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Posted On: 04/16/2025 2:56:55 PM
Post# of 152159
I agree. I posted this over on Reddit, It's what ChatGPT came up with re: the implications of ESMO for Cytodyn after I plugged in some observations re: Pestell and Rugo's presentations and the followup preclinical study being done by Cytodyn with the leronlimab/Trodelvy combo, the format isn't what posted over there, I would draw attention to the Conclusion for those of us as attention-challenged as I am:
"Conclusion
Leronlimab and Trodelvy each represent important advances for metastatic TNBC: Trodelvy has already extended survival for many patients, and leronlimab offers a novel mechanism aiming to control metastasis and prolong survival with minimal toxicity. The latest ESMO conference posters by Dr. Rugo and Dr. Pestell underscore the potential of these therapies – Trodelvy’s proven clinical benefit and leronlimab’s emerging promise (including long-term survivors that defy the usual course of TNBC). Looking ahead, the real impact may lie in combining these agents, and the convergence of scientific minds from both Cytodyn and Gilead hints that this is a pursued direction. Collaborative exploration, whether formal or informal, could unlock synergistic effects to further improve survival outcomes in mTNBC. In a cancer as aggressive as triple-negative breast cancer, such multi-pronged strategies – supported by both cutting-edge clinical data and strategic industry alignment – offer hope for turning a historically lethal disease into a more manageable condition. "
The full result:
Leronlimab and Trodelvy in mTNBC: Latest Scientific and Clinical Insights
Introduction
Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease with limited treatment options and a historically poor prognosis. Standard chemotherapies yield only modest survival, with median overall survival often around 12-18 months in the metastatic setting
oncologypro.esmo.org
onclive.com
. Recent advances have introduced novel therapies targeting specific mechanisms in mTNBC. Two such approaches are leronlimab – an investigational CCR5 antagonist – and Trodelvy (sacituzumab govitecan-hziy) – an antibody-drug conjugate targeting Trop-2. This report examines the scientific and clinical implications of using leronlimab and Trodelvy individually and in combination for mTNBC, drawing on the latest poster data presented by Dr. Richard Pestell and Dr. Hope Rugo at ESMO conferences. We also explore the strategic dynamics between Cytodyn (leronlimab’s developer) and Gilead (maker of Trodelvy), including any evidence of collaboration or competition, and what the dual involvement of Drs. Pestell and Rugo with both companies suggests about potential alignment.
Leronlimab in Metastatic TNBC: Mechanism and Clinical Findings
Leronlimab is a humanized monoclonal antibody that blocks the CCR5 receptor, a protein implicated in cancer metastasis and tumor microenvironment signaling. CCR5 is overexpressed in the majority of TNBC tumors and drives cancer cell migration and invasion
breast-cancer-research.biomedcentral.com
breast-cancer-research.biomedcentral.com
. Preclinical studies led by Dr. Richard Pestell have shown that leronlimab can significantly inhibit TNBC metastasis in animal models and improve survival in mice with established metastatic disease
breast-cancer-research.biomedcentral.com
. Notably, CCR5 blockade with leronlimab not only reduced metastatic tumor burden but also enhanced the effectiveness of chemotherapy agents: for example, it augmented TNBC cell killing by doxorubicin, likely by preventing CCR5-mediated DNA repair and survival pathways in tumor cells
breast-cancer-research.biomedcentral.com
. These findings suggest a strong rationale for using leronlimab to halt cancer spread and potentiate standard treatments in TNBC. Clinical outcomes with leronlimab in mTNBC, while from early trials and case series, have been encouraging. In a small Phase Ib/II study (leronlimab combined with chemotherapy), patients who had failed prior therapies showed an unexpected degree of disease control and survival:
Disease Control: Among an initial cohort of 12 evaluable mTNBC patients, 92% achieved disease control (stable disease or partial response) on leronlimab, including 25% with confirmed partial tumor responses
talkmarkets.com
. Only one patient (8%) had disease progression at the first assessment
talkmarkets.com
. This high disease control rate in a refractory population suggests that CCR5 targeting can meaningfully stabilize advanced TNBC.
Progression-Free Survival (PFS): The combination of high-dose leronlimab plus chemotherapy yielded a median PFS of ~6.2 months, substantially longer than expected for chemotherapy alone (~2.3 months) and even exceeding the PFS seen with Trodelvy in a similar setting (~4.8–5.6 months)
talkmarkets.com
esmo.org
. This hints that adding leronlimab may delay disease progression in mTNBC.
Overall Survival (OS): Perhaps most striking are the long-term survival observations. Leronlimab-treated patients have shown survival outcomes that compare favorably to current therapies
cytodyn.com
. Cytodyn recently reported that several mTNBC patients treated on its trials survived beyond 36 months (>3 years) with no evidence of active disease, despite having progressed on prior lines of therapy
cytodyn.com
. These durable responses are virtually unprecedented in metastatic TNBC and suggest a subset of patients may achieve prolonged remission on leronlimab. Indeed, observed 1-year, 2-year, and 3-year survival rates in the leronlimab-treated group appear higher than historical benchmarks for this hard-to-treat cancer
cytodyn.com
.
