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Clinical Trial
. 2025 Oct 1;30(10):oyaf305.
doi: 10.1093/oncolo/oyaf305.

Phase II single-arm study of palbociclib and cetuximab in anti-EGFR naïve patients with KRAS/NRAS/BRAF wild-type, metastatic colorectal cancer

Jonathan D Sorah  1 , Dominic T Moore  1 , Matthew J Reilley  2 , Mohamed E Salem  3 , Tammy Triglianos  1 , Autumn J McRee  4 , Michael S Lee  4 , Hanna K Sanoff  1 , Ashwin S Somasundaram  1
Affiliations
Clinical Trial

Phase II single-arm study of palbociclib and cetuximab in anti-EGFR naïve patients with KRAS/NRAS/BRAF wild-type, metastatic colorectal cancer

Jonathan D Sorah et al. Oncologist. .

Abstract

Background: Standard therapy for patients with KRAS/NRAS/BRAF wild-type (WT), microsatellite stable (MSS), L-sided metastatic colorectal cancer (mCRC) often includes chemotherapy with a monoclonal antibody (mAb) that targets epidermal growth factor receptor (EGFR) such as cetuximab. Preclinical studies suggest the role of CDK4/6 activity downstream of EGFR as a possible resistance mechanism to anti-EGFR therapy. Therefore, we hypothesized that the addition of the CDK4/6 inhibitor palbociclib would increase the disease control rate of patients with anti-EGFR naïve KRAS/NRAS/BRAF-WT mCRC.

Methods: LCCC1717 was a phase II trial with a Simon two-stage design in which patients with KRAS/NRAS WT mCRC having progressed on at least two lines of therapy were given palbociclib and cetuximab. The primary end point was four-month disease control rate (DCR). Secondary endpoints were overall survival (OS) and progression-free survival (PFS). If six or more patients achieved disease control at four months, the study would continue enrollment, otherwise the study would be discontinued.

Results: A total of 12 subjects were enrolled, 11 of whom had left-sided colon cancer. The four-month DCR was 41.7% (95% CI 15% to 72%) with median OS at 13.9 months and median PFS of 5.3 months, which did not meet the pre-specified endpoint of efficacy. The treatment combination was well tolerated with the most common treatment-related toxicity being decreased lymphocyte and neutrophil counts.

Conclusion: While clinical benefit was observed with the combination, it did not meet its pre-specified endpoint for efficacy in patients with KRAS/NRAS/BRAF WT EGFR therapy-naïve mCRC patients. Clinicaltrials.gov Identifier: NCT03446157.

Keywords: cetuximab; colon cancer; palbociclib.

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Conflict of interest statement

Matthew J. Reilley: Research Funding: Astrazeneca, Amgen, Abbvie, Cardiff Oncology, Crinetics, Genfit, Macrogenics, Merck, Pfizer, RayzeBio, Surface Oncology, Xencor Consulting/Advisory: Cardiff, Incyte, Natera, NEJM group, Pfizer; Autumn J. McRee: JNJ Employment; Michael S. Lee: I am now employed by Johnson & Johnson; Hanna K. Sanoff: Research funding to Institution: Abbvie, Amgen, Astra Zeneca, Bristol Myers Squibb, Pfizer, Rgenix, Johnson & Johnson.

Figures

Figure 1.
Figure 1.
Best response per patient.
Figure 2.
Figure 2.
Progression-free survival.
See this image and copyright information in PMC

References

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