FDA Clears Phase 2 Trial of Leronlimab for Microsatellite-Stable CRC

• CytoDyn, the biotechnology company developing leronlimab, finalized the protocol of a phase 2 study evaluating the agent and gained regulatory clearance.
• The study is set to launch in partnership with Syneos Health, with a kickoff meeting planned for November 2024.
• Patient enrollment is expected to begin in early 2025.

The FDA has given clearance for the commencement of a phase 2 trial evaluating the efficacy of leronlimab for the treatment of patients with relapsed/refractory microsatellite stable colorectal cancer (CRC).¹

The phase 2 trial received clearance following productive feedback sessions with the FDA over recent months, culminating in the submission of the final study protocol in September 2024.

This trial, conducted in collaboration with Syneos Health, is set to kick off with a meeting in late November 2024, with patient enrollment slated to start in early 2025.

“We have appreciated the opportunity to work constructively with the FDA on the review and finalization of our CRC protocol,” said Jacob Lalezari, MD, chief executive officer, in a press release. “With the agency’s input and our partnership with Syneos Health, we are well positioned to advance our clinical evaluation of leronlimab for oncology and make real strides towards developing the treatment paths of tomorrow.”

Colorectal cancer image: © mi_viri - stock.adobe.com

In August 2024, the FDA met with CytoDyn to gain alignment on the rationale and proposed dosing for a phase 2 trial that will evaluate the investigational humanized Ig64 monoclonal antibody (mAb) leronlimab in combination with trifluridine plus tipiracil (Lonsurf; TAS-102) and bevacizumab (Avastin) in patients with CCR5+, microsatellite stable (MSS), relapsed/refractory metastatic colorectal cancer (mCRC), according to a news release.²

This combination is tailored for patients whose tumors express CCR5 and who have already undergone multiple lines of treatment, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, as well as anti-VEGF and anti-EGFR therapies when appropriate.

The phase 2, open-label, multicenter study will randomly assign approximately 60 patients with CCR5-positive MSS mCRC to receive either 350 mg or 700 mg of leronlimab. Patients will be divided into 2 cohorts, with an initial safety lead-in group receiving the 350 mg dose before advancing to the higher dose group. Leronlimab will be administered weekly, while TAS-102 and bevacizumab will be given on a 3- or 4-week schedule within a 4-week cycle.

Key eligibility criteria include measurable disease and prior exposure to standard mCRC therapies. CCR5 expression will be assessed through immunohistochemistry testing, and MSS status will be confirmed through IHC or next-generation sequencing.

Previous Data on Leronlimab in Oncology

Leronlimab has already shown potential in oncology, particularly in metastatic triple-negative breast cancer (mTNBC). A pooled analysis of 3 clinical trials presented at the 2022 American Society of Clinical Oncology Annual Meeting highlighted the possible benefits of leronlimab in mTNBC.³

Among 28 mTNBC patients treated with leronlimab at doses of 350 mg, 525 mg, or 700 mg, patients experienced a median progression-free survival (PFS) of 3.8 months and an overall survival (OS) of 6.6 months. In the subset of patients who received higher doses (525 mg or 700 mg), the median PFS extended to 6.1 months, with OS exceeding 12 months.

For safety, leronlimab was generally well tolerated, with few grade 3 treatment-emergent adverse events.

REFERENCES:

1. CytoDyn announces FDA clearance of its phase II oncology trial. News release. CytoDyn Inc. November 4, 2024. Accessed November 6, 2024. https://tinyurl.com/3ehctzy5

2. CytoDyn announces completion of FDA meeting on phase II study of leronlimab in patients with relapsed/refractory microsatellite stable colorectal cancer. News release. CytoDyn. August 12, 2024. Accessed November 6, 2024. https://tinyurl.com/3yc2am7s

3. Adams DL, Raghavakaimal A, Tang CM, et al. Safety, efficacy, and clinical outcomes of the anti-CCR5 inhibitor (leronlimab): a pooled analysis of three clinical trials in patients with mTNBC. J Clin Oncol. 2024;40(suppl 16). doi:10.1200/JCO.2022.40.16_suppl.e13062