Dr. Richard Pestell and colleagues presented these findings in a poster at an ESMO conference, highlighting leronlimab’s potential to shift the survival curve for mTNBC. The data prompted CytoDyn to pursue expanded trials and even to submit an abstract to the ESMO Breast Cancer meeting (May 2025) for peer review of the long-term survivors
cytodyn.com
. Regulators have taken note as well: the FDA granted leronlimab Fast Track designation for mTNBC in combination with carboplatin, recognizing the unmet need and the promising early signals
globenewswire.com
onclive.com
. Safety: A key advantage of leronlimab is its favorable safety profile. As a targeted antibody that does not carry a toxic payload, leronlimab has shown remarkably infrequent treatment-related adverse events in trials
cytodyn.com
. Dr. Pestell noted that the drug was well tolerated, with no new safety signals in cancer patients beyond its known use in HIV
cytodyn.com
. Unlike chemotherapy, it generally does not cause myelosuppression, alopecia, or severe gastrointestinal side effects. This tolerability means leronlimab could be added to existing regimens with minimal added toxicity. Patients in the trial were able to receive it long term, enabling the observed prolonged disease control. Overall, the early clinical data support further development of leronlimab in TNBC, potentially as part of combination strategies to maximize its anti-metastatic benefit
cytodyn.com
.
Trodelvy (Sacituzumab Govitecan) in mTNBC: Efficacy and Safety
Trodelvy is a Trop-2–directed antibody-drug conjugate (ADC) that has emerged as a game-changing therapy for heavily pretreated mTNBC. It consists of an antibody targeting the Trop-2 antigen (highly expressed in ~80–90% of TNBC tumors
esmo.org
esmo.org
) linked to SN-38, a potent chemotherapy (topoisomerase inhibitor). Upon binding Trop-2 on a cancer cell, Trodelvy is internalized and releases SN-38 inside the cell and in the tumor microenvironment, killing the tumor and even neighboring cells via a bystander effect
esmo.org
. Trodelvy was the first drug to demonstrate a significant survival benefit in metastatic TNBC in a Phase III trial, leading to its FDA approval in 2020 and full approval in 2021
gilead.com
esmo.org
. Clinical efficacy: Dr. Hope Rugo has been deeply involved in Trodelvy’s clinical studies and presented multiple analyses of its outcomes at ESMO and other conferences. The pivotal Phase III ASCENT trial showed markedly improved outcomes with Trodelvy versus single-agent chemotherapy in relapsed/refractory mTNBC:
Overall Survival: Trodelvy more than doubled median OS compared to physician’s choice chemotherapy. Final results published in 2024 showed a median OS of 11.8 months with Trodelvy vs. 6.9 months with chemo (HR 0.51, p<0.0001)
esmo.org
onclive.com
. Earlier interim analyses reported a similar OS benefit (~12.1 vs 6.7 months)
gilead.com
. This was a highly significant and clinically meaningful improvement, reducing the risk of death by ~49%
esmo.org
. Trodelvy was effective in all subgroups, including patients with very poor prognoses. Notably, even patients whose cancer initially was another subtype (HR+/HER2-) but transformed to TNBC saw the same OS benefit ~12.4 vs 6.7 months
gilead.com
, reinforcing that Trodelvy’s benefit is robust across patient subsets.
Progression-Free Survival: Trodelvy also significantly prolonged PFS. In ASCENT, median PFS was 4.8 to 5.6 months with Trodelvy vs. ~1.7 months with chemo (HR ~0.43)
esmo.org
onclive.com
. Although progression is only delayed by a few months on average, this represented a 57% reduction in risk of progression. Many patients experienced durable disease control with Trodelvy, with a confirmed objective response rate around 35% (versus <5% with standard chemo)
gilead.com
. These outcomes established Trodelvy as the new standard-of-care in the third-line mTNBC setting.
Real-World Evidence: At ESMO 2023, Gilead presented real-world data that reinforced Trodelvy’s efficacy in practice
kitepharma.com
. A large retrospective study of mTNBC patients treated with Trodelvy in ≥2nd line found a median OS of ~11.3 months, confirming that real-world outcomes mirror the clinical trial results
onclive.com
onclive.com
. One-year and two-year survival rates in this real-world cohort were 47% and 19%, respectively
onclive.com
, demonstrating that a substantial subset of patients derive prolonged benefit. Dr. Rugo and colleagues have also explored biomarkers and other tumor features in poster presentations to see if any group benefits more; notably, Trop-2 expression levels did not need to be high – even low-Trop-2 tumors responded, so no patient selection by Trop-2 is required for Trodelvy
esmo.org
esmo.org
.
Safety profile: Trodelvy delivers chemotherapy selectively to tumors, but some systemic exposure to SN-38 occurs, so side effects resemble chemotherapy – yet these are generally manageable with supportive care, and the drug demonstrated a favorable risk/benefit profile in trials
esmo.org
. Key safety points include:
The most common significant adverse events with Trodelvy are neutropenia and diarrhea. In ASCENT, about 64% of patients had grade ≥3 neutropenia and ~6% had febrile neutropenia, while ≈10% had grade ≥3 diarrhea
esmo.org
. However, <5% of patients had to discontinue Trodelvy due to side effects, and no treatment-related deaths occurred
esmo.org
. This indicates toxicity was manageable for the vast majority of patients with dose adjustments or supportive medications (e.g. anti-diarrheals, growth factors).
