Pivotal AIM-HN Clinical Trial of Tipifarnib in HNSCC

Glenn J. Hanna, MD: We can talk a bit about the follow-up study, you alluded to it. It branched out of the initial trial, and this is the pivotal trial, the so-called AIM-HN [head and neck] or TIP-007 trial. Do you want to talk about how that trial involves or differs from the parent study?

Nabil F. Saba, MD, FACP: The new study, as you mentioned, looks deeper into the molecular alterations of the HRAS alterations in head and neck cancer, so it looks at mutations but looks also at VAF [variant allele frequency]. I think that will give us better answers because if you look at the data from the first study, these patients, as you rightfully mentioned, do seem to benefit depending on the frequency of this alteration. The new study will be basically digging deeper into looking at these subgroups of patients to see whether the approval or the use of tipifarnib should be in all of these patients versus a certain group of patients. If you look at the responders in the first study, all of them had alterations, and all of them had a VAF that exceeded the threshold I believe of 30%. This is an indication that the type of test that we get matters for future prediction of clinical activity.

It will be a larger study, a definitive study, as you said. It will look deeper also into the tolerance of the treatment, the clinical activity of the treatment, and it’s focused on head and neck cancer, given the responses we’ve seen in the first trial. I think the very interesting aspect you also mentioned is that interaction with EGFR and the PI3 kinase. There is clearly an interaction between the HRAS and these. These tumors appear to not be having TP53 alterations when you look at the genomic characteristics; these tumors appear to be somewhat excluding patients with TP53. So, there’s something we need to learn about the biology, how to dig deeper into identifying a subset of patients with head and neck cancer who should be targeted differently. The interesting part also is it seems to be cutting across the HPV [human papillomavirus]-positive and negative, more so HPV-negative group. We look forward to of course seeing results and to improving accrual and getting an FDA approval. I think the FDA priority status of tipifarnib is a good indication that even if you have a small study, that is making a difference for patients who have otherwise very few options of care. Certainly, that is a path to approval, and it is really nice to see that.

Glenn J. Hanna, MD: I thought it was interesting that with the companion piece to the study, the so-called AIM component with the active drug for patients with HRAS mutations, they’re also looking at this HRAS wild-type, the SEQ component of the trial, the SEQ-HN part, which is another few hundred patients. They’re collecting disease history and first-line outcome data to prospectively match with the HRAS-mutated folks to compare response rates and trajectory. I think that’s meaningful. It’s always great to see a molecularly targeted agent deliver a response rate and durability for a small group of patients, but it’s also valuable to see how that compares to patients who are on our other standard options more generally, like immunotherapy or in the platinum-refractory setting. I thought that was an interesting component of the design, that they’re doing a matched, sort of synchronous or analogous study in the HRAS wild-type folks.

Transcript Edited for Clarity