Chinese Cancer Drug Set to Transform Global Market: Glecirasib | Most Promising Cancer Drugs 2024

In this exclusive interview with Dr. Andrea Wang-Gillam, we discuss the revolutionary potential of Glecirasib and its possible impact on cancer treatment worldwide.

Andrea Wang-Gillam, is a chief medical officer at Jacobio (US) Pharmaceuticals, Incorporated and an Associate Professor at Washington University. She completed her education from University of Arkansas for Medical Sciences, College of Medicine.

Dr. Amalya Sargsyan is a Medical Oncologist at Yeolyan Center,  a Research Physician at the Immune Oncology Research Institute, and Senior Editor at Oncodaily. She holds an MD from Yerevan State Medical University and an MSc in Precision Medicine from the University of Cyprus. 

00:00 Chinese Cancer Drug Set to Transform Global Market: Glecirasib | Most Promising Cancer Drugs 2024
01:24 Introduction
02:38 Overview of Glecirasib
03:26 Up-to-date results on clinical trials
05:13 Other indications of Glecirasib
06:09 Safety profile
07:54 How to focus research area
09:35 The most promising application of Glecirasib
10:50 FDA approval stage
12:19 The biggest challenges faced
14:35 What to expect next

Amalya Sargsyan: Hello everyone and welcome to Onco Daily where we will discuss the 10 most promising cancer drugs not yet approved in solid tumors 2024 edition and today we’re going to focus on one of the most groundbreaking drugs, Glecirasib.

I’m Amalya Sargsyan, a medical oncologist and the senior editor at OncoDaily and today we have the pleasure of welcoming Dr. Andrea Wang-Gillam, who is the chief medical officer of Jacobio Pharma and also she is in charge of global clinical development and operations at Jacobio Pharma project. Welcome Dr. Andrea Wang-Gillam and thank you for your time being with us today. Glad to be here. ,Can you please briefly introduce yourself and your background?

Andrea Wang-Gillam: Sure, my name is Andrea Wang-Gillam, a medical oncologist by training, have been practicing oncology particularly in phase one setting as well as GI oncology settings over the last 15 years or so. Prior to joining Jacobio as CMO, I have been practicing oncology at an academic institution for a long time.

Amalya Sargsyan: Thank you, that’s very remarkable. And just starting about discussing our drug, can you please provide an overview? What is Glecirasib?

What does it do? What are the main indications?

Andrea Wang-Gillam: Yeah, so Glecirasib is one of the KRAS-D12C small molecule oral inhibitor. It is very potent covalent inhibitor, GDP KRAS. So this is a drug that has been developed at years at Jacobio.

We have completed our pivotal phase two study, single arm phase two study in non-small cell lung cancer in patients who have progressed in standard frontline therapy.

Amalya Sargsyan: Yes, congratulations on your presentation at ASCO. I had the privilege of attending there. You’re presenting the results.

Can you please update with the most up-to-date results on the trials which were already completed?

Andrea Wang-Gillam: Sure, sure. Yeah, so the presenter was one of the leading PIs, Dr. Shiyuan Kai, last name is Dr. Xu. He has initially presented our pivotal data at ASCO Plenary Study on April 30, 2024.

That was well received and it was also part of the panel discussions at that time. And then the data was updated at ASCO rapid, part of the CME for all the presenters was rapid. So it’s kind of rapid translation.

And that is part of the collection of the abstracts that has been presented at ASCO Plenary Study. So our study has enrolled 119 patients with non-small cell lung cancer harboring KRAS G12C in the second line settings above. 94.1% received a standard platen-based therapy plus IO therapy. What we observed, the primary endpoint is actually confirmed OR by IRC. And our data show to confirm OR are 47.9%. Therefore, patient actually had a CR. The median PFS, 8.2 months. So I think that’s very encouraging compared to the existing FDA-approved drug.

Amalya Sargsyan: That’s very encouraging and glad to hear that in this population, we are achieving this kind of results. And are there any other indications where GLAG recipes being tested for?

Andrea Wang-Gillam: Yeah, sure. Because it’s such a potent drug, we have tested in pancreas cancer and other rare disease type and also CRC, colorectal cancer with KRAS mutant, KRAS G12C mutant. And those data has been reported different medical conference.

So for instance, our KRAS G12C data, single agent data has been reported at a GIS, so as our presentation shows really promising results. So I think because of that, we have initiated pivotal trials in pancreas cancer in China, and then hopefully that will expand to the outside of China.

Amalya Sargsyan: Oh, that’s encouraging. Hopefully we get the results soon. And what would you tell us about the safety profile of the drug?

Andrea Wang-Gillam: Yeah. So see, the drug is well-tolerated. I think one of the key thing is that GI toxicity are very minimal.

So I think a key thing when you think about KRAS G12C is the existing drugs, AE profiles, largely lie into GI toxicity. It’s part of both sort of aggressive, I think aggressive more predominantly. Our drug has a minimum GI toxicity.

For instance, diarrhea, nausea, vomiting, all less than 10%. Nearly no grade three treatment related to nausea, vomiting, diarrhea. So I think that is really helpful for patients who gone through extensive treatment in the past, for instance, frontline therapy, they now have a lot of nausea, vomiting, underlying issues.

So I think that this drug can make them more compliant with our administration and the minimum GI toxicity. I think that’s one part I think that stand out, differentiate us from other treatments.

Amalya Sargsyan: So you say that the safety profile is improved with the drug that we have on the other markets. That’s very remarkable. And indeed for patients, it’s one of the most important thing also, the quality of life.

