Exploring the Potential of Camu Camu in Metastatic Renal Cell Carcinoma

Regina Barragan-Carrillo, MD

A new study (NCT06049576) is exploring the potential of camu camu, known for its high polyphenol content, in combination with ipilimumab (Yervoy) and nivolumab (Opdivo) for treating metastatic renal cell carcinoma (mRCC).¹

The investigator-initiated, randomized, open-label, single-center trial is currently open for enrollment and plans to involve 30 patients who are treatment naive, with a primary focus on changes in the gut microbiome, specifically Ruminococcus spp. and its impact on treatment efficacy.

Patients will be randomized in a 2:1 ratio to receive either camu camu with standard dosing of ipilimumab and nivolumab or ipilimumab and nivolumab alone. Camu camu will be administered at a dose of 1500 mg daily. Once enrolled, patients will be followed monthly and continue treatment until disease progression or unacceptable toxicity, with response assessments via CT scans every 12 weeks.

The primary end point is the change in abundance of Ruminococcus spp. in stool samples from baseline to week 12 of therapy, and secondary end points include overall response rate, progression-free survival (PFS), safety, and changes in gut microbiome diversity, cytokine levels, and metabolic pathways.

Overall, the study aims to evaluate if camu camu can enhance the efficacy of ipilimumab and nivolumab by modulating the gut microbiome and improving immune responses.

In an interview with Targeted Oncology^TM, Regina Barragan-Carrillo, MD, medical oncologist, postdoctoral fellow, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, discussed the goals of this study and background on camu camu.

Kidney cancer, colorful medically 3D illustration: © Axel Kock - stock.adobe.com

Targeted Oncology: Could you discuss the rationale of this combination?

Barragan-Carrillo: This is a trial in progress. This trial is currently occurring for patients with intermediate- and poor-risk mRCC that has not undergone any type of systemic treatment. So as a standard –of care, we have plenty of options for the first-line treatment for renal cell carcinoma. One of them is a combination of nivolumab with ipilimumab. [Previously], we saw the results for the 8-year updated analysis, and we saw that the efficacy signal in both PFS and [overall survival (OS)] was still quite strong. Looking back, I am happy that we chose this combo for our trial. We are combining it with a fruit extract called camu camu.

Camu camu is a berry that grows in the Amazon region. It is part of the diet of people living in Brazil and also in Peru. Originally, they were using it as part of the treatment for patients who were either overweight or obese, and they noticed that the bacteria that was growing in the gut microbiome was on of those bacteria that were clearly associated with their response to immunotherapy. Those studies were initially done [preclinically], and then they were translated into human models. This is information we have had available for a couple of years. That was our rationale to use the combination. Additionally, we have a good collaborator in Canada who is doing similar trials for melanoma and non–small cell lung cancer.

How did you design your study to evaluate the efficacy and safety of this combination?

We are doing a randomized phase 1 trial with a 2:1 randomization. Most patients are going to be exposed to the experimental compound camu camu. I do want to highlight that the safety we have with this agent has been quite successful. The rationale for our design is, at this moment, based on biological biomarkers. We are using the end point of an increase in Ruminococcus, which is a bacterium I was just mentioning, that we saw in the initial studies with patients with obesity. We are keen on understanding, at this point, whether there is a biological rationale to using these components. We have secondary end points, also overall response rate, progression-free survival, and safety. We will be looking at these to see whether there is a signal of important activity or not, but right now, our main goal is to understand biological activity.

What does the eligibility criteria include for the study?

Metastatic or advanced renal cell carcinoma of clear cell histology can or cannot have sarcomatoid components. Also, they should not have had prior treatment with a PD-(L)1 or CTLA-4 inhibitor and should have adequate organ function. We use the combination following all the safety requirements.

What are the potential advantages of using camu camu in this context?

I started in Mexico, and I am very proud of it. Addressing interventions that are cost effective and that are going to be accessible worldwide [is important]. Another important reason for it is that the added toxicity of these compounds right now do not seem to be important. This will likely be a safe add-on to the combination we have. Finally, I think right now we are early on exploring the impact that the microbiome has on the immune response, and this is quite important. This is going to help us to determine the best treatments in the upcoming years.

REFERENCE:

Barragan-Carrillo R, Chawla NS, Salgia, N, et al. Combination nivolumab and ipilimumab with and without camu camu in first-line treatment of metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2024;42(suppl 4):TPS491. doi:10.1200/JCO.2024.42.4_suppl.TPS491