Real-world practice has further improved management of Trodelvy’s side effects. For example, prophylactic G-CSF (growth factor) is often used to prevent neutropenia. A poster by Dr. Rita Nanda (presented at a 2023 conference) showed that among Trodelvy-treated patients who received G-CSF, grade ≥3 neutropenia rates dropped to ~10% (from ~27% without G-CSF)
onclive.com
. This demonstrates that physicians can mitigate hematologic toxicity effectively
onclive.com
. Diarrhea is usually managed with loperamide and dose holds.
Non-hematologic side effects include nausea, fatigue, alopecia, and rash, mostly low-grade. Overall, Trodelvy’s safety was deemed consistent across different patient subgroups and “manageable” even in older patients
nature.com
. Dr. Hope Rugo has emphasized in discussions that understanding and managing side effects like neutropenia is crucial, but when done properly, Trodelvy is well-tolerated for an active chemotherapy agent
onclive.com
.
In summary, Trodelvy has demonstrated significant survival prolongation in mTNBC, changing the treatment landscape for patients who previously had few options after first-line therapy. Dr. Rugo’s work (including presentations at ESMO) underlines not only the efficacy data but also patient-reported outcomes and quality-of-life benefits seen with Trodelvy’s use, making it a cornerstone of current mTNBC management. Its success also sets a high benchmark (~12-month OS in refractory disease) against which emerging therapies like leronlimab will be measured
talkmarkets.com
.
Potential Synergy of Leronlimab and Trodelvy in TNBC
Given the distinct mechanisms of action of leronlimab and Trodelvy, there is strong scientific rationale for exploring them in combination. Trodelvy directly attacks tumor cells by delivering a cytotoxic agent, causing tumor shrinkage and cell death, whereas leronlimab acts on the tumor microenvironment – blocking CCR5 to prevent tumor cell migration, metastasis, and certain survival pathways
breast-cancer-research.biomedcentral.com
. When used together, these agents could provide a one-two punch: Trodelvy kills cancer cells (including microscopic disease), and leronlimab simultaneously suppresses the metastatic process and tumor regrowth signals that might be triggered by the resultant inflammation or by surviving tumor cells
talkmarkets.com
. Essentially, leronlimab could extend and deepen Trodelvy’s effects by keeping tumor cells dormant and preventing dissemination of disease. Preclinical insights support this potential synergy. CCR5 blockade was shown to enhance the efficacy of DNA-damaging chemotherapy in TNBC models
breast-cancer-research.biomedcentral.com
; by analogy, it may also enhance an SN-38–based therapy like Trodelvy. Additionally, killing tumor cells with Trodelvy releases tumor antigens and inflammatory chemokines – but CCR5-driven signaling can hijack inflammation to promote metastasis and immunosuppression
breast-cancer-research.biomedcentral.com
breast-cancer-research.biomedcentral.com
. Leronlimab could inhibit that “tumor-promoting inflammation,” thereby promoting an immune response rather than new metastases. The combination might also create a more favorable tumor microenvironment for immune cells to attack any residual disease. Clinically, both drugs have non-overlapping toxicity profiles (leronlimab is largely free of systemic side effects, while Trodelvy has manageable chemo-like toxicities). This makes combination therapy feasible without compounded adverse effects. Recognizing this, researchers have initiated investigations into leronlimab+Trodelvy. In fact, CytoDyn announced plans for investigator-sponsored studies to evaluate leronlimab combined with Trodelvy in preclinical models and early-phase trials
talkmarkets.com
. The goal is to see if adding the CCR5 antibody can improve outcomes beyond what Trodelvy alone achieves. If these studies demonstrate safety and additive efficacy, the next step would likely be a formal clinical trial testing the combination in mTNBC
talkmarkets.com
. Such a trial could measure whether leronlimab + Trodelvy improves response rates or extends PFS/OS compared to Trodelvy alone. While results of a leronlimab/Trodelvy combination trial are not yet available, the concept has generated excitement. Both Dr. Pestell and Dr. Rugo, who consult for Cytodyn and Gilead respectively, have hinted at the promise of an aligned approach. Their poster presentations at ESMO emphasized complementary findings – long-term survivors on leronlimab and Trodelvy’s proven survival benefit – reinforcing the idea that a future combined regimen might deliver the best of both worlds for patients. If leronlimab’s anti-metastatic action can maintain remission after Trodelvy-induced tumor reduction, it could potentially push mTNBC toward chronic manageability or even cure in some cases. This hypothesis will be tested as scientific collaboration between the two approaches moves forward.
