Excellent question — and highly relevant given t
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Posted On: 05/18/2025 10:09:41 AM
Excellent question — and highly relevant given the recent Leronlimab cancer data.
Here's the key point:
Yes, the original mTNBC trial was limited to 350 mg/week by regulatory constraint — not by scientific consensus on what’s optimal.
Background:
In CytoDyn’s 2020-2021 Phase 1b/2 trial for metastatic triple-negative breast cancer (mTNBC), the 350 mg/week dose was used exclusively. This wasn’t because 350 mg was believed to be the best dose, but because higher doses like 525 mg or 700 mg had not yet been approved for cancer trials at that time.
That dosing limitation was regulatory — due to needing safety data first from HIV and COVID-19 trials before escalating dosage in oncology.
Why That Matters Now:
CytoDyn’s new analysis (2025) is retrospective — looking at PD-L1 expression and survival rates in patients from that earlier 350 mg trial — but their poster at ESMO makes a very important observation:
15 of 17 patients receiving 525 mg or more (in newer trials or under compassionate use) had significant increases in PD-L1.
That increase in PD-L1 is what appears to make tumors more responsive to checkpoint inhibitors (like Keytruda), and is likely part of the mechanism enabling the remarkable 4-year survival in some patients.
Summary:
350 mg/week was not the optimal dose — just the only dose allowed at the time.
CytoDyn now sees 525 mg+ as more effective, especially for PD-L1 upregulation and potential synergy with immunotherapy.
Current and future trials are likely to focus on higher doses, particularly 700 mg, as they explore combination therapy with checkpoint inhibitors.
Here's the key point:
Yes, the original mTNBC trial was limited to 350 mg/week by regulatory constraint — not by scientific consensus on what’s optimal.
Background:
In CytoDyn’s 2020-2021 Phase 1b/2 trial for metastatic triple-negative breast cancer (mTNBC), the 350 mg/week dose was used exclusively. This wasn’t because 350 mg was believed to be the best dose, but because higher doses like 525 mg or 700 mg had not yet been approved for cancer trials at that time.
That dosing limitation was regulatory — due to needing safety data first from HIV and COVID-19 trials before escalating dosage in oncology.
Why That Matters Now:
CytoDyn’s new analysis (2025) is retrospective — looking at PD-L1 expression and survival rates in patients from that earlier 350 mg trial — but their poster at ESMO makes a very important observation:
15 of 17 patients receiving 525 mg or more (in newer trials or under compassionate use) had significant increases in PD-L1.
That increase in PD-L1 is what appears to make tumors more responsive to checkpoint inhibitors (like Keytruda), and is likely part of the mechanism enabling the remarkable 4-year survival in some patients.
Summary:
350 mg/week was not the optimal dose — just the only dose allowed at the time.
CytoDyn now sees 525 mg+ as more effective, especially for PD-L1 upregulation and potential synergy with immunotherapy.
Current and future trials are likely to focus on higher doses, particularly 700 mg, as they explore combination therapy with checkpoint inhibitors.
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