Scott Koenig: Well, I mean, clearly, the historical data on checkpoints in — first of all, in prostate in general or prostate, certainly, in that line of setting, has been dismal. If you look at all the studies that had been conducted with pembrolizumab, including KEYLYNK-010, KEYNOTE-921, 991 and 641, they all did not meet the expected outcomes, even though those are in different lines of therapy and different combinations. And as you know, from the recent data on CheckMate 650 with a combination of nivolumab and ipilimumab, the responses at nivolumab 3 Ipi 1 were not good with 9.3% overall response rate in the PSA-50 of 13.8%. So we think that we have an unusual molecule now as a bispecific to introduce a checkpoint molecule on top of standard therapy that could really change the course of this disease.
Operator: Our next question comes from the line of with Yigal Nochomovitz with Citi.
Ash Mubarak: This is Ash Mubarak on for Yigal. Maybe just asking another one on lorigerlimab. I think in the past you’ve alluded to the idea of lowering lorigerlimab dose as a way to better manage AEs, but still have full target engagement. And I guess within that context, how are you thinking about dosing for the docetaxel cohort, combo cohort you’re planning on starting up very shortly, are there any specific comments you can make on lorigerlimab dose in that combo?
Scott Koenig: And as you’ve noted, we have a very robust data set from our dose escalation and expansion studies where in our dose escalation we went up to 10 mgs/kg without dose limiting toxicity. Designed the study on expansion at 6 mgs/kg on a Q3 weekly basis in over — in 127 patients, which we presented recently at the ASCO-GU Meeting. As we have pointed out previously, we get full occupancy of PD-1 receptor at 1 mg/kg or higher and have historically shown in a dose escalation study of lorligerlimab, objective response is a 3 mgs/kg and also at 6 mgs/kg. And we were seeing biomarker data of expansion, both CD4s and CD8s at 1 mg/kg or higher, as well as the induction of ICOS in CD4 positive cells in similar ranges. So we have a very wide window of opportunity to adjust treatment doses based on either combinations of drugs that may add on additional toxicities.
So back to your initial question, we are starting at 6 mgs/kg on a Q3 weekly basis. We have the opportunity to make adjustments and we’re also looking at potential future studies where we would study more than the 6 mgs/kg dose in prostate cancer or potentially other tumors as well to get the best safety and efficacy profile for the drugs.
Ash Mubarak: And if I could ask one more on vobra duo. I guess, we’re still waiting for the TAMARACK data before ultimately you make any ultimate decisions. But do you have any updated thoughts on how you’re thinking about vobra duo as a monotherapy within prostate cancer? I think, maybe once we have clarity on the treatment paradigm maybe within the coming years, have you — is there a possibility you would reconsider a pivotal trial with just the monotherapy?
Scott Koenig: Absolutely. I mean, I think the current plan right now was just taking the realization of the time to enrollment where we made the amendments to the protocol of TAMARACK to remove the control group. The idea of this study right now is to execute as quickly as possible, so we were able to decide both on the safety and the activity what is the appropriate dose either the 2 mgs/kg Q4 or the 2.7 mgs/kg Q4. At that point, we would go into — our plan would be, if we achieve the goals that we set for that study, to go into a single arm study moving forward in Phase 3. And clearly, obviously, we’re exploring the opportunity of combining it with other active agents given as was discussed earlier, the combination with lorigerlimab but we’re also looking at other combinations potentially in the future.
Operator: Our next question comes on the line of Kaveri Pohlman with BTIG.