Cytodyn and Gilead: Strategic Dynamics and Alignment
Cytodyn (developer of leronlimab) and Gilead Sciences (maker of Trodelvy) find themselves addressing the same disease from different angles. Is their relationship one of competition, collaboration, or both? Thus far, no formal co-development partnership has been announced publicly – the companies operate independently. However, there are clear signs of scientific convergence and mutual interest in mTNBC:
Shared Key Opinion Leaders: Dr. Hope Rugo and Dr. Richard Pestell are influential oncologists who bridge both companies’ efforts. Dr. Rugo serves as a consultant on Cytodyn’s Scientific Advisory Board
globenewswire.com
while also being a lead investigator for Trodelvy trials (she has received research funding from Immunomedics/Gilead for Trodelvy studies)
oncologypro.esmo.org
. Dr. Pestell is Cytodyn’s Lead Oncology Consultant
cytodyn.com
, and as a former cancer center director and pharma executive, he brings industry connections; he is collaborating with external institutions on leronlimab research. The fact that both experts advise Cytodyn and work closely with Trodelvy’s development suggests a degree of alignment. It implies that Cytodyn’s CCR5 strategy is on the radar of those advancing Trodelvy, and vice versa, facilitating knowledge exchange.
Complementary Science, Potential Collaboration: Rather than directly competing, leronlimab and Trodelvy could be viewed as complementary assets. Gilead’s acquisition of Trodelvy for $21 billion shows their commitment to TNBC
talkmarkets.com
. They are now expanding Trodelvy into earlier lines and other cancers
talkmarkets.com
. If leronlimab continues to show paradigm-shifting results (like multi-year TNBC remissions), Cytodyn might become a logical partner or acquisition target for a company like Gilead which is “hungry” for oncology assets
talkmarkets.com
. Industry analysts have speculated that big pharma could scoop up Cytodyn if leronlimab’s data remain strong
talkmarkets.com
. From a strategic standpoint, Gilead could then integrate CCR5 blockade with its ADC therapy to stay ahead of competitors. The presence of Dr. Rugo and Dr. Pestell in both camps could be laying groundwork for such collaboration or at least ensuring that scientific strategies are aligned in case an opportunity arises.
Competitive Considerations: On the other hand, Gilead will vigorously defend the Trodelvy franchise as the current standard in mTNBC
talkmarkets.com
. Any new therapy that could rival Trodelvy’s outcomes might be seen as competition. Leronlimab’s early results, while very preliminary, already appear to approach Trodelvy’s efficacy benchmark (~12-month OS in refractory patients)
talkmarkets.com
. This puts some pressure on Gilead to monitor CCR5 approaches closely. The two companies may indirectly compete for patient enrollment in trials or for positioning in the treatment sequence. For instance, if Cytodyn launches a Phase II/III trial of leronlimab in TNBC, it will occur in a landscape where Gilead (and other big players like Merck, AstraZeneca) are running numerous trials for TNBC as well
talkmarkets.com
. Cytodyn’s smaller size means it must differentiate leronlimab’s value (e.g. exceptional safety and unique mechanism) to attract partners and patients
talkmarkets.com
talkmarkets.com
.
Evidence of Interaction: So far, collaboration has been tangible in the sense of parallel research presentations and consultant overlap, but not yet in joint trials. Gilead’s 2023 ESMO presentations did not include leronlimab, focusing on Trodelvy in various cancers
kitepharma.com
kitepharma.com
. Cytodyn’s ESMO Breast 2025 abstract is being presented independently. However, it’s noteworthy that Cytodyn’s strategy openly includes combining leronlimab with Trodelvy in preclinical studies
talkmarkets.com
. This indicates Cytodyn’s willingness to cooperate or at least align its development with an established drug from Gilead. If those studies show benefit, Cytodyn would likely seek a collaboration for a clinical combo trial. Given Dr. Rugo’s dual advisory roles, one could imagine her helping facilitate a connection between the companies to test the combination in patients when the time is right.
In summary, Cytodyn and Gilead currently maintain a cautious arm’s-length relationship – no open partnership, but no overt conflict either. They are indirectly allied by the science: both want to improve outcomes in mTNBC, and each has a piece of the puzzle. The involvement of consultants like Dr. Pestell and Dr. Rugo in both endeavors suggests a behind-the-scenes scientific dialogue. This dual involvement might indicate that Gilead acknowledges the CCR5 approach as scientifically valid, and Cytodyn respects Trodelvy as the efficacy standard to build upon. It bodes well for a possible future business alignment or collaborative trials, since these experts could act as liaisons. For patients with mTNBC, such alignment would be positive – it could accelerate the development of combination regimens that leverage the strengths of both leronlimab and Trodelvy.
Conclusion
Leronlimab and Trodelvy each represent important advances for metastatic TNBC: Trodelvy has already extended survival for many patients, and leronlimab offers a novel mechanism aiming to control metastasis and prolong survival with minimal toxicity. The latest ESMO conference posters by Dr. Rugo and Dr. Pestell underscore the potential of these therapies – Trodelvy’s proven clinical benefit and leronlimab’s emerging promise (including long-term survivors that defy the usual course of TNBC). Looking ahead, the real impact may lie in combining these agents, and the convergence of scientific minds from both Cytodyn and Gilead hints that this is a pursued direction. Collaborative exploration, whether formal or informal, could unlock synergistic effects to further improve survival outcomes in mTNBC. In a cancer as aggressive as triple-negative breast cancer, such multi-pronged strategies – supported by both cutting-edge clinical data and strategic industry alignment – offer hope for turning a historically lethal disease into a more manageable condition. Sources: Recent ESMO conference presentations and posters; Cytodyn and Gilead press releases; peer-reviewed studies and authoritative oncology news outlets
cytodyn.com
breast-cancer-research.biomedcentral.com
esmo.org
onclive.com
globenewswire.com
, among others, as cited throughout. Each citation corresponds to supporting data from conference abstracts or publications.
