colorectal Cancer at AACR 2026

CytoDyn Inc. reported new clinical and translational data from its ongoing Phase 2 study of leronlimab in metastatic colorectal cancer (mCRC), presented at the American Association for Cancer Research Annual Meeting 2026,¹ highlighting early signals of activity when combined with standard-of-care therapy.

The data evaluate leronlimab—a humanized monoclonal antibody targeting the CCR5 receptor—in combination with TAS-102 and bevacizumab in previously treated patients with mCRC, a population with limited treatment options following progression on multiple prior lines of therapy. The study is assessing whether targeting the CCR5 receptor can help reshape the tumor microenvironment and enhance immune-mediated anti-tumor response.

Leronlimab is implicated in immune modulation and tumor biology. According to investigators, CCR5 inhibition may improve responsiveness to chemotherapy by reducing immune suppression within the tumor microenvironment.

Early Biomarker and Clinical Signals

Among pre-screened patients with evaluable samples (n=33), CCR5 expression was detected in 100% of cases, supporting its potential relevance as a therapeutic target in mCRC. Early biomarker activity was observed, including rapid reductions in circulating tumor DNA (ctDNA), with median declines of approximately 70% by week 2 in evaluable patients (n=19).

Investigators also reported that the combination regimen was generally well-tolerated, with no dose-limiting toxicities attributed to leronlimab. Dose escalation to 700 mg is currently underway as the study continues to enroll patients.

“These preliminary results suggest CCR5 inhibition with leronlimab may enhance both biomarker and clinical responses in heavily pretreated mCRC patients,” said Pashtoon M. Kasi, MD, MS, in a press release.² He noted that emerging liquid biopsy approaches, including ctDNA and circulating tumor cell analysis, are providing earlier insights into treatment response than conventional imaging alone.

Mechanistic Rationale and Tumor Microenvironment Effects

In patients who have exhausted standard therapies, mCRC remains particularly difficult to treat. Current regimens such as TAS-102 plus bevacizumab offer modest benefit, but durable responses remain limited due to treatment resistance and immune evasion.

Researchers suggest that CCR5 plays a role in shaping immune cell infiltration and tumor-associated macrophage activity. By inhibiting this pathway, leronlimab may enhance immune engagement and improve the effectiveness of existing chemotherapy backbones.

Ongoing Development and Expansion

The Phase 2 study continues to enroll patients toward full accrual, reflecting persistent unmet need in refractory mCRC. The program builds on earlier translational and clinical findings in other solid tumors, including metastatic triple-negative breast cancer, where similar immune-modulating effects have been observed.

“These early signals further support CCR5 as a key regulator of the tumor microenvironment across multiple tumor types,” said Jacob P. Lalezari, MD, chief executive officer of CytoDyn. He added that combination strategies involving leronlimab may offer a potential approach to overcoming resistance in heavily pretreated populations.

The poster, titled “Preliminary results of a Phase 2 study of leronlimab in combination with TAS-102 and bevacizumab in previously treated metastatic colorectal cancer,” was presented during AACR 2026 in San Diego.

Collectively, the findings add to a growing body of early-stage evidence exploring CCR5 inhibition as a potential immunomodulatory strategy in solid tumors.

References

1. Kasi, PM, Baron, A, Chaudhry, A, Tenner, L. (April 2026). Abstract 6466: Preliminary results of a phase 2 study of leronlimab in combination with TAS-102 and bevacizumab in previously treated metastatic colorectal cancer. ResearchGate.

https://www.researchgate.net/publication/403493585_Abstract_6466_Preliminary_results_of_a_phase_2_study_of_leronlimab_in_combination_with_TAS-102_and_bevacizumab_in_previously_treated_metastatic_colorectal_cancer

2. CytoDyn Presents New Leronlimab Data in Metastatic Colorectal Cancer at AACR Annual Meeting 2026. (2026 Apr 22). CytoDyn. https://www.cytodyn.com/newsroom/detail/661/cytodyn-presents-new-leronlimab-data-in-metastatic