Hedyeh Ebrahimi: Intrigued by the difference in response between CBM588 and ctrl arms
Hedyeh Ebrahimi, Postdoctoral fellow at Genitourinary Cancer Research Team of City of Hope shared a thread on X:
“It’s with great pleasure that I share with you our paper evaluating cabozantinib with nivolumab +/- CBM588 in patients with advanced kidney cancer, published today in Nature Medicine!
Huge thanks 1st and foremost to patients and their families. Had tons of support from the amazing at city of hope/at Translating Genomic Research team and guidance from my mentor Sumanta K. Pal.
It was my co-first author and hero Nazli Dizman at MD Anderson News (and team – Paulo G Bergerot, Luis A. Mezaco et al) who paved the path to this trial with her previous paper in Nature Medicine suggesting that CBM588, a live bacterial product, could augment outcomes with nivolumab/ipilimumab.
We randomized 30 patients with metastatic kidney cancer to receive cabo/nivo +/- CBM588. Patients had clear cell or papillary histology. The primary EP in this study was biologic – namely, change in Bifidobacterium spp, akin to our previous trial. This was predicated on changes we anticipated in the gut flora with the expansion of Clostridium butyricum, a butyrate-producing species.
Ultimately, we did not see the anticipated changes in Bifidobacterial species. However, we did see some enrichment in Ruminococcaceae species – based on studies by Dr Rebecca Simpson, Professor Richard Scolyer, Professor Georgina Long, Jennifer Wargo and others, it is possible that this could aid in facilitating Immuno-Oncology response.
What we were really intrigued by is the difference in response between CBM588 and ctrl arms. Of note, the difference in PFS was more modest than when I previously reported the data at ASCO23. We MUST acknowledge the small sample size here – we elaborate on the implications/limitations of our work in the Discussion.
So, where do we go from here? I am pleased to hear that Pedro C. Barata, Sumata K. Pal, Ulka Vaishampayan are driving a SWOG trial that will evaluate CBM588 in the context of a P3 study.
Also, my comentor Alex Chehrazi Raffle is running a P1 trial that will evaluate dose escalation of CBM588 with nivo/ipi.
The microbiome field is so exciting. I have been inspired by the trail blazers in the microbiome field – Jennifer Wargo Zitvogel, Bertrand Routy, SM Immunology, Diwakar Davar, Lisa Derosa, Jennifer Mcquade, Arielle Elkrief and so many others. We are lucky to have leaders in the microbiome space at city of hope, including Dr Marcel Van Den Brink, Greg Caporaso and other individuals soon to join us. As I continue my time at city of hope ahead of residency, hoping to dig deeper into the story told here!
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Source: Hedyeh Ebrahimi/X