Nil Navarro-Gorro: Thank you, Tanya. Lovely to be here and being able to discuss these amazing results.
Tanya Dorff: Yes. Your abstract on obrixtamig, a DLL3/CD3 bispecific, caught my eye, for sure. Very interesting. And I guess the first question is, we've seen DLL3-targeted therapy in neuroendocrine prostate cancer with some other agents, so how is obrixtamig different than tarlatamab?
Nil Navarro-Gorro: So besides a slightly longer half-life, probably, with the obrixtamig compared to tarlatamab, I think what caught my eye is the design of the trials. With the obrixtamig treatment it was more focused in a biomarker-selected population.
Tanya Dorff: Oh, well, that makes sense. Following on the results that we saw when Rahul Aggarwal presented a couple of years ago, it seemed like if you didn't have DLL3 target, you just didn't have as much likelihood to benefit. So how did you determine whether patients had the DLL3 expression?
Nil Navarro-Gorro: So patients, to be enrolled in our phase I trial, had to have at least some grade of DLL3 expression, meaning moderate to a strong intensity in immunohistochemistry staining.
Tanya Dorff: And was that done centrally or locally?
Nil Navarro-Gorro: That was done centrally, yes.
Tanya Dorff: So they had to have 2+ or 3+ sort of a thing?
Nil Navarro-Gorro: Exactly.
Tanya Dorff: Or was there an H-score?
Nil Navarro-Gorro: It was 2+ or 3+ immunohistochemistry staining.
Tanya Dorff: And tell me a little bit more about the patients. Neuroendocrine prostate cancer is a little bit of a broad term that can encompass some heterogeneity, so what kinds of treatments had these patients been on previously and what was their kind of presentation?
Nil Navarro-Gorro: So in our genitourinary cohort, we had some patients with prostate cancer, some patients also with bladder cancer. Specifically in the prostate cancer, they could be de novo neuroendocrine prostate cancer or they could also have transformed from previous adenocarcinoma. And mostly had one prior line of treatment, including a carboplatin scheme. But about 70% of the patients had between two or more previous treatments.
Tanya Dorff: So most had had platinum therapy. Were most of them on ADT?
Nil Navarro-Gorro: Yes. In the prostate cancer subgroup, most still had ADT treatment. Yeah.
Tanya Dorff: And so you're reporting, at this meeting, primarily on 10 neuroendocrine prostate cancer patients, is that right? Or did you also show some data on the bladder?
Nil Navarro-Gorro: We showed data from 9 prostate cancer patients, 8 bladder cancer patients, and also 3 gyne patients that were included in this poster.
Tanya Dorff: Okay, great. And so let's get to the results. What kinds of responses did you see with this agent?
Nil Navarro-Gorro: So we saw about a 30% objective response rate with obrixtamig in this specific population and with some higher disease control rates. And what's interesting is that the responses were enriched in those patients that had DLL3-high expression, which meant more than 50% moderate to strong staining by immunohistochemistry. In this population of patients, the signals of efficacy were stronger and the disease control rate went up to 75%, with 50% objective response rates, which I think is pretty amazing in this specific population.
Tanya Dorff: Yeah, that's very striking. What about the dosing? Is this a weekly infusion? Was there step-up dosing?
Nil Navarro-Gorro: So in this trial, there were several dosing regimens. In the poster were included two dosing regimens, which achieved the active dose range between 90 micrograms to 1,080 micrograms, and mostly had a step-up dosing schedule with a dose every week for 3 to 6 weeks, and then every 3 weeks with a target dose.
Tanya Dorff: Great. And what about the toxicity? Did you see cytokine release?
Nil Navarro-Gorro: Yeah, about 60-70% of the patients experienced some grade of cytokine release syndrome, but mostly were low-grade, one cytokine release syndrome grade 1 or 2, and there are no Grade-3-or-higher toxicities associated with cytokine release syndrome. And then we saw some neurological toxicities, which were a little bit higher in those patients with higher DLL3 expression.
Tanya Dorff: Oh, that's interesting. Were you dosing this all outpatient or did you have some inpatient or observation time?
Nil Navarro-Gorro: Yeah, most patients required to be admitted during the step-up dosing, but then they could be treated in outpatient care manner.
Tanya Dorff: Were you using dexamethasone premedication?
Nil Navarro-Gorro: Yes. Dexamethasone was administered during 2 to 3 days after the doses, especially in the step-up dosing procedure.
Tanya Dorff: Yeah. So overall, what was your impression of the toxicity relative to maybe some other agents in this class?
Nil Navarro-Gorro: I think it was pretty similar. It was low-grade and manageable.
Tanya Dorff: Great. So sounds like a reasonable amount of efficacy for acceptable toxicity.
Nil Navarro-Gorro: Yes.
Tanya Dorff: Certainly this is an unmet need. This is a population of patients who do poorly. They don't have a lot of options. So it's great to see this DLL3/CD3 bispecific engager moving forward. And is the study ongoing? Will there be more patients accrued?
Nil Navarro-Gorro: The study is ongoing, but now there's also a phase II trial recruiting patients with small-cell lung cancer, large-cell, and neuroendocrine carcinomas of the lung, and specifically in extrapulmonary neuroendocrine carcinomas, they had to have at least 50% or more DLL3 expression. They are targeting this biomarker-selected population.
Tanya Dorff: Great. Well, we'll look forward to hearing more results in the future. Thank you so much for sharing with us today.
Nil Navarro-Gorro: Thank you very much for having me.