For our new investors! What is mTNBC and why is
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Posted On: 05/01/2025 5:07:14 PM
For our new investors!
What is mTNBC and why is survival so poor?
Metastatic triple-negative breast cancer (mTNBC) is an aggressive breast cancer that lacks estrogen, progesterone, and HER2 receptors.
Because it doesn’t have these targets, most treatments rely on chemotherapy, which has limited effectiveness.
Once mTNBC spreads and progresses through first-line treatment, survival times drop sharply.
How long do patients usually live (mOS = median overall survival)?
First-line treatment: ~12–17 months → chemo + immunotherapy (if PD-L1 positive)
Second-line treatment: ~6–9 months → chemo, antibody-drug conjugates like Trodelvy
Third-line and beyond: ~6–6.5 months → mostly chemotherapy, very poor outcomes
So, after first-line failure, survival often drops below 7 months, and new therapies struggle to extend this meaningfully.
What new treatments have improved survival?
Sacituzumab govitecan (Trodelvy):
Antibody-drug conjugate.
Showed mOS ~12 months in late-line patients.
Became a game-changer in second-/third-line mTNBC.
Pembrolizumab + chemo (KEYNOTE-355):
For first-line PD-L1 positive mTNBC.
Increased mOS to ~23 months vs. ~16 with chemo alone.
Atezolizumab + nab-paclitaxel (IMpassion130):
Previously approved; mOS ~25 months in PD-L1+.
Later withdrawn in U.S. after confirmatory failure.
Datopotamab deruxtecan (Dato-DXd):
Early promising data; mOS not fully reported yet.
Where does leronlimab fit in?
Leronlimab (CytoDyn) is an investigational CCR5-blocking antibody.
In a small mTNBC trial (28 patients, chemo-refractory):
4 patients are still alive after ~36 months.
This survival tail is highly unusual in late-line mTNBC, where median survival is ~6 months.
While we don’t yet know the full mOS from this trial, the long-term responders stand out.
Why does this matter?
If leronlimab’s results hold up in larger trials:
It may redefine late-line treatment by offering long-term survival in some patients.
It could join or even exceed the impact of Trodelvy in the mTNBC treatment landscape.
This potential is why many researchers and investors are paying close attention.
Visual recap
The chart I showed compares:
Chemo (late-line): ~6.5 months
Trodelvy: ~12 months
Pembrolizumab + chemo (1st line, PD-L1+): ~23 months
Atezolizumab + nab-paclitaxel (1st line, PD-L1+): ~25 months
Leronlimab: 36+ months (for longest survivors, not median)
Summary
Standard mTNBC survival drops fast after first-line treatment.
Trodelvy set a new benchmark in late-line (~12 months mOS).
Leronlimab shows exceptional long survivors but needs validation.
If confirmed, leronlimab could shift the late-line treatment paradigm.
What is mTNBC and why is survival so poor?
Metastatic triple-negative breast cancer (mTNBC) is an aggressive breast cancer that lacks estrogen, progesterone, and HER2 receptors.
Because it doesn’t have these targets, most treatments rely on chemotherapy, which has limited effectiveness.
Once mTNBC spreads and progresses through first-line treatment, survival times drop sharply.
How long do patients usually live (mOS = median overall survival)?
First-line treatment: ~12–17 months → chemo + immunotherapy (if PD-L1 positive)
Second-line treatment: ~6–9 months → chemo, antibody-drug conjugates like Trodelvy
Third-line and beyond: ~6–6.5 months → mostly chemotherapy, very poor outcomes
So, after first-line failure, survival often drops below 7 months, and new therapies struggle to extend this meaningfully.
What new treatments have improved survival?
Sacituzumab govitecan (Trodelvy):
Antibody-drug conjugate.
Showed mOS ~12 months in late-line patients.
Became a game-changer in second-/third-line mTNBC.
Pembrolizumab + chemo (KEYNOTE-355):
For first-line PD-L1 positive mTNBC.
Increased mOS to ~23 months vs. ~16 with chemo alone.
Atezolizumab + nab-paclitaxel (IMpassion130):
Previously approved; mOS ~25 months in PD-L1+.
Later withdrawn in U.S. after confirmatory failure.
Datopotamab deruxtecan (Dato-DXd):
Early promising data; mOS not fully reported yet.
Where does leronlimab fit in?
Leronlimab (CytoDyn) is an investigational CCR5-blocking antibody.
In a small mTNBC trial (28 patients, chemo-refractory):
4 patients are still alive after ~36 months.
This survival tail is highly unusual in late-line mTNBC, where median survival is ~6 months.
While we don’t yet know the full mOS from this trial, the long-term responders stand out.
Why does this matter?
If leronlimab’s results hold up in larger trials:
It may redefine late-line treatment by offering long-term survival in some patients.
It could join or even exceed the impact of Trodelvy in the mTNBC treatment landscape.
This potential is why many researchers and investors are paying close attention.
Visual recap
The chart I showed compares:
Chemo (late-line): ~6.5 months
Trodelvy: ~12 months
Pembrolizumab + chemo (1st line, PD-L1+): ~23 months
Atezolizumab + nab-paclitaxel (1st line, PD-L1+): ~25 months
Leronlimab: 36+ months (for longest survivors, not median)
Summary
Standard mTNBC survival drops fast after first-line treatment.
Trodelvy set a new benchmark in late-line (~12 months mOS).
Leronlimab shows exceptional long survivors but needs validation.
If confirmed, leronlimab could shift the late-line treatment paradigm.
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