So I think the consultations that are ongoing with those constituencies will ultimately decide what is good enough, and then we’ll be able to benchmark our actual data against that and decide if that’s a meaningful important improvement and decide what to go forward and how.
Jonathan Chang: Understood. Thanks for taking my questions.
Operator: And one moment for our next question. And our next question will come from Chris Shabutani of Goldman Sachs. Your line is open.
Unidentified Analyst: Hi, good morning. This is Charlie on for Chris. Thank you so much for taking our questions. Just to start, wondering if you could provide some clarity on the 6236-6291 combination trial that’s enrolling. Who are you actively recruiting in terms of G12C experience versus naive patients in that study? And then my second question is just regarding the potential for tissue agnostic approval. What does the team see as the clinical bar to reach there in terms of ORR? Thank you.
Mark Goldsmith : Just a clarification on your second question, Charlie. Were you asking about for the combination or for either of those compounds individually or just more generically?
Unidentified Analyst: I guess more generically.
Steve Kelsey : The 6236-6291 combination protocol right now is enrolling both lung cancer and colorectal cancer patients. And the colorectal cancer cohort will prioritize patients who have not had a G12C inhibitor. The lung cancer cohort right now allows either. And we’re not at the point where we’re biasing in any one direction or the other right now because we’re still in the dose escalation, dose finding, dose exploration mode, and it doesn’t really matter frankly, what disease or prior treatment the patient has for that purpose. So as soon as we’ve got a dose for that combo, then I think we’ll be a little bit more selective about the patients that we want to encourage into the study, and that will, to some extent, depend on what we’ve seen during the first escalation period.
I think everybody knows accelerated approval, getting a little bit harder. The glass is coming off at a little bit. The bar moves around depending on the indication, frankly. But accelerated approvals traditionally have been given for single agents with response rates in the sort of 25% to 30% range. And I don’t expect it to be any different for a RAS inhibitor and RAS mutant disease, particularly as the precedent that has essentially been set by the accelerated approvals of sotorasib and adagrasib.
Mark Goldsmith : He was asking specifically about the tissue-agnostic, tumor-agnostic strategy.
Steve Kelsey : Yeah. I think — no — but I think the — in the core indication — if you pursue a tissue-agnostic strategy, there’s going to be a couple of indications that are going to dominate that cohort. And I think the response rate has to be in that sort of 30% range, I think, in order for anyone to take that seriously. Clearly, the point of the tissue-agnostic strategy is there are going to be some indications which are so uncommon. There’s only going to be a handful of patients and you won’t be able to compute a response rate with any degree of certainty. So we’re really talking about the confidence intels around the overall response rate to lead indications within that cohort.
Unidentified Analyst: Yeah. That’s very helpful. Thank you all very much.
Operator: And we do have time for two more questions. One moment for our next question. It will be coming from Ami Fadia of Needham.
Ami Fadia : Good evening. Thanks for taking my questions. With regards to the pivotal trial, you’re planning in lung, do you believe that you need to generate data in G12C patients before you begin the trial and perhaps give us a sense of the number of patients you think you need to enroll for this type of invested trial design? Thank you.
Mark Goldsmith : Thanks, Ami. I think Steve can comment on that.
Steve Kelsey : I didn’t quite understand the first part of your question is?
Mark Goldsmith : Do we need to validate G12C in humans before –?
