Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC).Johanna C. Bendell, Tae Won Kim, Boon C. Goh, Jeffrey Wallin, Do-Youn Oh, Sae-Won Han, Carrie B. Lee, Matthew David Hellmann, Jayesh Desai, Jeremy Howard Lewin, Benjamin J. Solomon, Laura Quan Man Chow, Wilson H. Miller, Justin F. Gainor, Keith Flaherty, Jeffrey R. Infante, Meghna Das-Thakur, Paul Foster, Edward Cha, and Yung-Jue Bang
Journal of Clinical Oncology 2016 34:15_suppl, 3502-3502
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Results: As of October 12, 2015,
23 CRC (22 KRAS mutant, 1 WT) pts were enrolled during escalation and expansion. No dose-limiting toxicities were observed, and expansion occurred at atezo 800 mg q2w and cobi 60 mg. Median follow-up for safety in CRC pts was 3.78 mo (range, 1.1-11.7). The most common treatment-related AEs included diarrhea (69.6%), fatigue (52.2%), dermatitis acneiform (43.5%), rash (34.8%), maculopapular rash (26.1%), pruritus (26.1%) and nausea (26.1%). Incidence of treatment-related G3-4 AEs was 34.8%. The only treatment-related G3-4 AE in ≥ 2 pts was diarrhea (8.7%). No G5 AEs were reported. The ORR was 17% (4 PR, 5 SD).
Three responses were ongoing (range, 4.0 to 7.7 mo at time of data cutoff).
Three responders were mismatch repair-proficient [that means: MSS], and 1 was unknown. Response was not associated with baseline PD-L1 expression. Results from the serial biopsy cohort showed enhanced PD-L1 upregulation, CD8 T-cell infiltration and MHC I expression on treatment, providing mechanistic rationale for the combination.
Conclusions: The combination of cobi and atezo in CRC is well tolerated at the maximum administered doses.
These results show that pts with MSS CRC can respond to the combination of cobi and atezo, and provide support for continued evaluation of the combination. Clinical trial information: NCT01988896.
http://ascopubs.org/doi/abs/10.1200/JCO ... suppl.3502