FDA Holds Meeting for Leronlimab Rationale, Dosing in CCR5+ MSS mCRC

CytoDyn intends to submit its final study protocol to the FDA, engage a clinical research organization, and complete preparatory work to initiate the phase 2 trial.

The FDA met with biotechnology company, 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 (TAS-102; Lonsurf) and bevacizumab (Avastin) in patients with CCR5+, microsatellite stable (MSS), relapsed/refractory metastatic colorectal cancer (mCRC), according to a news release from CytoDyn, the developer.¹

CytoDyn intends to submit its final study protocol to the FDA, formally engage a clinical research organization (CRO), and complete preparatory work towards initiating the proposed phase 2 trial.

“We are pleased to have received the FDA’s feedback on our phase II study of leronlimab in patients with relapsed/refractory microsatellite stable colorectal cancer, and remain on track to commence our oncology trial in the coming months. Advancing leronlimab in the oncology indication has been an important priority for our team as we progress CytoDyn’s clinical pipeline,” Jacob Lalezari, MD, CEO of CytoDyn, stated in a news release on the meeting.¹

The open-label, multicenter phase 2 trial will randomly assign patients 1:1 to receive either 350 mg or 700 mg of leronlimab in combination with TAS-102 and bevacizumab. The trial will evaluate antitumor activity of the regimen in approximately 60 patients with CCR5+ MSS mCRC.

Leronlimab will be administered weekly and trifluridine plus tipiracil along with bevacizumab will be administered for 3 or 4 weeks in a 4-week cycle. A 5-patient safety lead-in in the 350 mg leronlimab arm will precede enrollment in the 700 mg leronlimab arm.

Eligibility for enrollment in the trial included having measurable disease and having received prior fluoropyrimidine‐, oxaliplatin‐, and irinotecan‐based chemotherapy, an anti‐VEGF therapy, and an anti-EGFR therapy if medically appropriate and is RAS wild‐type. An immunohistochemistry assay will determine CCR5 tumor expression and IHC or next-generation sequencing will confirm MSS CRC diagnosis.

According to a pooled analysis study presented at the 2022 American Society of Clinical Oncology (ASCO) Meeting, leronlimab in use with patients with metastatic triple negative breast cancer (TNBC) was associated with a high clinical benefit, including longer progression-free survival (PFS) and overall survival (OS) with low treatment-emergent adverse event (TEAE) occurrence.²

Patients in the analysis study were pooled from 3 prospective studies: a phase 1b/2 dose escalation (NCT03838367; n =10); compassionate use (NCT04313075; n = 16); and a basket study (NCT04504942; n = 2). Across all 3 studies, patients 1 to 33 doses of leronlimab at either 350 mg, 525 mg, or 700 mg. Patients enrolled had 1 or more prior systemic metastatic TNBC therapies and had either visceral metastases or brain metastases.

Results from the study showed a median PFS of 3.8 months (95% CI, 2.3-6.2) and a median OS of 6.6 months (95% CI, 4.9-not evaluable [NE]) across all patient cohorts. In patients treated with 525 mg or 700 mg leronlimab (n = 19), median PFS was 6.1 months (95% CI, 2.3-7.5) and the median OS was more than 12 months (95% CI, 5.5-12+).

Across all studies, 68 any-grade TEAEs were observed, including 7 grade 1 or 2 AEs and 1 grade 3 AE related to treatment with leronlimab.

References

1. 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 August 13, 2024. https://tinyurl.com/3yc2am7s
2. 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.e1306