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Posted On: 05/07/2025 6:06:53 PM
Post# of 152836
Here's the abstract from the Munich conference:
Background
CCR5 is a G protein-coupled receptor that is overexpressed in ∼95% of TNBC. Leronlimab, a humanized monoclonal antibody to CCR5, blocked CCR5-mediated signaling, and reduced TNBC metastasis by >98% in mice. Pretreated mTNBC has a poor prognosis whether treated with chemotherapy (French ESME program, ≥2 systemic therapies, median overall survival (mOS) ∼6 months, survival 1 year ∼25%, 2 years ∼10%, 3 years ∼7%), pembrolizumab + standard chemotherapy (mOS=10.8 months, 1 year ∼25%, 2 years 10%), or sacituzumab govitecan (ASCENT) (mOS=∼11.8 months, 1 year ∼25%, 2 years 20%).
Methods
28 patients with mTNBC were treated across three leronlimab clinical trials ((NCT03838367, N=10), (NCT04313075, N=16), (NCT04504942, N=2)). Treatment on NCT03838367 included leronlimab and carboplatin. NCT04313075, and NCT04504942 allowed physician’s choice treatment with chemotherapy and immune therapy. SC leronlimab was administered weekly (350mg (n=10), 525mg (n=15) or 700mg (n=3)).
Results
The patient characteristics: median age, 48.5 yrs (32-83;N=28), prior lines of systemic therapy (median=3), visceral metastases (29% (N=
), non-visceral metastases (64% (N=18)) of which (N= had brain metastases, unknown (n=2). Leronlimab was well tolerated, with few adverse events related to leronlimab treatment (TRAEs) (5 grade 1, 2 grade 2), in addition to AEs from chemotherapy. No patients withdrew due to leronlimab TRAEs. No DLTs were observed in NCT03838367 after dose escalation to 700 mg (n=10). Pooled analysis of the 3 studies showed from time of leronlimab treatment; mOS 6.8 months (95% CI: 4.4-17.7), survival at 1 yr. 41.3% (95% CI 22.7-59., 2 yr. 24.8% (95% CI:8.0-41.5), and 3 yr. 19.8% (95% CI: 3.8-35.8%). 4 patients who are currently alive without evidence of disease after 42, 48, 49, and 52, months, each had 4 prior lines of systemic therapy and were treated with leronlimab either in combination or subsequently, with checkpoint inhibitors: pembrolizumab (N=1) or atezolizumab (N=3) and chemotherapy (N=4).
Conclusions
Leronlimab was well-tolerated. The encouraging pooled survival (1 yr. 41.3%, 2 yr. 24.8%, 3 yr 19.8%) suggests further studies in patients with mTNBC are warranted.
Clinical trial identification
NCT03838367, NCT04313075, NCT04504942.
Legal entity responsible for the study
CytoDyn Inc.
Funding
CytoDyn Inc.
Disclosure
R.G. Pestell: Financial Interests, Institutional, Stocks/Shares, consultant: CytoDyn; Financial Interests, Personal and Institutional, Ownership Interest: EcoGenome, LightSeed, StromaGenesis, ioROC, Shenandoah. M. Cristofanilli: Financial Interests, Personal, Advisory Role: Lilly, Sermonix, Foundation Medicine, Guardant Health, Celcuity, Iylon, Ellipses; Financial Interests, Personal and Institutional, Research Grant: Pfizer , Menarini. D. Adams: Financial Interests, Personal, Leadership Role: Creatv MicroTech, Inc. M. Dolezal: Financial Interests, Personal, Advisory Role: AstraZeneca . H. Rui: Financial Interests, Personal, Advisory Role: CytoDyn Inc, miRoncol Diagnostics ; Financial Interests, Personal, Ownership Interest: Advantex Bioreagents, IHG Biosciences. C. Arman, M. Joseph, B. Cunningham, J. Lalezari: Financial Interests, Personal, Full or part-time Employment: CytoDyn Inc. H.S. Rugo: Financial Interests, Personal, Advisory Board, Consultancy/advisory support: NAPO; Financial Interests, Personal, Invited Speaker, Honoraria: Mylan/Viatris, Chugai; Financial Interests, Personal, Advisory Board, Advisory/Consultancy: PUMA, Sanofi; Financial Interests, Personal, Other, Advisory/Consultant: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Daiichi, AstraZeneca, Gilead Sciences, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx.
