Pre-ASCO 2017 MSS-CRC Immunotherapy Breaking News: RO6958688 + anti-PDL1
ASCO-2017 abstracts were released yesterday and there is one study that really stood out for MSS-CRC: Abstract 3002. The study is for the ongoing clinical trial #NCT02650713 which is testing an exploratory CEA x CD3 bifunctional protein immunotherapy called “RO6958688” both with & without the addition of the PDL1 inhibitor Atezolizumab (Tecentriq).
I have been tracking this clinical trial for months as I have steadily seen multiple anecdotal accounts of successful activity appear on multiple patient message boards as patients self-reported their CT-scan results while they were on trial.
Now that the official abstract data has been released, I wanted to publish the released abstract data, while we wait for the full data presentation in a few weeks at ASCO-2017. Once the full data is released, I’ll write up a full blog post in layperson language on both the complete data and an explanation of the scientific approach used. I wrote a short piece on a closely related drug, using similar “CEA-targeting bifunctional” methodology, almost two years ago here. I have always liked the bifunctional approach to attacking a “cold tumor” (i.e. a tumor resistant to immunotherapies) like MSS-CRC since it is very brute force and in those kind of situations, sometimes brute force is exactly what you need!
Here is a brief overview of the efficacy data from the abstract (I am going to focus on the patients who got the combination of both RO6958688 and Atezolizumab). In the 10 patients who received 60 mg or more of RO6958688 + Atezolizumab:
- 1 patient (10%) had a “partial response” (tumor shrinkage of >30%)
- 5 additional patients (50%) had “stable disease” but showed tumor shrinkage in the range of 10-30%
- There were toxicities seen due to RO6958688 (it is a very powerful drug!), all of which were deemed to be related to its immune-activation/inflammation mechanism of action but there did not seem to be additional toxicity due to the addition of Atezolizumab.
One biotech/drug discovery news source summarized the data here.
Taken all together – this is very promising although it must be noted that the study size of the combination is still very small as of this data release (only 10 patients). Due to the high number of responses seen within that small group, I am personally sure that RO6958688 and Atezolizumab has clinical activity but determining the exact % of patients who will respond will require testing in significantly more patients (the trial continues – in progress!). The toxicities will also need to be further examined and identified (and management techniques refined) as the combo is tested in more patients. Finally, it remains to be seen how “durable” (long lasting) the effects are for this treatment since it is plausible that tumors could mutate their CEA target away from the drug, similar to how mutations develop for targeted therapies. Only time and continued clinical data will tell…
Believe it or not I still hear daily from patients that their oncologists tell them that it is impossible for MSS-CRC to respond to immunotherapies. Although that statement has been proven false already in the past, hopefully this study’s results will be yet another data point to the larger oncologist community that Hard does not equal impossible! That is a point I have been trying to drive home on this blog for two years now (sometimes feeling like a lone voice in the wilderness!)
I am confident that in addition to this study being released at ASCO-2017, there will be additional immunotherapy progress published/presented for MSS-CRC in 2017. The MSS-CRC immunotherapy train is on the tracks and it is picking up steam!
Stay tuned for a follow-up post on this exciting new experimental immunotherapy combination for MSS-CRC in a few weeks!