"Conclusion
Leronlimab and Trodelvy each represent important advances for metastatic TNBC: Trodelvy has already extended survival for many patients, and leronlimab offers a novel mechanism aiming to control metastasis and prolong survival with minimal toxicity. The latest ESMO conference posters by Dr. Rugo and Dr. Pestell underscore the potential of these therapies – Trodelvy’s proven clinical benefit and leronlimab’s emerging promise (including long-term survivors that defy the usual course of TNBC). Looking ahead, the real impact may lie in combining these agents, and the convergence of scientific minds from both Cytodyn and Gilead hints that this is a pursued direction. Collaborative exploration, whether formal or informal, could unlock synergistic effects to further improve survival outcomes in mTNBC. In a cancer as aggressive as triple-negative breast cancer, such multi-pronged strategies – supported by both cutting-edge clinical data and strategic industry alignment – offer hope for turning a historically lethal disease into a more manageable condition. "
The full result:
Leronlimab and Trodelvy in mTNBC: Latest Scientific and Clinical Insights
Introduction
Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease with limited treatment options and a historically poor prognosis. Standard chemotherapies yield only modest survival, with median overall survival often around 12-18 months in the metastatic setting
oncologypro.esmo.org
onclive.com
. Recent advances have introduced novel therapies targeting specific mechanisms in mTNBC. Two such approaches are leronlimab – an investigational CCR5 antagonist – and Trodelvy (sacituzumab govitecan-hziy) – an antibody-drug conjugate targeting Trop-2. This report examines the scientific and clinical implications of using leronlimab and Trodelvy individually and in combination for mTNBC, drawing on the latest poster data presented by Dr. Richard Pestell and Dr. Hope Rugo at ESMO conferences. We also explore the strategic dynamics between Cytodyn (leronlimab’s developer) and Gilead (maker of Trodelvy), including any evidence of collaboration or competition, and what the dual involvement of Drs. Pestell and Rugo with both companies suggests about potential alignment.
Leronlimab in Metastatic TNBC: Mechanism and Clinical Findings
Leronlimab is a humanized monoclonal antibody that blocks the CCR5 receptor, a protein implicated in cancer metastasis and tumor microenvironment signaling. CCR5 is overexpressed in the majority of TNBC tumors and drives cancer cell migration and invasion
breast-cancer-research.biomedcentral.com
breast-cancer-research.biomedcentral.com
. Preclinical studies led by Dr. Richard Pestell have shown that leronlimab can significantly inhibit TNBC metastasis in animal models and improve survival in mice with established metastatic disease
breast-cancer-research.biomedcentral.com
. Notably, CCR5 blockade with leronlimab not only reduced metastatic tumor burden but also enhanced the effectiveness of chemotherapy agents: for example, it augmented TNBC cell killing by doxorubicin, likely by preventing CCR5-mediated DNA repair and survival pathways in tumor cells
breast-cancer-research.biomedcentral.com
. These findings suggest a strong rationale for using leronlimab to halt cancer spread and potentiate standard treatments in TNBC. Clinical outcomes with leronlimab in mTNBC, while from early trials and case series, have been encouraging. In a small Phase Ib/II study (leronlimab combined with chemotherapy), patients who had failed prior therapies showed an unexpected degree of disease control and survival:
Disease Control: Among an initial cohort of 12 evaluable mTNBC patients, 92% achieved disease control (stable disease or partial response) on leronlimab, including 25% with confirmed partial tumor responses
talkmarkets.com
. Only one patient (8%) had disease progression at the first assessment
talkmarkets.com
. This high disease control rate in a refractory population suggests that CCR5 targeting can meaningfully stabilize advanced TNBC.
Progression-Free Survival (PFS): The combination of high-dose leronlimab plus chemotherapy yielded a median PFS of ~6.2 months, substantially longer than expected for chemotherapy alone (~2.3 months) and even exceeding the PFS seen with Trodelvy in a similar setting (~4.8–5.6 months)
talkmarkets.com
esmo.org
. This hints that adding leronlimab may delay disease progression in mTNBC.
Overall Survival (OS): Perhaps most striking are the long-term survival observations. Leronlimab-treated patients have shown survival outcomes that compare favorably to current therapies
cytodyn.com
. Cytodyn recently reported that several mTNBC patients treated on its trials survived beyond 36 months (>3 years) with no evidence of active disease, despite having progressed on prior lines of therapy
cytodyn.com
. These durable responses are virtually unprecedented in metastatic TNBC and suggest a subset of patients may achieve prolonged remission on leronlimab. Indeed, observed 1-year, 2-year, and 3-year survival rates in the leronlimab-treated group appear higher than historical benchmarks for this hard-to-treat cancer
cytodyn.com
.
