Addition of bacterial product to kidney cancer regimen may delay disease progression
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Key takeaways:
- CBM588 added to cabozantinib and nivolumab did not increase Bifidobacterium spp., which researchers hypothesized would occur.
- The triplet demonstrated a significant increase in PFS.
CHICAGO — The addition of CBM588 to immune checkpoint inhibitor-based therapy significantly increased PFS and response rates with no impact on stool microbiome diversity among a small cohort of patients with metastatic renal cell carcinoma.
“The addition of CBM588 to cabozantinib and nivolumab was associated with no significant increase in Bifidobacterium spp., which was the primary endpoint of the study,” Hedyeh Ebrahimi, MD, MPH, a noncommunicable diseases researcher at City of Hope, said during a presentation. “Our results bolster previous clinical data associated with nivolumab/ipilimumab [Yervoy, Bristol Myers Squibb] with CMB588 in metastatic renal cell carcinoma.”
Background and methodology
Renal cell carcinoma represents approximately 3% of all malignancies, according to study background. Front-line systemic therapy for metastatic clear cell RCC consists of dual checkpoint inhibitor therapy and combination therapy with checkpoint inhibitors and VEGF-directed therapy.
CBM588 (Miyarsian Pharmaceutical), a live bacterial product that contains a strain of Clostridium butyricum, has been shown to potentially augment clinical outcomes of patients with metastatic RCC who receive dual immune checkpoint inhibitors as first-line therapy, according to researchers.
Ebrahimi and colleagues sought to determine the effect of CBM588 on outcomes when added to cabozantinib (Cabometyx, Exelixis), a multitargeted tyrosine kinase inhibitor, and nivolumab (Opdivo, Bristol Myers Squibb) a PD-1 immune checkpoint inhibitor.
The study included 30 adults (median age, 65; range, 36-84) with histologically verified metastatic renal cell carcinoma and a Karnofsky performance score of 70% or greater who had received no prior systemic treatment for metastatic disease. Among them, 17% had sarcomatoid features and 7% had predominant papillary histology. In addition, 40% had good-risk, 40% had intermediate-risk and 20% had poor-risk disease.
Researchers randomly assigned patients 2:1 to cabozantinib and nivolumab with (n = 20) or without (n = 10) CBM588.
All patients received 40 mg oral cabozantinib daily and 480 mg IV nivolumab monthly, with those in the investigative group also receiving 80 mg oral CBM588 twice daily.
Relative abundance of Bifidobacterium spp. in stool specimens at baseline and after 12 weeks of treatment served as the primary endpoint. Secondary endpoints included assessment of response rate, OS, PFS, systemic immunomodulation and toxicity.
Researchers used a two-group t-test with a one-sided type I error of 0.05 to assess the study’s primary endpoint, They hypothesized an increase of Bifidobacterium spp. in patients who received CBM588 therapy.
Results
Researchers found no significant difference from baseline to week 12 in relative abundance of Bifidobacterium spp. or in alpha diversity in the control group or the CBM588 group.
“It is curious that certain species of Ruminococcaceae appear to be enriched at week 12 in patients receiving CBM588,” Ebrahimi said. “However, it is not consistent across the genus, as several species appear to be depleted, as well, at the same timepoint.”
Researchers reported numerical improvement in response rate with the CBM588 regimen vs. cabozantinib and nivolumab alone, with a partial response rate of 56% vs. 25%, as well as a higher clinical benefit rate (89% vs. 61%).
The CBM588 cohort did not reach median PFS, compared with median PFS of 5.8 months with cabozantinib and nivolumab.
Grade 3 to grade 4 toxicities occurred in 44% of patients in the control group and 42% of patients in the experimental group, although Ebrahimi noted that the small sample size challenges interpretation of these results.
Additional research into the agent’s impact on this patient population is pending, she said.
“Given the compelling evidence from two investigator-initiated studies at our institution, we feel that further assessment of CBM588 should be prioritized,” Ebrahimi said. “We are eager about ongoing discussions between the cooperative groups for potential phase 3 designs involving this agent.”
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Ebrahimi H, et al. Abstract LBA104. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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