Hi Misiu143
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What Does Agenus Tell Us About the ORR Bar for Leronlimab?
The Agenus BOT/BAL results are probably one of the more useful comparisons when thinking about what CytoDyn's CLOVER trial needs to demonstrate in refractory MSS colorectal cancer.
Agenus's trials were not small. Its Phase 1b CRC program enrolled approximately 123 patients, and its randomized Phase 2 enrolled 234 patients. Earlier Agenus data showed an ORR around 23% in evaluable patients without active liver metastases, while the selected BOT/BAL arm in Phase 2 reported a **19.4% ORR (12/62)**.
Those are impressive numbers. Yet the FDA discouraged Agenus from pursuing Accelerated Approval based on the available data because the agency was concerned that objective responses might not ultimately translate into a survival benefit. That is an important lesson for CytoDyn: **ORR alone may not be enough.**
However, I don't believe this means leronlimab has to beat Agenus's **19.4% ORR** to demonstrate a successful CLOVER trial. Agenus itself has described response rates for existing late-line therapies in this population as approximately **1%–6.1%**. That is a much more appropriate starting benchmark.
For CLOVER, I would view roughly **10–15% ORR as clinically meaningful**, **15–20% as very strong**, and **20%+ as exceptional**, assuming the responses are durable and supported by the other endpoints.
There is also an extremely important difference between Agenus and CLOVER: **liver metastases**. Agenus focused its development program on patients without active liver metastases. If CLOVER includes a meaningful number of patients with liver metastases, leronlimab could potentially produce a lower raw ORR than Agenus while still demonstrating a very compelling clinical result in a more difficult population.
That's why I wouldn't judge CLOVER on ORR alone. I would look at the complete package: **ORR, disease control rate, duration of response, PFS, overall survival, ctDNA changes, safety, and particularly how patients with liver metastases perform.**
For example, if CLOVER produced a **14–16% ORR together with strong disease control, substantial ctDNA reductions, durable responses and encouraging PFS/OS—including activity in patients with liver metastases—I would consider that a very strong result.**
The real lesson from Agenus isn't that **19.4% is the number leronlimab must beat**. The lesson is that whatever response rate leronlimab produces needs to be backed by evidence that those responses are durable and ultimately meaningful to patients. If CLOVER can demonstrate that, the results could become considerably more important to both the FDA and a potential pharmaceutical partner.
Please remember I use my AI
What Does Agenus Tell Us About the ORR Bar for Leronlimab?
The Agenus BOT/BAL results are probably one of the more useful comparisons when thinking about what CytoDyn's CLOVER trial needs to demonstrate in refractory MSS colorectal cancer.
Agenus's trials were not small. Its Phase 1b CRC program enrolled approximately 123 patients, and its randomized Phase 2 enrolled 234 patients. Earlier Agenus data showed an ORR around 23% in evaluable patients without active liver metastases, while the selected BOT/BAL arm in Phase 2 reported a **19.4% ORR (12/62)**.
Those are impressive numbers. Yet the FDA discouraged Agenus from pursuing Accelerated Approval based on the available data because the agency was concerned that objective responses might not ultimately translate into a survival benefit. That is an important lesson for CytoDyn: **ORR alone may not be enough.**
However, I don't believe this means leronlimab has to beat Agenus's **19.4% ORR** to demonstrate a successful CLOVER trial. Agenus itself has described response rates for existing late-line therapies in this population as approximately **1%–6.1%**. That is a much more appropriate starting benchmark.
For CLOVER, I would view roughly **10–15% ORR as clinically meaningful**, **15–20% as very strong**, and **20%+ as exceptional**, assuming the responses are durable and supported by the other endpoints.
There is also an extremely important difference between Agenus and CLOVER: **liver metastases**. Agenus focused its development program on patients without active liver metastases. If CLOVER includes a meaningful number of patients with liver metastases, leronlimab could potentially produce a lower raw ORR than Agenus while still demonstrating a very compelling clinical result in a more difficult population.
That's why I wouldn't judge CLOVER on ORR alone. I would look at the complete package: **ORR, disease control rate, duration of response, PFS, overall survival, ctDNA changes, safety, and particularly how patients with liver metastases perform.**
For example, if CLOVER produced a **14–16% ORR together with strong disease control, substantial ctDNA reductions, durable responses and encouraging PFS/OS—including activity in patients with liver metastases—I would consider that a very strong result.**
The real lesson from Agenus isn't that **19.4% is the number leronlimab must beat**. The lesson is that whatever response rate leronlimab produces needs to be backed by evidence that those responses are durable and ultimately meaningful to patients. If CLOVER can demonstrate that, the results could become considerably more important to both the FDA and a potential pharmaceutical partner.
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