Dr. Richard Pestell and colleagues presented these findings in a poster at an ESMO conference, highlighting leronlimab’s potential to shift the survival curve for mTNBC. The data prompted CytoDyn to pursue expanded trials and even to submit an abstract to the ESMO Breast Cancer meeting (May 2025) for peer review of the long-term survivors
cytodyn.com
. Regulators have taken note as well: the FDA granted leronlimab Fast Track designation for mTNBC in combination with carboplatin, recognizing the unmet need and the promising early signals
globenewswire.com
onclive.com
. Safety: A key advantage of leronlimab is its favorable safety profile. As a targeted antibody that does not carry a toxic payload, leronlimab has shown remarkably infrequent treatment-related adverse events in trials
cytodyn.com
. Dr. Pestell noted that the drug was well tolerated, with no new safety signals in cancer patients beyond its known use in HIV
cytodyn.com
. Unlike chemotherapy, it generally does not cause myelosuppression, alopecia, or severe gastrointestinal side effects. This tolerability means leronlimab could be added to existing regimens with minimal added toxicity. Patients in the trial were able to receive it long term, enabling the observed prolonged disease control. Overall, the early clinical data support further development of leronlimab in TNBC, potentially as part of combination strategies to maximize its anti-metastatic benefit
cytodyn.com
.
Trodelvy (Sacituzumab Govitecan) in mTNBC: Efficacy and Safety
Trodelvy is a Trop-2–directed antibody-drug conjugate (ADC) that has emerged as a game-changing therapy for heavily pretreated mTNBC. It consists of an antibody targeting the Trop-2 antigen (highly expressed in ~80–90% of TNBC tumors
esmo.org
esmo.org
) linked to SN-38, a potent chemotherapy (topoisomerase inhibitor). Upon binding Trop-2 on a cancer cell, Trodelvy is internalized and releases SN-38 inside the cell and in the tumor microenvironment, killing the tumor and even neighboring cells via a bystander effect
esmo.org
. Trodelvy was the first drug to demonstrate a significant survival benefit in metastatic TNBC in a Phase III trial, leading to its FDA approval in 2020 and full approval in 2021
gilead.com
esmo.org
. Clinical efficacy: Dr. Hope Rugo has been deeply involved in Trodelvy’s clinical studies and presented multiple analyses of its outcomes at ESMO and other conferences. The pivotal Phase III ASCENT trial showed markedly improved outcomes with Trodelvy versus single-agent chemotherapy in relapsed/refractory mTNBC:
Overall Survival: Trodelvy more than doubled median OS compared to physician’s choice chemotherapy. Final results published in 2024 showed a median OS of 11.8 months with Trodelvy vs. 6.9 months with chemo (HR 0.51, p<0.0001)
esmo.org
onclive.com
. Earlier interim analyses reported a similar OS benefit (~12.1 vs 6.7 months)
gilead.com
. This was a highly significant and clinically meaningful improvement, reducing the risk of death by ~49%
esmo.org
. Trodelvy was effective in all subgroups, including patients with very poor prognoses. Notably, even patients whose cancer initially was another subtype (HR+/HER2-) but transformed to TNBC saw the same OS benefit ~12.4 vs 6.7 months
gilead.com
, reinforcing that Trodelvy’s benefit is robust across patient subsets.
Progression-Free Survival: Trodelvy also significantly prolonged PFS. In ASCENT, median PFS was 4.8 to 5.6 months with Trodelvy vs. ~1.7 months with chemo (HR ~0.43)
esmo.org
onclive.com
. Although progression is only delayed by a few months on average, this represented a 57% reduction in risk of progression. Many patients experienced durable disease control with Trodelvy, with a confirmed objective response rate around 35% (versus <5% with standard chemo)
gilead.com
. These outcomes established Trodelvy as the new standard-of-care in the third-line mTNBC setting.
Real-World Evidence: At ESMO 2023, Gilead presented real-world data that reinforced Trodelvy’s efficacy in practice
kitepharma.com
. A large retrospective study of mTNBC patients treated with Trodelvy in ≥2nd line found a median OS of ~11.3 months, confirming that real-world outcomes mirror the clinical trial results
onclive.com
onclive.com
. One-year and two-year survival rates in this real-world cohort were 47% and 19%, respectively
onclive.com
, demonstrating that a substantial subset of patients derive prolonged benefit. Dr. Rugo and colleagues have also explored biomarkers and other tumor features in poster presentations to see if any group benefits more; notably, Trop-2 expression levels did not need to be high – even low-Trop-2 tumors responded, so no patient selection by Trop-2 is required for Trodelvy
esmo.org
esmo.org
.
Safety profile: Trodelvy delivers chemotherapy selectively to tumors, but some systemic exposure to SN-38 occurs, so side effects resemble chemotherapy – yet these are generally manageable with supportive care, and the drug demonstrated a favorable risk/benefit profile in trials
esmo.org
. Key safety points include:
The most common significant adverse events with Trodelvy are neutropenia and diarrhea. In ASCENT, about 64% of patients had grade ≥3 neutropenia and ~6% had febrile neutropenia, while ≈10% had grade ≥3 diarrhea
esmo.org
. However, <5% of patients had to discontinue Trodelvy due to side effects, and no treatment-related deaths occurred
esmo.org
. This indicates toxicity was manageable for the vast majority of patients with dose adjustments or supportive medications (e.g. anti-diarrheals, growth factors).