Background
CCR5 is a G protein-coupled receptor that is overexpressed in ∼95% of TNBC. Leronlimab, a humanized monoclonal antibody to CCR5, blocked CCR5-mediated signaling, and reduced TNBC metastasis by >98% in mice. Pretreated mTNBC has a poor prognosis whether treated with chemotherapy (French ESME program, ≥2 systemic therapies, median overall survival (mOS) ∼6 months, survival 1 year ∼25%, 2 years ∼10%, 3 years ∼7%), pembrolizumab + standard chemotherapy (mOS=10.8 months, 1 year ∼25%, 2 years 10%), or sacituzumab govitecan (ASCENT) (mOS=∼11.8 months, 1 year ∼25%, 2 years 20%).
Methods
28 patients with mTNBC were treated across three leronlimab clinical trials ((NCT03838367, N=10), (NCT04313075, N=16), (NCT04504942, N=2)). Treatment on NCT03838367 included leronlimab and carboplatin. NCT04313075, and NCT04504942 allowed physician’s choice treatment with chemotherapy and immune therapy. SC leronlimab was administered weekly (350mg (n=10), 525mg (n=15) or 700mg (n=3)).
Results
The patient characteristics: median age, 48.5 yrs (32-83;N=28), prior lines of systemic therapy (median=3), visceral metastases (29% (N=
), non-visceral metastases (64% (N=18)) of which (N= had brain metastases, unknown (n=2). Leronlimab was well tolerated, with few adverse events related to leronlimab treatment (TRAEs) (5 grade 1, 2 grade 2), in addition to AEs from chemotherapy. No patients withdrew due to leronlimab TRAEs. No DLTs were observed in NCT03838367 after dose escalation to 700 mg (n=10). Pooled analysis of the 3 studies showed from time of leronlimab treatment; mOS 6.8 months (95% CI: 4.4-17.7), survival at 1 yr. 41.3% (95% CI 22.7-59., 2 yr. 24.8% (95% CI:8.0-41.5), and 3 yr. 19.8% (95% CI: 3.8-35.8%). 4 patients who are currently alive without evidence of disease after 42, 48, 49, and 52, months, each had 4 prior lines of systemic therapy and were treated with leronlimab either in combination or subsequently, with checkpoint inhibitors: pembrolizumab (N=1) or atezolizumab (N=3) and chemotherapy (N=4). Conclusions
Leronlimab was well-tolerated. The encouraging pooled survival (1 yr. 41.3%, 2 yr. 24.8%, 3 yr 19.8%) suggests further studies in patients with mTNBC are warranted.
Clinical trial identification
NCT03838367, NCT04313075, NCT04504942.
Legal entity responsible for the study
CytoDyn Inc.
Funding
CytoDyn Inc.
Disclosure
R.G. Pestell: Financial Interests, Institutional, Stocks/Shares, consultant: CytoDyn; Financial Interests, Personal and Institutional, Ownership Interest: EcoGenome, LightSeed, StromaGenesis, ioROC, Shenandoah. M. Cristofanilli: Financial Interests, Personal, Advisory Role: Lilly, Sermonix, Foundation Medicine, Guardant Health, Celcuity, Iylon, Ellipses; Financial Interests, Personal and Institutional, Research Grant: Pfizer , Menarini. D. Adams: Financial Interests, Personal, Leadership Role: Creatv MicroTech, Inc. M. Dolezal: Financial Interests, Personal, Advisory Role: AstraZeneca . H. Rui: Financial Interests, Personal, Advisory Role: CytoDyn Inc, miRoncol Diagnostics ; Financial Interests, Personal, Ownership Interest: Advantex Bioreagents, IHG Biosciences. C. Arman, M. Joseph, B. Cunningham, J. Lalezari: Financial Interests, Personal, Full or part-time Employment: CytoDyn Inc. H.S. Rugo: Financial Interests, Personal, Advisory Board, Consultancy/advisory support: NAPO; Financial Interests, Personal, Invited Speaker, Honoraria: Mylan/Viatris, Chugai; Financial Interests, Personal, Advisory Board, Advisory/Consultancy: PUMA, Sanofi; Financial Interests, Personal, Other, Advisory/Consultant: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Daiichi, AstraZeneca, Gilead Sciences, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx.
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