Flexible design Changing dosing intervals/dosage is a common practice to find an effective treatment yet with acceptable safety and Cybrexa's PDC currently investigated by the same investigator as TH1902 shows the initial design can change multiple times in order to get the recommended dosage for next stage and if the results are positive companies can get accelerated approval for the hard to treat cancer patients. Point is changing dosages or and dosing intervals is not unusual and not indicative of failure specifically during the early stages of clinical trials.
"The focus of this study is to see [whether] we can develop a strategy to deliver higher levels of chemotherapy to cancer cells out of proportion to normal cells using a novel strategy; this is taking advantage of the fact that cancer cells have an active metabolism creating [an] acidic microenvironment..
This was an all-comer phase 1 study, we enrolled a lot of patients who were heavily pretreated. It was a 3 + 3 dose-escalation design exploring more than 1 schedule. We initially started with a schedule of 5 days in a row every 3 weeks, and that was not tolerated; we had quite a bit of neutropenia and thrombocytopenia. Then we explored 2 separate dosing schedules [of CBX-12] given 3 days in a row every 3 weeks vs a [once] weekly schedule. This is a study that’s ongoing and we have a potential dose in the 3 days in a row every 3 weeks [arrangement], but we’re still refining the weekly schedule and currently we’re also exploring a once every 3 weeks schedule."
https://www.onclive.com/view/early-data-signal-response-with-cbx-12-in-advanced-or-metastatic-solid-tumors