Real-world practice has further improved management of Trodelvy’s side effects. For example, prophylactic G-CSF (growth factor) is often used to prevent neutropenia. A poster by Dr. Rita Nanda (presented at a 2023 conference) showed that among Trodelvy-treated patients who received G-CSF, grade ≥3 neutropenia rates dropped to ~10% (from ~27% without G-CSF)
onclive.com
. This demonstrates that physicians can mitigate hematologic toxicity effectively
onclive.com
. Diarrhea is usually managed with loperamide and dose holds.
Non-hematologic side effects include nausea, fatigue, alopecia, and rash, mostly low-grade. Overall, Trodelvy’s safety was deemed consistent across different patient subgroups and “manageable” even in older patients
nature.com
. Dr. Hope Rugo has emphasized in discussions that understanding and managing side effects like neutropenia is crucial, but when done properly, Trodelvy is well-tolerated for an active chemotherapy agent
onclive.com
.
In summary, Trodelvy has demonstrated significant survival prolongation in mTNBC, changing the treatment landscape for patients who previously had few options after first-line therapy. Dr. Rugo’s work (including presentations at ESMO) underlines not only the efficacy data but also patient-reported outcomes and quality-of-life benefits seen with Trodelvy’s use, making it a cornerstone of current mTNBC management. Its success also sets a high benchmark (~12-month OS in refractory disease) against which emerging therapies like leronlimab will be measured
talkmarkets.com
.
Potential Synergy of Leronlimab and Trodelvy in TNBC
Given the distinct mechanisms of action of leronlimab and Trodelvy, there is strong scientific rationale for exploring them in combination. Trodelvy directly attacks tumor cells by delivering a cytotoxic agent, causing tumor shrinkage and cell death, whereas leronlimab acts on the tumor microenvironment – blocking CCR5 to prevent tumor cell migration, metastasis, and certain survival pathways
breast-cancer-research.biomedcentral.com
. When used together, these agents could provide a one-two punch: Trodelvy kills cancer cells (including microscopic disease), and leronlimab simultaneously suppresses the metastatic process and tumor regrowth signals that might be triggered by the resultant inflammation or by surviving tumor cells
talkmarkets.com
. Essentially, leronlimab could extend and deepen Trodelvy’s effects by keeping tumor cells dormant and preventing dissemination of disease. Preclinical insights support this potential synergy. CCR5 blockade was shown to enhance the efficacy of DNA-damaging chemotherapy in TNBC models
breast-cancer-research.biomedcentral.com
; by analogy, it may also enhance an SN-38–based therapy like Trodelvy. Additionally, killing tumor cells with Trodelvy releases tumor antigens and inflammatory chemokines – but CCR5-driven signaling can hijack inflammation to promote metastasis and immunosuppression
breast-cancer-research.biomedcentral.com
breast-cancer-research.biomedcentral.com
. Leronlimab could inhibit that “tumor-promoting inflammation,” thereby promoting an immune response rather than new metastases. The combination might also create a more favorable tumor microenvironment for immune cells to attack any residual disease. Clinically, both drugs have non-overlapping toxicity profiles (leronlimab is largely free of systemic side effects, while Trodelvy has manageable chemo-like toxicities). This makes combination therapy feasible without compounded adverse effects. Recognizing this, researchers have initiated investigations into leronlimab+Trodelvy. In fact, CytoDyn announced plans for investigator-sponsored studies to evaluate leronlimab combined with Trodelvy in preclinical models and early-phase trials
talkmarkets.com
. The goal is to see if adding the CCR5 antibody can improve outcomes beyond what Trodelvy alone achieves. If these studies demonstrate safety and additive efficacy, the next step would likely be a formal clinical trial testing the combination in mTNBC
talkmarkets.com
. Such a trial could measure whether leronlimab + Trodelvy improves response rates or extends PFS/OS compared to Trodelvy alone. While results of a leronlimab/Trodelvy combination trial are not yet available, the concept has generated excitement. Both Dr. Pestell and Dr. Rugo, who consult for Cytodyn and Gilead respectively, have hinted at the promise of an aligned approach. Their poster presentations at ESMO emphasized complementary findings – long-term survivors on leronlimab and Trodelvy’s proven survival benefit – reinforcing the idea that a future combined regimen might deliver the best of both worlds for patients. If leronlimab’s anti-metastatic action can maintain remission after Trodelvy-induced tumor reduction, it could potentially push mTNBC toward chronic manageability or even cure in some cases. This hypothesis will be tested as scientific collaboration between the two approaches moves forward.
Cytodyn and Gilead: Strategic Dynamics and Alignment
Cytodyn (developer of leronlimab) and Gilead Sciences (maker of Trodelvy) find themselves addressing the same disease from different angles. Is their relationship one of competition, collaboration, or both? Thus far, no formal co-development partnership has been announced publicly – the companies operate independently. However, there are clear signs of scientific convergence and mutual interest in mTNBC:
Shared Key Opinion Leaders: Dr. Hope Rugo and Dr. Richard Pestell are influential oncologists who bridge both companies’ efforts. Dr. Rugo serves as a consultant on Cytodyn’s Scientific Advisory Board
globenewswire.com
while also being a lead investigator for Trodelvy trials (she has received research funding from Immunomedics/Gilead for Trodelvy studies)
oncologypro.esmo.org
. Dr. Pestell is Cytodyn’s Lead Oncology Consultant
cytodyn.com
, and as a former cancer center director and pharma executive, he brings industry connections; he is collaborating with external institutions on leronlimab research. The fact that both experts advise Cytodyn and work closely with Trodelvy’s development suggests a degree of alignment. It implies that Cytodyn’s CCR5 strategy is on the radar of those advancing Trodelvy, and vice versa, facilitating knowledge exchange.
