FDA Approves VENTANA MMR RxDx To Identify dMMR Solid Tumors and as Companion Diagnostic for pMMR Endometrial Cancer

FDA

The FDA has expanded its approval of the VENTANA MMR RxDx panel to identify patients with mismatch repair–deficient (dMMR) solid tumors and as a companion diagnostic assay to determine eligibility for pembrolizumab (Keytruda) as a treatment for patients with mismatch repair–proficient (pMMR) endometrial cancer.¹

The companion diagnostic is designed for the assessment of MMR proteins, which is tested via immunohistochemistry (IHC). The label expansion follows prior approvals, including as a companion diagnostic for treatment with dostarlimab-gxly (Jemperli) for patients with advanced or recurrent endometrial cancer in August 2021 and as a companion diagnostic for treatment with pembrolizumab for patients with dMMR solid tumors in March 2022^.2,3 The agency approved the panel as companion diagnostic for treatment with pembrolizumab plus lenvatinib (Lenvima) for patients with pMMR solid tumors in June 2022.¹

“Roche is committed to advancing personalized health-care options for all solid tumor patients,” Jill German, head of Pathology at Roche Diagnostics, stated in a news release. “As the first companion diagnostic of its kind, our test provides patients with access to multiple therapies, enabling targeted treatment. We are pleased that our innovative companion diagnostic portfolio continues to grow to serve more patients.”

VENTANA MMR RxDx is a qualitative IHC test designed for use in assessing the MMR proteins MLH1, PMS2, MSH2, and MSH6. The proteins are assessed in formalin-fixed, paraffin-embedded tumor tissue stained with the OptiView DAB IHC Detection Kit is used for MLH1, MSH2 and MSH6, and the OptiView DAB IHC Detection Kit with the OptiView Amplification Kit is used for PMS2 on a BenchMark ULTRA instrument.

MMR proteins have been proven as effective predictive biomarkers for PD-L1–targeted therapy because the loss of expression of 1 or more MMR proteins could increase the chances of responding to such therapy.

For patients with advanced endometrial cancer, the distinction between dMMR and pMMR can lead to different therapy choices. In June 2021, the FDA granted regular approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability–high (MSI-H) or dMMR, who have disease progression after previous systemic therapy in any setting, and who are not candidates for curative surgery or radiation.⁴

In March 2022, the FDA approved to single-agent pembrolizumab for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, who experienced disease progression following previous systemic therapy in any setting and are not candidates for curative surgery or radiation.³

The 2021 approval of pembrolizumab plus lenvatinib for non–MSI-H/dMMR advanced endometrial carcinoma was based on findings from the phase 3 KEYNOTE-775/Study 309 trial (NCT03517449). Pembrolizumab/lenvatinib produced a median overall survival of 17.4 months (95% CI, 14.2-19.9) compared with 12.0 months (95% CI, 10.8-13.3) for chemotherapy in patients with advanced endometrial cancer that is not MSI-H or dMMR (HR, 0.68; 95% CI, 0.56-0.84; P = .0001).⁴

The median PFS was 6.6 months (95% CI, 5.6-7.4) for the combination and 3.8 months (95% CI, 3.6-5.0) for chemotherapy (HR, 0.60; 95% CI, 0.50-0.72; P <.0001). The overall response rate (ORR) was 30% (95% CI, 26%-36%) in the pembrolizumab/lenvatinib arm compared with 15% (95% CI, 12%-19%) for the chemotherapy arm.

The 2022 approval of single-agent pembrolizumab for advanced MSI-H/dMMR endometrial cancer stemmed from findings from the phase 2 KEYNOTE-158 trial (NCT02628067). The immunotherapy agent produced an ORR of 46% (95% CI, 35%-56%).³

References

1. Roche receives FDA approval for VENTANA MMR RxDx Panel to identify dMMR solid tumour patients and pMMR endometrial cancer patients eligible for KEYTRUDA. News release. Roche. August 11, 2022. Accessed August 11, 2022. https://prn.to/3Qk43VP
2. Roche receives FDA approval for first companion diagnostic to identify dMMR solid tumour patients eligible for anti-PD-1 immunotherapy. News release. Roche. August 18, 2021. Accessed August 11, 2022. https://bit.ly/3gdP7sg
3. FDA approves pembrolizumab for advanced endometrial carcinoma. News release. FDA. March 21, 2022. Accessed August 11, 2022. https://bit.ly/3Qx9Kzo
4. FDA grants regular approval to pembrolizumab and lenvatinib for advanced endometrial carcinoma. News release. FDA. July 22, 2021. Accessed August 11, 2022. https://bit.ly/3wRB9Sw