Tomorrow, Dr. Milana Dolezal is presenting the following poster at the prestigious San Antonio Breast Cancer Symposium starting at 12:30:
https://sabcs.org/events/poster-session-5/
Quote:PS5-02-30
Prolonged survival following PD-L1/PD-1 immune checkpoint inhibitor therapy after leronlimab induced PD-L1 upregulation on cancer-associated macrophage-like cells and circulating tumor cells in patients with metastatic or locally advanced triple-negative breast cancer
Milana V Dolezal, Stanford University School of Medicine, Stanford, CA
View Abstract
M. V. Dolezal1, V. G. Abramson2, N. Chittoria3, S. Ehsani4, R. G. Pestell5, H. S. Rugo6, H. Rui7, D. L. Adams8, J. Meidling9, M. Lataillade9, J. P. Lalezari9; 1Department of Medicine, Stanford University School of Medicine, Stanford, CA, 2Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, 3Department of Medicine, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, 4Department of Medicine, University of Arizona Cancer Center, Tucson, AZ, 5Department of Medicine, Pennsylvania Cancer and Regenerative Medicine Research Center, Wynnewood, PA, 6Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, 7Cancer Biology, Thomas Jefferson University, Philadelphia, PA, 8Department of Clinical R&D, Creatv MicroTech, Inc., Monmouth Junction, NJ, 9Department of R&D, CytoDyn Inc., Vancouver, WA.
Background. Pretreated patients with metastatic triple-negative breast cancer (mTNBC) have a poor prognosis. In clinical trials among previously treated mTNBC patients the median overall survival (mOS) has been reported as 6.6 months for ≥3rd line chemotherapy, 11.8 months for ≥2nd line sacituzumab govitecan, and 9.9 months for ≥1st line pembrolizumab. It has also been reported that in the real-world, after first line therapy around a third of patients die before receiving 2nd line treatment. Furthermore, there remains an unmet need in the PD-L1 negative mTNBC patient population. It has been shown that >95% of TNBCs are positive for C-C chemokine receptor 5 (CCR5). Leronlimab (LRM) is a humanized monoclonal antibody that blocks CCR5 and reduces TNBC metastasis by >98% in preclinical models. Methods. In a retrospective post hoc analysis, data were pooled from 28 patients with mTNBC from 3 LRM clinical trials (NCT03838367 [N=10]; NCT04313075 [N=16]; NCT04504942 [N=2]). LRM was given subcutaneously weekly at a dose of 350 mg (N=10), 525 mg (N=15), or 700 mg (N=3) in combination with various chemotherapies ± immune checkpoint inhibitors (ICI). PD-L1 staining was measured on cancer-associated macrophage-like cells (CAMLs) and circulating tumor cells (CTCs) prior to and after (≈40 days) LRM treatment. Cox proportional univariate analyses were run to determine Hazard Ratios (HRs) for progression-free survival (PFS) and overall survival (OS) at 48 months. Results. Median age was 48.5 years (range 32-83) with a median of 2 prior metastatic therapies (range 0 to ≥3). Overall, 18% (5/28) of patients had PD-L1 positive tumor staining (CPS≥10%). LRM was well tolerated with no patients withdrawing due to LRM-related adverse events and no dose-limiting toxicities. Overall, mPFS was 3.8 months and mOS was 6.8 months. Survival at 1, 2, 3, and 4 years was 35.7%, 21.4%, 17.9%, and 17.9%, respectively. An upregulation from baseline of PD-L1 was observed in CAMLs/CTCs in 76% (16/21) of patients (7 patients had no post-baseline samples) after any dose of LRM, and in 88% (15/17) of patients receiving the 525 mg or 700 mg doses. Sixteen patients showed a drop in CAMLs/CTCs after initiating LRM while 12 showed an increase. The mOS for patients who showed a drop in CAMLs/CTCs was 17.2 months (95% CI, 9.4–N/A) compared to 3.7 months (95% CI, 1.7–5.6) for those patients who showed an increase in CAMLs/CTCs after LRM treatment (HR: 7.11 [95% CI, 2.5–20.2; p=0.0007]). Further, of the seven patients treated with an ICI with, or after LRM, 5/5 (100%) patients with PD-L1 upregulation remained alive at 4 years, compared to none of the 21 patients (0%) who did not receive an ICI with or after LRM (HR: 4.14 [95% CI, 1.7–10.2; p=0.0041]). Conclusions. In this retrospective pooled analysis of 28 mTNBC patients, LRM was well tolerated. A 4-year OS rate of 17.9% (5/28) in a population with a median of 2 prior metastatic therapies is encouraging. Among a key subgroup, all 5 patients with PD-L1 upregulation who subsequently received ICI remained alive at 4 years possibly indicating a correlation with durable responses. A reduction in CAMLs/CTCs after LRM treatment may relate to improved survival, suggesting its potential as a prognostic biomarker. These findings support the hypothesis that LRM may enhance PD-L1 expression on CAMLs/CTCs, potentially priming tumors for improved responses to ICIs. In an evolving treatment landscape these data warrant prospective evaluation of LRM, particularly in combination with ICIs in mTNBC.
https://sabcs.org/events/poster-session-5/
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