AstraZeneca Head of Immuno-Oncology and Gastrointestinal Tumors Franchise Discusses Key Phase III Trial Results in Hepatocellular Carcinoma

ACT: AstraZeneca recently announced positive results from its Phase 3 trial in patients with hepatocellular carcinoma (HCC) who are eligible for embolization at ASCO GI. For our viewers, can you provide us with a brief description of what the data showed?

Goel: This is exciting in that it was the first study ever to show positive results for systemic therapy in combination with transarterial chemo embolization in this setting. We also had additional data with secondary endpoints such as TTP or trying to progression with a median TTP of 22 months versus 10 months. All our study endpoints that were mature enough at this point were met. The study will continue to assess a key secondary endpoint of overall survival.

ACT: What implications do you think these results will have for HCC patients going forward?

Goel: Rates of disease progression have remained high following embolization treatment. Many patients who receive embolization actually experience disease progression or recurrence within eight months. If approved, this would not only be the first systemic therapy to show benefit for these patients in what we call the intermediate setting, but could also transform care as a whole by affirming the MDT approach or multidisciplinary care approach for liver cancer patients. Liver cancer is a pretty complex disease. A physician not only has to treat the tumor, but also take care of overall liver health. So, an integrated MDT approach is a really good thing for patients.

ACT: How else is AstraZeneca doubling down on developing novel treatments for patients with earlier-stage GI cancers?

Goel: At AstraZeneca, we believe if we can intervene earlier, we have a better chance of improving long term outcomes for patients. In GI cancer specifically, we have an extensive clinical development program further assessing across earliest stages of disease.

I'll start with complementary studies to the EMERALD-1 study in the ambulatory embolization eligible HCC population. We have a study, EMERALD-3, which is in combination with IMJUDO and levantanib, as well as with bevacizumab, bevacizumab, or bev following TARE which is another form of embolization treatment called transarterial radioembolization in unresectable, HCC. We hope that across these three studies, we will be able to provide HCPs and patients with a variety of options that best support the individual patient with intermediate disease as HCC is so heterogeneous.

Continuing with HCC, we also have another study in earlier settings with with EMERALD-2 that's in the adjuvant HCC space, so after surgery. This is also in combination with bev.

Lastly and not least, moving on to gastric cancer, we have the MATTERHORN study and resectable, gastric and gastro esophageal junction cancers. In this study, IMFINZI is being studied before and after surgery in combination with chemotherapy, and we saw the initial readout in terms of response rates also presented at ASCO GI.

While not specifically early disease, IMFINZI is also being studied in locally advanced unresectable esophageal cancer with and after chemoradiotherapy and that is known as the KUNLUN study. Importantly, IMFINZI is being accessed with or without IMJUDO across extensive tumors, including esophageal, gastric, long bladder and liver cancers, really spanning early to late disease. So, really quite an extensive program on the IO front here.

ACT: At ASCO GI, you also presented data on the MATTERHORN Phase III trial in patients with resectable, early-stage and locally advanced gastric and gastroesophageal junction (GEJ) cancers. Can you go into more detail about the improvements that were made as a result of this trial?

Goel: For the MATTERHORN study, we first presented early results at ESMO in October of last year. We saw positive results from a planned interim analysis that showed IMFINZI in combination with standard of care chemotherapy known as FLOT, more than doubled the key secondary endpoint of PCR or pathologic complete response versus chemotherapy alone for these patients.

We also then presented late breaking results from the trial at ASCO GI just this January, demonstrating consistent improvement in PCR across countries and regions in the trial with magnitudes similar to those seen in the overall patient population.

This is important because other studies have shown superior outcomes in Asian populations compared to non Asian populations in this setting, even when stratified by stage. In the analysis presented at ASCO GI, PCR improvement was consistent in Asia, Europe, North America and South America.

ACT: Is there anything else in the works regarding AstraZeneca’s oncology pipeline that you would like to mention?

Goel: It's a super exciting time to be at AstraZeneca. We have an interesting and diverse pipeline in oncology spanning multiple modalities, including the next wave of ADCs and by specific immuno-oncology agents. I'm really interested in the bispecifics, because of the promise of the bispecific in maximizing the ability to deliver a therapy targeting two components of the immune system in one therapy.

In late 2022, we launched a novel combination regimen of two of our IO agents. They were IMFINZI , an anti-PD1 agent, and IMJUDO, an anti-CTLA4. Last year, we shared survival data for years in firstline HCC which has been seen for the first time in this setting. I'm excited to see what bispecifics can do to simplify few donations into one therapy. If you have one agent with two modalities on it, we can explore whether we can further enhance combinations, reduce chemotherapy, or the number of infusions a patient needs, with the potential of continuing to improve efficacy.

Lastly, I'll share that at ESMO last year, we presented for the first time our progress on three new IO by specifics, all with the potential to pave the way for the future of IO. I'm really excited to see the continued development of IO agents with the bispecifics and beyond, and I really do think we've only just begun to scratch the surface of what IO can do.