Regulatory Open Forum

Hello RAPS Community,

We are in the process of filing our first IND, and are planning for a Pre-IND. In our Phase 1 FIH study design for a molecularly targeted small molecule we plan to add a dose optimization cohort in dose escalation that is tumor agnostic but will likely compare 2 therapeutic doses, with the goal of identifying the recommended dose for the expansion phase. The FDA has published it's dose optimization guidance document, and dose optimization toolkit for sponsors to reference. 

Question:

1. Is there an out-sized risk of having a question in the Pre-IND meeting related to our dose optimization strategy? We are concerned about going down a rabbit-hole and saddling ourselves with dose-optimization steps early in Phase 1 if we raise the concept with FDA in our Ph 1 design, prior to reaching a POC. Specifically, for molecularly targeted agents that are highly selective, and have moderate-low Grade AEs, but a strong ORR/response rate FDA may be more flexible on "dose optimization" requirements. We know many small biotech's have the same dillemma. I don't believe this is a black-and-white issue to discuss with FDA early. This is more complex. 

Thanks in advance for everyone's input. 

Hello RAPS Community,

We are in the process of filing our first IND, and are planning for a Pre-IND. In our Phase 1 FIH study design for a molecularly targeted small molecule we plan to add a dose optimization cohort in dose escalation that is tumor agnostic but will likely compare 2 therapeutic doses, with the goal of identifying the recommended dose for the expansion phase. The FDA has published it's dose optimization guidance document, and dose optimization toolkit for sponsors to reference. 

Question:

1. Is there an out-sized risk of having a question in the Pre-IND meeting related to our dose optimization strategy? We are concerned about going down a rabbit-hole and saddling ourselves with dose-optimization steps early in Phase 1 if we raise the concept with FDA in our Ph 1 design, prior to reaching a POC. Specifically, for molecularly targeted agents that are highly selective, and have moderate-low Grade AEs, but a strong ORR/response rate FDA may be more flexible on "dose optimization" requirements. We know many small biotech's have the same dillemma. I don't believe this is a black-and-white issue to discuss with FDA early. This is more complex. 

Thanks in advance for everyone's input. 

Hello RAPS Community,

We are in the process of filing our first IND, and are planning for a Pre-IND. In our Phase 1 FIH study design for a molecularly targeted small molecule we plan to add a dose optimization cohort in dose escalation that is tumor agnostic but will likely compare 2 therapeutic doses, with the goal of identifying the recommended dose for the expansion phase. The FDA has published it's dose optimization guidance document, and dose optimization toolkit for sponsors to reference. 

Question:

1. Is there an out-sized risk of having a question in the Pre-IND meeting related to our dose optimization strategy? We are concerned about going down a rabbit-hole and saddling ourselves with dose-optimization steps early in Phase 1 if we raise the concept with FDA in our Ph 1 design, prior to reaching a POC. Specifically, for molecularly targeted agents that are highly selective, and have moderate-low Grade AEs, but a strong ORR/response rate FDA may be more flexible on "dose optimization" requirements. We know many small biotech's have the same dillemma. I don't believe this is a black-and-white issue to discuss with FDA early. This is more complex. 

Thanks in advance for everyone's input.