Hendrik-Tobias Arkenau, MD, PhD, discusses the phase I JAVELIN trial as well as the future of treatments and immunotherapies in the treatment paradigm of gastrointestinal cancers.
Hendrik-Tobias Arkenau, MD, PhD
Despite only being tested in a phase I trial, Hendrik-Tobias Arkenau, MD, PhD, believes that avelumab holds promise in patients with advanced gastric or gastroesophageal junction cancer.
In an interview withTargeted Oncology, Dr. Arkenau, executive medical director of the Sarah Cannon Research Institute UK, and the clinical lead for the Hospital Corporation of America International Cancer Service Line, discusses the phase I JAVELIN trial, which enrolled 1600 patients with various solid tumor types to receive avelumab, as well as the future of treatments and immunotherapies in the treatment paradigm of gastrointestinal (GI) cancers.
TARGETED ONCOLOGY:What can you tell us about the JAVELIN trial?
The phase I JAVELIN trial is the largest phase I clinical trial of a PD-L1 inhibitor right now, with 1600 patients enrolled. We recently presented the safety and efficacy data. In terms of safety, this trial confirms that the adverse events are in line with previously reported side effects, especially from immunotherapies, which include hepatitis and other immune-related effects. There were no real outliers, so avelumab is safe to give in this really large patient population.
Particularly of interest is a subgroup of patients in an expanded cohort of gastro-esophageal patients and patients who progressed on the first line in standard therapy, and benefitted. Again, in this cohort, there were no significant side effects, and what we're reporting is that some of these patients have increased benefit in terms of progression-free survival. Overall, this is really interesting data to bring forward into randomized clinical trials in the later stages.
Of particular interest is not only the avelumab data, but also recent data on immunotherapy mismatch repair-deficient GI cancers, particularly colorectal cancers. Here we see really exciting and promising data, and these colorectal cancer patients don't normally respond to standard chemotherapies, progressing very quickly. The data we now see from KEYNOTE 16 is that patients with mismatch repair colorectal cancers had a response rate in the range of 60%, disease control rate of about 40%, and a 2-year progression-free survival and overall survival rate of 61% and 66%, respectively.
These are really exciting results, perhaps most importantly was that the toxicity profile for patients was really good and was managed well. That's really what I see as the most exciting part in the GI arena.
TARGETED ONCOLOGY:Immunotherapies are certain to generate a lot of excitement within GI cancers. What are some exciting advancements on the horizon?
In terms of advancement with immunotherapies, it is certainly immune combinations. To enhance the effect of the CTA4 or PD-1 and PD-L1 blockage, you can combine those inhibitors, and that's really exciting. Certainly one of the data recently presented at ASCO was the management of checkpoint blockage, but also manipulation of T cells in such a way that you have some stimulatory effects like OX40 combinations where we've seen some very interesting data.
I've seen data specifically where there will be OX40 PD-1 combinations with no added toxicities, so when there are more phase II and expanded cohorts, we will be very interested to see these data from a safety point of view and an efficacy point of view as well.
TARGETED ONCOLOGY:Can you tell us a little bit about nivolumab plus ipilimumab in colorectal cancer?
Combinations of immunotherapies in colorectal cancer are of interest right now, but the strongest significance is in the mismatch repair gene in colon cancer populations. However, for the biology part of things, we see that CTLA4 inhibition can actually add to PD-L1 tumors we've seen in melanoma and lung cancer. So combining a CTLA4 inhibitor, probably at a lower dose than we usually use in standard therapies, may increase PD-L1 expression in tumors and therefor allow either PD-1 or PD-L1 inhibitors to add benefit in the colorectal populations.
TARGETED ONCOLOGY:What are some of the biggest challenges in treating patients with GI cancers?
Patients with gastrointestinal cancer are often very heterogeneous, so upper GI cancers, pancreatic cancers, things like that where we haven't seen the greatest benefits of immune therapies right now is certainly the biggest challenge for us. We have some very early data in some GI cancers, but I think it's too early to assume that some immune therapies are standard of care.
For gastric cancers though, the biggest challenge for us right now is to get the window of opportunity right. So you know, getting the patient once they've progressed on their standard-of-care chemotherapies onto clinical trials quickly and efficiently with relevant biopsies and biomarker data. These patients are often challenging to treat because they progress very quickly, cause lots of weight loss, have lots of obstructions, and so on and so forth. If we see these tumor types benefitting from these treatments then that would be really great.