FDA Approves New Pembrolizumab CDx to Identify pMMR in Endometrial Cancer

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

The label expansion follows prior approvals, including 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. Additionally, the FDA approved the VENTANA MMR RxDx panel as a companion diagnostic for treatment with the combination of pembrolizumab and lenvatinib (Lenvima) for patients with pMMR solid tumors in June 2022.

This companion diagnostic is designed to test MMR proteins in tumors to provide treatment information to experts. It is the first immunohistochemistry (IHC) companion diagnostic test which can help in identifying patients whose solid tumors are deficient in dMMR, and who may be eligible for pembrolizumab. Additionally, it is the first of its kind that can help to identify patients with endometrial cancer whose tumors are proficient in pMMR, and who may be eligible to receive pembrolizumab and lenvatinib.

“Roche is committed to advancing personalized health-care options for all solid tumor patients,” stated Jill German, head of Pathology at Roche Diagnostics, 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.”

The qualitative IHC test, VENTANA MMR RxDx, also is designed to assess the various MMR proteins, including 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 to be effective and predictive biomarkers for PD-L1–targeted therapy as the loss of expression of 1 or more MMR proteins can potentially increase the chances of responding to such therapy.

The FDA has also approved various other combinations and monotherapies for the treatment of patients with dMMR and pMMR. In June 2020, theFDA approved pembrolizumab monotherapy for the frontline treatment of patients with unresectable or metastatic microsatellite instability–high (MSI-H) or dMMR colorectal cancer.

Then in April 2021, the FDA granted accelerated approval to dostarlimab-gxly for the treatment of adult patients with recurrent or advanced endometrial cancer that progressed on or following prior treatment with platinum-containing chemotherapy and whose cancers have a specific genetic feature known as dMMR, as determined by an FDA approved test.

In July 2021, the FDA approved the combination of pembrolizumab plus lenvatinib as a treatment as an option for patients with advanced endometrial carcinoma that is not 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.

This approval of pembrolizumab plus lenvatinib was based on data from the phase 3 KEYNOTE-775/Study 309 trial (NCT03517449) which showed that pembrolizumab/lenvatinib produced a median overall survival of 17.4 months (95% CI, 14.2-19.9) vs 12.0 months (95% CI, 10.8-13.3) for chemotherapy in this patient population (0.68; 95% CI, 0.56-0.84; P = .0001).

The combination also showed a median PFS of 6.6 months (95% CI, 5.6-7.4) vs 3.8 months (95% CI, 3.6-5.0) for chemotherapy (HR, 0.60; 95% CI, 0.50-0.72; P <.0001). In the pembrolizumab/lenvatinib arm, the ORR was 30% (95% CI, 26%-36%) while in the chemotherapy arm it was 15% (95% CI, 12%-19%).

In March 2022, theFDA also granted approval to single-agent pembrolizumab for the treatment of patients with advanced endometrial carcinomathat 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.

This approval was based on new data from cohorts D and K of the KEYNOTE-158 trial (NCT02628067) which revealed the objective response rate (ORR) to be 46% (95% CI, 35-56) for patients who received pembrolizumab.

References

1. Roche receives FDA approval for VENTANA MMR RxDx Panel to identify dMMR solid tumor patients and pMMR endometrial cancer patients eligible for KEYTRUDA. News release. Roche. August 11, 2022. Accessed August 12, 2022. https://prn.to/3QCPHiZ