Study Shows Potential for Nivolumab/Ipilimumab Combo in CRC

Article

The combination of nivolumab (Opdivo) and ipilimumab showed efficacy in a recent study looking at patients with colorectal cancer (CRC), according to Michael Overman, MD.

In an interview withTargeted Oncology, Overman, associate professor, department of gastrointestinal medical oncology, division of cancer medicine, the University of Texas MD Anderson Cancer Center, discusses the recent CHECKMATE-142 study, which looked at nivolumab and ipilimumab in recurrent and metastatic CRC.

TARGETED ONCOLOGY:Can you tell us about the recent study of nivolumab and ipilimumab in CRC?

Overman:We presented the abstract from the CHECKMATE 142 study, which looked at nivolumab and ipilimumab in microsatellite instability-high CRC. This is a subset that's shown previously immune responsiveness, and at ASCO we demonstrated our interim results with 70 patients treated with nivolumab, and 30 patients treated with nivolumab and ipilimumab.

These results in particular demonstrate as previously shown, marked activity with checkpoint therapy in this particular type of colon cancer. We have a PFS that's around 6 months with single-agent nivolumab, and the more impressive findings related to our data is the durability of our responses and the stable disease.

Our progression-free survival at 12 months with single-agent nivolumab is approximately 45%, really demonstrating that patients that are on therapy for greater than 12 weeks, at that point really stay on therapy for the remainder. We see very few late progression events. In an overall sense, we do see both partial response and stable disease in about 30% for each, but those seem to be durable and in both cases.

In regards to the combination therapy, again that's a smaller cohort that started later in this study design, so the follow-up is a shorter time period for the combination. A least preliminarily in regards to tumor reduction, 80% of cases have demonstrated a reduction in size. If you look at the monotherapy of ipilumimab, you have approximately 55% with tumor reduction, so it does appear that there's potentially more benefit from combination therapy, but again I would like to stress that monotherapy is fairly dramatic in regards to the activity that we're seeing, and the durability of those kind of responses and stable disease.

Within this study, there was a microsatellite stable cohort that was used to determine the dose for the combination arm. So that was the purpose of having this very small, 20 patient microsatellite stable cohort. Based on that cohort, the safety data demonstrated that we moved forward with combination arm of nivolumab of 3 mg/k and ipilumimab at 1 mg/k. Within that 20 patient cohort, we had 1 response, and in general the progression-free survival was fairly short at about 2 months.

TARGETED ONCOLOGY:What role do you envision immunotherapy having in this disease?

Overman:I think it's really exciting. There's been pembrolizumab data and the nivolumab findings kind of support the information that was seen in that data set. Our data set is a little larger in sample size at this point, so I think we robustly confirm the activity of PD-1 targeting. Both assets really show a dramatic level of activity. We're seeing some of the highest response stable disease rates that we've seen in many different types of solid tumors with immune checkpoint therapy.

This subset is going to be defined as an immune therapy subset, meaning they will be treated with immune therapy. Going forward, I think we're going to see these immune checkpoints being moved into earlier lines of therapy. There's already studies that are investigating that. The question that's really open now and is of great interest is "do they really just replace chemotherapy in the MSI-high population?" I think there's some early data in the refractory base that shows that that could really be the case, but how that works out or if there's a combination approach that's best is what will play out in the future.

TARGETED ONCOLOGY:Are there any next steps for this?

Overman:This study is still ongoing. it was a two-stage design with monotherapy and combination therapy, and so the second stage of the combination therapy is still open and still enrolling. Clearly we need more follow-up from the combination arms, because those were started later based on the design, so the followup is much shorter. The first future step would be to further follow-up on this data.

Related Videos
Rohit Gosain, MD; Rahul Gosain, MD; and Pamela L. Kunz, MD, presenting slides
Rohit Gosain, MD; Rahul Gosain, MD; and Pamela L. Kunz, MD, presenting slides
Related Content