Triplet Therapy Shows Promise in Advanced Lung Cancer

A combination of an antibody-drug conjugate, immune checkpoint inhibitor and chemotherapy is showing promise for patients with metastatic non-small cell lung cancer. Results from the phase 2 EVOKE-02 study will be presented at the 2024 World Conference on Lung Cancer.

Researchers investigated the combination of sacituzumab govitecan, pembrolizumab and carboplatin, a type of chemotherapy, as a first-line treatment for the disease.

Sacituzumab govitecan is an investigational antibody-drug conjugate that targets a cell surface protein that is overexpressed in many types of cancers. The antibody targets and binds to the protein, directing the drug to attack the cancer cells while sparing healthy tissue.

Pembrolizumab is an immune checkpoint inhibitor that targets and blocks the programmed cell death protein 1 receptor on T cells, keeping cancer cells from suppressing the immune system.

Jhanelle Gray, MD

“EVOKE 02 is an innovative and unconventional approach whereby we replace the traditional first-line platinum-based doublet chemotherapy regimens,” said Jhanelle Gray, MD, chair of the Thoracic Oncology Department at Moffitt Cancer Center and the presenting author of the study. “In non-squamous non-small cell lung cancer, we are replacing pemetrexed, and in squamous non-small cell lung cancer, we are substituting taxanes with sacituzumab govitecan.”

Participants received all three treatments on the first day of a 21-day cycle, followed by another dose of sacituzumab govitecan on day eight. This continued over four cycles, followed by maintenance therapy.

The combination of drugs showed promising results in patients with both non-squamous and squamous metastatic non-small cell lung cancer. Most patients had a PD-L1 tumor proportion score of less than 50%. Initially, around two-thirds of patients showed low levels of neutrophils, which are a type of white blood cell crucial for fighting off infections.

By reducing the dose size of sacituzumab govitecan, the number of patients experiencing low neutrophils was less than 25%.

Researchers are encouraged by the efficacy of the combination therapy in patients with non-actionable genetic alteration driven metastatic non-small cell lung cancer, particularly those with lower PD-L1 expression. The safety profile with the reduced sacituzumab govitecan dose also proved to be manageable.

“While we need more data to move this treatment forward, we continue to research sacituzumab govitecan in different combinations across other studies including EVOKE-01 and EVOKE-03,” Gray said. “We’re looking forward to presenting those results at future meetings.”