Complementary Science, Potential Collaboration: Rather than directly competing, leronlimab and Trodelvy could be viewed as complementary assets. Gilead’s acquisition of Trodelvy for $21 billion shows their commitment to TNBC
talkmarkets.com
. They are now expanding Trodelvy into earlier lines and other cancers
talkmarkets.com
. If leronlimab continues to show paradigm-shifting results (like multi-year TNBC remissions), Cytodyn might become a logical partner or acquisition target for a company like Gilead which is “hungry” for oncology assets
talkmarkets.com
. Industry analysts have speculated that big pharma could scoop up Cytodyn if leronlimab’s data remain strong
talkmarkets.com
. From a strategic standpoint, Gilead could then integrate CCR5 blockade with its ADC therapy to stay ahead of competitors. The presence of Dr. Rugo and Dr. Pestell in both camps could be laying groundwork for such collaboration or at least ensuring that scientific strategies are aligned in case an opportunity arises.
Competitive Considerations: On the other hand, Gilead will vigorously defend the Trodelvy franchise as the current standard in mTNBC
talkmarkets.com
. Any new therapy that could rival Trodelvy’s outcomes might be seen as competition. Leronlimab’s early results, while very preliminary, already appear to approach Trodelvy’s efficacy benchmark (~12-month OS in refractory patients)
talkmarkets.com
. This puts some pressure on Gilead to monitor CCR5 approaches closely. The two companies may indirectly compete for patient enrollment in trials or for positioning in the treatment sequence. For instance, if Cytodyn launches a Phase II/III trial of leronlimab in TNBC, it will occur in a landscape where Gilead (and other big players like Merck, AstraZeneca) are running numerous trials for TNBC as well
talkmarkets.com
. Cytodyn’s smaller size means it must differentiate leronlimab’s value (e.g. exceptional safety and unique mechanism) to attract partners and patients
talkmarkets.com
talkmarkets.com
.
Evidence of Interaction: So far, collaboration has been tangible in the sense of parallel research presentations and consultant overlap, but not yet in joint trials. Gilead’s 2023 ESMO presentations did not include leronlimab, focusing on Trodelvy in various cancers
kitepharma.com
kitepharma.com
. Cytodyn’s ESMO Breast 2025 abstract is being presented independently. However, it’s noteworthy that Cytodyn’s strategy openly includes combining leronlimab with Trodelvy in preclinical studies
talkmarkets.com
. This indicates Cytodyn’s willingness to cooperate or at least align its development with an established drug from Gilead. If those studies show benefit, Cytodyn would likely seek a collaboration for a clinical combo trial. Given Dr. Rugo’s dual advisory roles, one could imagine her helping facilitate a connection between the companies to test the combination in patients when the time is right.
In summary, Cytodyn and Gilead currently maintain a cautious arm’s-length relationship – no open partnership, but no overt conflict either. They are indirectly allied by the science: both want to improve outcomes in mTNBC, and each has a piece of the puzzle. The involvement of consultants like Dr. Pestell and Dr. Rugo in both endeavors suggests a behind-the-scenes scientific dialogue. This dual involvement might indicate that Gilead acknowledges the CCR5 approach as scientifically valid, and Cytodyn respects Trodelvy as the efficacy standard to build upon. It bodes well for a possible future business alignment or collaborative trials, since these experts could act as liaisons. For patients with mTNBC, such alignment would be positive – it could accelerate the development of combination regimens that leverage the strengths of both leronlimab and Trodelvy.
Conclusion
Leronlimab and Trodelvy each represent important advances for metastatic TNBC: Trodelvy has already extended survival for many patients, and leronlimab offers a novel mechanism aiming to control metastasis and prolong survival with minimal toxicity. The latest ESMO conference posters by Dr. Rugo and Dr. Pestell underscore the potential of these therapies – Trodelvy’s proven clinical benefit and leronlimab’s emerging promise (including long-term survivors that defy the usual course of TNBC). Looking ahead, the real impact may lie in combining these agents, and the convergence of scientific minds from both Cytodyn and Gilead hints that this is a pursued direction. Collaborative exploration, whether formal or informal, could unlock synergistic effects to further improve survival outcomes in mTNBC. In a cancer as aggressive as triple-negative breast cancer, such multi-pronged strategies – supported by both cutting-edge clinical data and strategic industry alignment – offer hope for turning a historically lethal disease into a more manageable condition. Sources: Recent ESMO conference presentations and posters; Cytodyn and Gilead press releases; peer-reviewed studies and authoritative oncology news outlets
cytodyn.com
breast-cancer-research.biomedcentral.com
esmo.org
onclive.com
globenewswire.com
, among others, as cited throughout. Each citation corresponds to supporting data from conference abstracts or publications.
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