The American Society of Clinical Oncology (ASCO) annual meeting happens each June in Chicago. It is one of the premier meetings each year where oncologists, scientists and advocates gather to hear the latest clinical trial data in oncology, including focused sessions on GI cancers such as colorectal cancer (CRC).

The theme this year is “Collective Wisdom: The future of patient-centered care and research.” As the leading CRC advocacy organization focused on research progress, Fight Colorectal Cancer will be there to report on the findings!

Because it’s a scientific meeting, written abstracts (short summaries) of posters and oral presentations were released ahead of the meeting. Thousands of abstracts are published each year. To help you follow the research that will be coming out of ASCO, I went through them with the Fight CRC team and identified some of the talks and posters that we feel are laying the groundwork to potentially impact the lives of colorectal cancer patients.

TOM’S TOP 5 ABSTRACT PICKS

After reading the colorectal cancer abstracts for ASCO 2016, here’s my list of experimental therapeutic abstracts that I felt deserve particular attention as the meeting approaches. These are studies that I believe patients will be particularly interested in – studies that could potentially have near-term clinical significance (within the next five years!) as it relates to your treatment options. This list is not exhaustive.

(Spoiler alert: There’s preliminary signs of potentially significant activity of an immunotherapy combo-therapy in non-MSI-high CRC!)

1. KRAS-mutant, non-MSI-high patients responding to combination immunotherapy

Name: “Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC)”

Abstract Number: Abstract 3502

Overview: As I wrote about previously in my blog on PD-1 and MSI, non-MSI-high CRC has thus far proven resistant toward immunotherapies. Abstract 3502 indicates a potentially significant step forward in addressing this problem.

Previously, when the PD-1 inhibitor pembrolizumab was tested in patients with non-MSI-high CRC, only 10% of patients benefited from the therapy and their tumors did not shrink, they only stabilized in size (“stable disease (SD)”).

In the new trial data disclosed, the therapy studied was a related PD-L1 inhibitor atezolizumab combined with a targeted agent: the MEK inhibitor cobimetinib. Significantly higher activity was seen in the small number (23) of patients tested than had been seen using pembrolizumab monotherapy (using it by itself) in the earlier trial: there were four “partial responses” (PR) (PR = at least 30% reduction in tumor size) and five additional patients achieved stable disease.

Most/all of the patients were both KRAS-mutant and had non-MSI-high CRC (study details indicate one of the patients had an unknown MSI status.)

Further details will be disclosed during the oral presentation on June 5. I’ll be looking for information about how long patients who showed a response continued to do so (i.e. the “durability” of the response), among other factors.

Although this trial was only in a small number of patients and will require confirmation in larger clinical trials, at the scientific level, this study appears to be a significant step forward! It shows for the first time that an immunotherapy checkpoint inhibitor can achieve objective clinical responses in non-MSI-high CRC by using an appropriate combination therapy. There are numerous additional checkpoint inhibitor combination therapies in early phase clinical trials, some of which will hopefully further support this observation with additional clinical responses!

Patients Need to Know:

• Study shows that on a scientific level, certain immunotherapies (checkpoint inhibitors) when combined with other drugs may provide future treatment options for some patients with non-MSI-high tumors.
• Future clinical trials that will attempt to replicate this small study’s findings in a larger group will need participants.
• There are a number of other immunotherapy clinical trials looking at how to combine therapies and help non-MSI-high CRC patients.
• It’s imperative to know your MSI status. Read our fact sheet to get more information.

2. Patients on FOLFIRI therapy respond positively to addition of novel therapeutic drug

Name: “Phase Ib extension study of cancer stemness inhibitor BB608 (Napabucasin) administered in combination with FOLFIRI +/- Bevacizumab (Bev) in patients (pts) with advanced colorectal cancer (CRC)”

Abstract Number: Abstract 3564

Overview:  The novel experimental therapeutic BB608 (Napabucasin, formally BBI-608) showed a very high response rate (disease control rate, i.e. PR + SD of ~90% with most stable disease patients showing some level of tumor regression) when administered in combination with FOLFIRI (on patients who did and did not receive bevacizumab) – even in patients who had previously been resistant to FOLFIRI therapy. Important details I’ll be looking for in the presentation include the level of activity seen in patients who had previously been resistant to FOLFIRI-based therapies.

Patients Need to Know:

• This may impact patients on FOLFIRI therapy (especially those resistant to it) but more research will be needed.

3. mCRC patients show promising preliminary results for a novel immunotherapy

Name: “A phase 2 study of NEO-102 (ensituximab), a novel chimeric monoclonal antibody, in adult patients (pts) with unresectable, metastatic colorectal cancer (mCRC)”

Abstract Number: Abstract 3080

Overview: NEO-102 (ensituximab) is a novel immunotherapy targeting a unique form of the MUC5AC protein identified in a CRC vaccine. In the previous analysis of its Phase 2 trial, it has shown promising preliminary results in terms of both disease stabilization as well as overall survival compared to historical data.

