Use of Navtemadlin After Failure of Immunotherapy in Merkel Cell Carcinoma

By: Victoria Kuhr, BA
Posted: Monday, June 13, 2022

A phase Ib/II study is examining the MDN2 inhibitor navtemadlin as a potential single-agent therapeutic option for patients with TP53 wild-type Merkel cell carcinoma who did not benefit from anti–PD-1/PD-L1 therapy. According to Michael K.K. Wong, PhD, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues, upregulation of the p53 pathway may be a viable therapeutic strategy for patients with this type of skin cancer. The 180-mg dose of navtemadlin has been selected for further evaluation. These findings were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9506).

The study enrolled patients with TP53 wild-type Merkel cell carcinoma after failure of anti–PD-1/PD-L1 therapy. The patients were randomly assigned to once-daily oral doses of navtemadlin in 21- or 28-day cycles until disease progression or toxicity.

By November 2021, 31 patients were enrolled in the study. The median patient age was 66 years. Of this population, 52% had visceral disease, and 71% had received more than two lines of prior therapy. All baseline tumor profiling samples showed low tumor mutation burden and nonamplified MDM2 gene. Additionally, 92% of baseline samples showed Merkel cell polyomavirus positivity.

All patients reported treatment-emergent adverse events, 68% of which were grade 3 or 4. The most common grade 3 or 4 treatment-emergent adverse events were hematologic anemia (32%), lymphopenia (32%), and thrombocytopenia (19%). According to the investigators, the doses of navtemadlin less than 180 mg were well tolerated, and patients so treated needed fewer dose reductions.

Patients receiving 180 mg on a 5-days-on and 23-days-off cycle had a 25% confirmed objective response rate, a 38% unconfirmed plus confirmed objective response rate, and a 63% disease control rate. The median time to treatment response was 4.1 months. After a prolonged partial response, one patient achieved complete metabolic remission after 2 years of treatment.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2022 ASCO Annual Meeting