Leronlimab Gets FDA Nod for Phase 2 Microsatellite-Stable CRC Trial
A phase 2 trial will evaluate leronlimab’s safety and efficacy for the treatment of patients with microsatellite stable metastatic colorectal cancer.
US FDA
The FDA has granted clearance for the start of a phase 2 study (NCT06699835) evaluating leronlimab in patients with relapsed/refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
Leronlimab works by targeting CCR5 markers on the tumor.
The open-label, randomized, 2-arm, multicenter trial will evaluate leronlimab’s effect on the overall response rate (ORR), overall survival (OS), safety, and tolerability when combined with trifluridine and tipiracil (TAS-102; Lonsurf) and bevacizumab (Avastin) in patients with CCR5-positive (CCR5+), MSS, relapsed/refractory, mCRC.
The FDA has cleared the initiation of a phase 2 study assessing leronlimab for the potential treatment of patients with MSS relapsed/refractory mCRC.1
The phase 2, open-label, randomized, 2-arm, multicenter study will include patients with CCR5+ MSS mCRC. Patients will receive either leronlimab at a dose of 350 mg in combination with TAS-102 and bevacizumab or a 700 mg dose of leronlimab in combination with TAS-102 and bevacizumab to assess the agent’s effect on ORR, OS, safety and tolerability.2
Enrollment is open to patients aged 18 years and older with a history of treated colorectal cancer with unresectable metastases of the primary colorectal cancer to other organs. If patients are HIV-1 positive, their viral load must be below 50 copies/ml and the patient must be on stable ART for at least 3 months. Patients are required to demonstrate positive tumor expression of CCR5 by immunohistochemistry (IHC), have an expected survival of at least 3 months, have measurable disease per RECIST 1.1, have an ECOG performance status of 0 or 1, and have adequate organ and bone marrow function within 28 days prior to registration.
Adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. Further, patients must be histologically confirmed for MSS colorectal cancer by IHC or next-generation sequencing. Patients must not have received anticancer treatment within the last 4 weeks or at least 5 half-lives prior to treatment.
3D medical illustration of colorectal cancer: © anatomy insider - stock.adobe.com
The primary end point is ORR and secondary end points include treatment-emergent adverse events, defined as events with an onset on or after the first treatment, and duration of response.
This study plans to enroll approximately 60 patients, 30 in each of 2 arms, and has an estimated primary completion date of June 2028.
About Leronlimab
Leronlimab targets CCR5 markers on the tumor.3 Prior findings have already shown leronlimab’s potential in oncology, particularly in metastatic triple-negative breast cancer (mTNBC). According to a pooled analysis of 3 clinical trials presented at the 2022 American Society of Clinical Oncology Annual Meeting looking at 28 patients with mTNBC treated with leronlimab at doses of 350 mg, 525 mg, or 700 mg, the median progression-free survival (PFS) observed was 3.8 months. An OS of 6.6 months was also shown.
In the subset of patients who were given higher doses of leronlimab (525 mg or 700 mg), the median PFS extended to 6.1 months, with OS exceeding 12 months.
Leronlimab was generally well tolerated, with a few grade 3 treatment-emergent adverse events.
References
LifeTracDx® blood test to be performed in key colorectal clinical trial. News release. Creatv Bio. March 27, 025. Accessed March 27, 2025. https://tinyurl.com/4dvt6zj8
A phase 2 study of leronlimab in combination with TAS-102 + bevacizumab in previously treated participants with MCRC. ClinicalTrials.gov. Updated November 21, 2024. Accessed March 27, 2025. https://clinicaltrials.gov/study/NCT06699836?cond=colorectal%20cancer&intr=%20leronlimab%20&rank=1
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