The final results of its Phase 2 trial will be released at ASCO 2016. One important detail I’ll be looking for in the presentation is the durability of response, which means for how long responding patients responded to the therapy.

Patients Need to Know:

• CRC vaccines continue to uncover important details for research. Learn more about them in my past blog post.
• If the therapies move to Phase 3 trial, more patient participants will be needed. Learn more about finding clinical trials.

4. A next-generation EGFR-inhibitor shows promise – even for RAS/RAF mutations

Name: “Final results of a first-in-human study evaluating the safety, pharmacology and initial efficacy of MM-151, an oligoclonal anti-EGFR antibody in patients with refractory solid tumors”

Abstract Number: Abstract 2518

Overview: MM-151 is a next-generation EGFR-inhibitor. The abstract reports that almost half of the CRC patients in the study achieved either PR or SD. Interestingly, this included patients with multiple resistance markers, including RAS/RAF mutations which are normally associated with EGFR-inhibitor resistance.

Important details I’ll be looking for in the presentation include the percentage of responders received MM-151 in combination with FOLFIRI versus being dosed with MM-151 alone, as well as the number of RAS/RAF-mutant responders.

Patients Need to Know:

• EGFR therapies – learn more about them in our skin toxicity video and EGFR page.
• First-in-human study means more trials to come (trials that will need participants).
• Biomarker testing will let you know if you have a RAS/RAF mutation. Download our fact sheet to know more.

5. Potential impact of immunotherapy on heavily pre-treated patients (including non-MSI high)

Name: “Anti-tumor activity of PEGylated human IL-10 (AM0010) in patients with pancreatic or colorectal cancer”

Abstract Number: Abstract 3082

Overview: AM0010 (PEGylated human IL-10) is an immunotherapy that appears to potentially impact both disease stabilization as well as overall survival of heavily pre-treated CRC patients. Data will be released not only on these, but also on the potentially beneficial immune system effects of AM0010, even in immunotherapy-resistant tumor types such as non-MSI high CRC.

Also of Interest –

Another abstract that caught our attention compared the treatment outcomes of “right vs. left” colon tumors.

Name:  “Impact of primary (1º) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance)”

Abstract Number:  Abstract 3504

Overview: The study retrospectively looked at how KRAS-wild type patients fared when given either bevacizumab or cetuximab as initial therapy. It appears that for patients with left-handed tumors (in the descending colon, sigmoid colon and rectum) it was beneficial to give cetuximab as the initial therapy. In contrast, for patients with a right-handed primary tumor (in the cecum and ascending colon), initial therapy with bevacizumab appears to be preferred.

Patients Need to Know:

• Ask your doctor which side your tumor appears – this could determine the best treatment plan for you.
• Request biomarker testing to determine if you have a KRAS-wild mutation. Download our fact sheet for more info.

FOLLOW THE CONVERSATION: June 3-7

ASCO takes place June 3-7. We will have several team members and volunteers on the ground sharing out the latest news from the front lines via social media. The best way to get real-time updates is to follow us on Twitter (@FightCRC) and the hashtag #ASCO16.

We’ll be sharing data released on numerous additional CRC experimental therapeutics, clinical trial results, researcher ideas and more. We’ll be asking the research community what they’re seeing as it relates to immunotherapy activity for non-MSI-high patients. This top 5 is just a summary and preview of what’s to come!

DON’T MISS IT – POST-ASCO WEBINAR

After ASCO, look for a follow-up report on the most significant news coming out of the meeting! ASCO is truly the “Super Bowl” of cancer research. It a unique opportunity to learn from global experts dedicated to the fight against cancer and to remind them that patients in the advocacy community are eager for answers and care about their work.

Vanderbilt’s Dr. Emily Chan will unpack and explain the CRC research from this year’s ASCO during our post-ASCO webinar on June 15. Make plans to attend so you know what to expect for CRC research in the months to come.

About Dr. Tom Marsilje

Dr. Tom Marsilje is a >20-year oncology research scientist with “currently incurable” stage IV non-MSI colon cancer and is a Colon Club 2016 Colondar 2.0 model. He also writes a personal blog on life at the intersection of being both a cancer patient and researcher “Adventures in Living Terminally Optimistic” and posts updates to Twitter @CurrentIncurSci. Tom is a Ph.D. scientist and not a M.D. He exclusively gives his opinions on the “science” of experimental therapies – nothing written should be misinterpreted as implying medical advice.

Funding Disclosure

Fight Colorectal Cancer has received funding from Merck (producers of pembrolizumab), Genentech (producers of cobimetinib, andatezolizumab & bevacizumab) and Lilly Oncology (producers of cetuximab) -- drugs mentioned in this article. Funding has come in the form of unrestricted educational grants. We maintain ultimate authority over website content and the content written in this article.