Something else is the safety and toxicity data. This is a Phase...

Something else is the safety and toxicity data. This is a Phase I trial after all, and sure we have been spoilt by the fact we haven’t seen much toxicity I will be looking for any data around this.

YF has spoken about therapeutic index a number of times and the fact CF33 has the largest he’s seen. So, will we start to see any indications of toxicity in humans in the included cohorts? Or are the dosages still too low? It also begs the question, at what dosages will tolerability issues start to arise for the lead investigators to arrive at RP2D? A key endpoint of this trial.

If we see any indication of efficacy coupled with low toxicity or safety concerns that would be significant. One just has to look at the safety/toxicity data of current standard of care and or therapies being bought for billions to acknowledgment what acceptable levels of toxicity are. They are very very high. But alas, no toxicity and completely safe without efficacy, is worthless.

A few people have mentioned ADCs, they have fetched significant buyouts, they have achieved this because they essential help localise the effects of chemotherapy by adding a monoclonal antibody to take chemo direct to the cancer. In effect increasing efficacy and helping reduce toxicity.

In the trial that led to the approval of Immunomedics (bought out for 21 Bill) main therapy, Sacituzumab govitecan (Trodelvy), the results in TNBC were (see here for journal): The 108 patients with triple-negative breast cancer had received a median of 3 previous therapies. Four deaths occurred during treatment; 3 patients (2.8%) discontinued treatment because of adverse events. Grade 3 or 4 adverse events (in ≥10% of the patients) included anaemia and neutropenia; 10 patients (9.3%) had febrile neutropenia. The response rate (3 complete and 33 partial responses) was 33.3% (95% confidence interval [CI], 24.6 to 43.1), and the median duration of response was 7.7 months.

It’s almost impossible to compare trials like apples but it gives an indication around response rate expectations relative to safety. 4 people died from the treatment and 3 had a complete response from it. This speaks to how desperate we are to find therapies that help kill cancer, especially ones as terrible as TNBC and even if only in a minority of patients.

So yea although it might still be too soon to tell (data released only on early cohorts) if we can see some positive signals and a trend suggesting increased efficacy as dosages increase then we are certainly looking good.

Cheers.