And so having led more than 60 clinical trials and developing the trials that were led to FDA approval and changing the treatment landscape. So how do you see where to focus your research area? What are your secrets?

Andrea Wang-Gillam: Yeah. So I think that part of it, this is a really evolving landscape is extremely exciting for people who have done RAS research in the past. For me, has been oncologists who have done a lot of clinical trial targeting various part of the RAS pathway.

So I think it’s very encouraging with the sort of emerging class of drug with a direct inhibitor and also some of the pan-RAS inhibitor that’s currently in clinical trial. So I think that for us at JicoBio, we also have a SHIP2 inhibitor. So our focus is in combination of KRAS G12C plus our SHIP2 inhibitor because a SHIP2 inhibitor in a preclinical setting had demonstrated synergistic anti-tumor effect in particular non-small cell lung cancer KRAS G12C model.

So we have sort of a really good sample size, about a hundred patients who actually were treated with a combo of non-small cell lung cancer in a frontline setting with promising efficacy. So that’s part of a company’s strategy in terms of how we bring KRAS G12C forward in a frontline setting, it’s in combination with our SHIP2 inhibitor. And by the way, that was also presented as well as oral presentation.

Amalya Sargsyan: In the developmental therapeutic session, right? Yes, yeah. Yeah, but I did that.

It was very encouraging and very nice to hear this most promising drugs. And as a PI and leading JicoBio pharma, where do you see the most promising application for electrophysiology in cancer treatment? 

Andrea Wang-Gillam: Yeah, I think what we really like to see is because we have launched our phase three trials, the registration trials with SHIP2 plus KRAS G12C in the frontline non-small cell lung cancer. So this has improved by CDE. They were also hoping to bring this combination outside of China.

So I think I’m really hoping to see actually a benefit of two oral drugs in the frontline non-small cell lung cancer. I think that would be extremely helpful for patients that don’t have to go to the hospital taking IV medications by just taking two oral medications. So I think that is something we’ll focus on for the future development of KRAS G12C.

In addition, obvious single agent pancreas and perhaps the CRC, but I think the main focus for us sort of medium-sized biotech is the frontline combo study.

Amalya Sargsyan: Yes, indeed. You have a really nice point of saying oral drugs, people staying at home and also giving potency, it will be really beneficial and hopefully in frontline study we’re going to get these good results. So in which stage of FDA approval is the drug now and what are your prognosis regarding this process?

Andrea Wang-Gillam: Yeah, so I think that you were asking regarding, so this drug actually is being submitted to the NDA in China. So that’s being reviewed as we speak. So we are, you know, we’re looking forward to get a feedback from China, you know, CD or NMPA.

And meantime, we have done single agent studies in US, extra, you know, in Europe. So, and also we’re done combo single agent for SHIP2 and both KRAS G12C in extra China. So we’re really hoping to soon be communicating with FDA and EMA regarding our China data and you’ll see where we’re going with the pivotal trial design.

When are we going to expect the results of the pivotal trials? We’re hoping to, pivotal trials require large sample size, you know, randomizations. So we’re hoping complete enrollment by end of the next year in China.

So that is, that’s, you know, a projection. And then we should be seeing, you know, clinical data soon after that. 

Amalya Sargsyan: We look forward to the results and hopefully we can see the good results there and bring the hope for our patients. And while we’re doing all this research, we have a lot of challenges in our way. What were the biggest challenges you have faced in your research and what did you do and how do you overcome?

Andrea Wang-Gillam: Yeah, I think in terms of research or global development, you know, this DracoBio is large, based in China, but have a U.S. R&D side. So I think for us, we really hope to utilize the part of China data with safety data extra China and also move the sort of, move the trial or expand the patient population outside of China. So for us with the current, you know, a competitive landscape.

So we really need to have a differentiation approach in terms of how to tackle KRG12C patients with non-small cell lung cancers globally. So that’s why we positioned ourselves, you know, slightly different from the larger pharma with the oral-oral combination. Additionally, I think, you know, we need to also be mindful of the cost of the studies, of the clinical trials.

And also when we move the trial outside of China, we need to be mindful of a truly global trial with diversity patient population that would more reflect whatever the region we’re doing the trials in. So I think all those things, you know, need to be taken consideration for global clinical trial design. Yes, it’s very important.

Amalya Sargsyan: And these challenges for foreign companies facing to globalization of their research and bringing it to bigger market is a problem. Hopefully we’re overcoming it. And I see you already have the expansion cohort of another population too.

Hopefully it goes bigger and bigger. And as we are going to summarize, and thank you for sharing your research. Is there anything else you would like to share about like RACIP and what to expect next?

Andrea Wang-Gillam: Yeah, we really hope that, you know, we’re, you know, next a few milestones. One is receive the NMP approval, you know, in China, and also aligned with FDA and EMA regarding our pivotal trial with our combinations of frontline non-small cell lung cancer. And also get a readout with our pivotal trial in pancreas cancer.

So I think in summary, we’re really hoping to expand sort of our trials territory outside of China and, you know, and also looking for collaborators that expedite drug development extra China.

Amalya Sargsyan: It’s very encouraging. Thank you, Dr. Wang for being here today and for joining us for this discussion. We’re very excited to the results and hopefully we can see the bigger results soon.

And congratulations on already presented results at ASCO. And your work is truly inspiring and brings hope, not for us, for our patients too. Thank you for joining us today at Oncodaily.

We are very happy that we have featured the Glecirasib as one of the most promising cancer drugs, and hopefully we’re going to get approval very soon. Until then, we wish you continued success and the work you are doing is very important. Thank you for being here.

Andrea Wang-Gillam: Thank you very much. Appreciate that. Thank you.