This was a study of ZL-1310 or Zoci. This is a DLL3-directed antibody-drug conjugate and we presented results from the phase Ib portion of an ongoing phase Ib/II study of this drug in extrapulmonary neuroendocrine carcinomas, so including neuroendocrine carcinomas of the GI system as well as other neuroendocrine primaries, including genitourinary, gynaecologic and other neuroendocrine carcinomas.

What was the study design?

This was a phase Ib design where we evaluated the drug in two cohorts – cohort 1 was for patients with gastroentero pancreatic neuroendocrine carcinomas, or GEP-NECs, and cohort 2 was for patients with other extrapulmonary neuroendocrine carcinomas. These include neuroendocrine carcinomas of the genitourinary, gynaecologic system as well as other primary cancers including Merkel cell carcinoma. So these were studied in two independent phase Ib cohorts and we reported preliminary investigator-assessed response rates for each cohort at AACR. We have moved into phase II of the study which the results have not been reported yet.

What were the results of this study?

This was a study looking primarily at overall response rate for patients treated in the phase Ib portion of the study. So all patients had previously been treated with platinum-based chemotherapy and so the expected response rates for standard later-line chemotherapy in this population would be expected to be around 10-15%.

With that context, the overall response rate for patients treated on the study by investigator-associated assessment to date has been 38%. These included 33% overall in the GI NEC cohort, cohort 1, and 44% overall in the other NEC cohort, cohort 2. 

We also evaluated preliminary safety and tolerability of the drug in these populations. We see a relatively low rate of grade 3 or higher treatment-emergent AEs, most commonly cytopenias and nausea. Importantly, we saw a very low rate of drug-associated interstitial lung disease, or ILD, with only one patient in 46 having a grade 2 ILD event.

So we are encouraged by this preliminary efficacy signal and now we are looking forward to evaluating durability of response to drug, both in this trial as well as the ongoing phase II trial which will include neuroendocrine carcinomas of the GI system as well as the bladder, uterus, cervix and large cell NEC of the lung.

What is the importance of these results?

Absolutely. As you know, patients with extrapulmonary neuroendocrine carcinomas can often benefit to a moderate degree from front-line platinum-based chemotherapy. But after progression of their disease on front-line platinum-based chemotherapy we have very, very limited options and we generally treat with chemotherapies but generally it’s associated with lower response rate and short duration of response.

So we have a major need for new therapies in this patient population and we are excited about the initial response signals seen so far for this DLL3 ADC in this patient population. We hope to show that many of these responses can be durable and so we are looking forward to evaluating the activity of this drug in larger cohorts.

We also think that this could be just a first step as a proof of principle that a DLL3 ADC can have activity in this population. We also do think this could also be a platform for combination with other therapies, other DLL3-targeted therapies or even other non-DLL3 targeted therapies, given the good safety and tolerability we have demonstrated with this drug so far.