Median overall survival is set to be more than 2 years, which is more than double the overall survival of current frontline therapies.
Xiaolin Zhang, PhD, founder, chairman and CEO of biopharmaceutical company Dizal Pharmaceuticals, China, joins Pharmacy Times at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, taking place December 9-12, 2023, San Diego, California, to discuss significant efficacy results that have emerged from the JACKPOT8 trial, which is evaluating golidocitinib for peripheral T-cell lymphoma (PTCL), an aggressive non-Hodgkin lymphoma (NHL). In this interview, Zhang discusses the need for better therapies, and details new and important data relating to duration of response (DOR) and overall survival (OS) in patients.
PT Staff: What are current treatment options in the PTCL space?
Xiaolin Zhang, PhD: This is a is a very nasty disease, and especially for patients who relapse or refractory from the frontline treatment. And for the front-line treatment, it is basically a cocktail of chemotherapies— very toxic. Once the patient will fail the frontline treatment, the prognosis is dismal.
There is indeed no standard of care (SOC). In the United States, they have chemotherapy and one of the histone deacetylase inhibitors (HDAC) available on the conditional approval In Europe, they're not. In China and some Asian countries, they have another type of HDAC inhibitor. So there's no SOC, which kind of reflects that just there's no clear effective therapies once a patient progresses after first line treatment. And generally, the survival is awful, 6-8 months. So it is a disease really need good therapy, and our patients deserve that.
PT Staff: JACKPOT8 is evaluating Janus kinase 1 (JAK1) inhibitor, golidocitinib, for r/r PTCL. How does a JAK1 inhibitor act on this disease?
Xiaolin Zhang, PhD: This is a fascinating scientific story, actually. Indeed, golidocitinib is one of the only JAK inhibitors in the STAT-led clinical studies for PTCL. What we found is, among over 1000 tumor cell lines (we screened for golidocitinib on a few cell lines and found that they are exquisitely sensitive to golidocitinib). When we looked at it, [asking] why are these tumor cell lines sensitive to golidocitinib, we found they all have this PTCL origin.
So we say, “That's interesting.” Now we did some further extensive studies, including take some of the tumor cells from the patients, and we confirmed that A) the JAK/STAT pathway is super active in many of these patients who are PTCL patients, and B) they are sensitive in both cells and animal models to golidocitinib. This gives us kind of scientific foundation that we test the clinical hypothesis (during preclinical findings and clinically)— that [is], whether golidocitinib (by hitting the JAK/STAT pathway) can bring effective benefit to the PTCL patients. That's how this all started.
PT Staff: Can you describe the JACKPOT8 study? What were study outcomes?
Xiaolin Zhang, PhD: During this year's ASH, and we will report the full study analysis for JACKPOT8, which is a randomized, multicenter and multinational study that is testing golidocitinib [for] safety and efficacy in PTCL patients after they relapse from front end treatment. So, all the patients have progressed after the frontline treatment (most of them are chemotherapy relapse patients). What we observed is confirmed objective response rate (ORR) of close to 45%, which is significantly higher than current agents— all of them are below 30% for the stats and chemotherapies. This is number one. but close to 25% of them are complete response (CR), which is very important for PTCL lymphoma patients. The response(s) are [also] very durable; the duration of response (DOR) is over 20 months and still going. So we don't have a mature median DOR yet. And the patient overall survival (OS) data, while not mature, is close to 2 years now. So the median OS will be over 2 years.
Remember— with fully relapsed and refractory PTCL, the current OS is 6-8 months. So, we are extending from 6 months to over 2 years. The community really views that golidocitinib can bring significant improvement in terms of efficacy and safety for the PTCL patients.
PT Staff: What is the significance of presenting updated data about golidocitinib at ASH 2023?
Xiaolin Zhang, PhD: ASH is one of the most prominent conference for the hematological diseases. This is the first time we are presenting a complete analysis of the study. We have finished the analysis and we have submitted a new drug application (NDA) to regulatory agencies, which is under review. So this is the first time the full results in presented. These result are very much consistent with what we have reported, but this is the first time actually report that DOR, which is very important for the second line treatment, right? You see high responders, but they have to be durable in order for the response to be really meaningful to the patients. We also present the OS, as I just mentioned, that that is still ongoing. It [isn’t] mature yet, but for median OS, we know it's going to be over 2 years. That is a really significant improvement from the current OS of 6-8 months.