Zejula-Jemperli Combo Shows Promising Responses in Breast Cancer Subset

A small cohort of patients with germline BRCA-mutated estrogen receptor (ER)-positive, HER2-negative breast cancer demonstrated responses after receiving a combination of neoadjuvant Zejula (niraparib) plus Jemperli (dostarlimab-gxly), according to data from group C of the phase 2 TBCRC-056 trial presented at the 2024 San Antonio Breast Cancer Symposium.

Data showed that the pathological complete response rate (pCR) was 16.7%. Additionally, the residual cancer burden (RCB) score of zero or 1 was 44.4%, the RCB score of 1 was 27.8%, the RCB score of 2 was 22.2%, the RCB score of 3 was 22.2% and those given additional neoadjuvant therapy had a response rate of 11.1%.

“Given the activity of preoperative PD-1 inhibition for ER-positive breast cancer, additional evaluation of targeted non-chemotherapy approaches is of great interest in this patient population,” Dr. Erica L. Mayer, director of Clinical Research and Institute Physician at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, both in Boston, said during the presentation.

To be eligible for treatment, patients needed to have germline BRCA1/2 mutations or germline PALB2 mutations, HER2-negative disease, stage 1 to 3 disease and a tumor of 1 centimeter or more. Between groups A, B and C, 64 patients were enrolled.

The median patient age was 41.8 years old, and 77.8% were White. At diagnosis, most patients had stage 2 disease (44.4%) followed by stage 1 (38.9%) and stage 3A (16.7%). Of note, the majority of patients had a tumor grade of 2 (61.1%). A germline BRCA1 mutation was observed in 27.8% of patients versus 72.2% with BRCA2.

Regarding treatment exposure, 18 patients have completed therapy and received surgery. Before surgery, two patients were given additional neoadjuvant therapy, 83.3% completed six cycles of Zejula and 61.1% completed six cycles of Jemperli.

Regarding toxicity, the most common grade 3 (severe) treatment-related side effects included rash (27.8%), increased levels of alanine transaminase (16.7%) and nausea (5.6%).

Study investigators of group C evaluated 18 patients with ER-positive, HER2-negative disease who were given Zejula plus Jemperli for 18 weeks. Zejula was given at 200 mg by mouth daily, and Jemperli was given at 500 mg intravenously every three weeks. Patients were enrolled between April 2021 and May 2024.

Regarding the background for this research, the pCR rates observed in those with triple-negative breast cancer have approximately been 50% for those receiving neoadjuvant PARP inhibitor therapy. This form of treatment is a type of targeted therapy that helps repair damaged DNA, according to The University of Texas MD Anderson Cancer Center.

Mayer noted that further research regarding TNBC was underway.

Although previous data suggested that adding an anti-PD-L1 therapy to a PARP inhibitor did not increase activity in patients with BRCA-mutated breast cancer, there may be room for this combination in less immunosuppressed early-stage settings.

“Additional exploration of the immunosuppressive components of the tumor microenvironment may help fully realize the impact of combining immunologic approaches with PARP inhibition,” Mayer concluded.

Reference

“TBCRC 056: a phase II study of neoadjuvant Zejula with Jemperli for patients with BRCA- or PALB2-mutated breast cancer: results from the ER+/HER2- cohort” By Dr. Erica L. Mayer, et al. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, Texas.

Study highlights

A small group of patients with germline BRCA-mutated ER-positive, HER2-negative breast cancer showed responses to a combination of Zejula (niraparib) and Jemperli (dostarlimab-gxly) in the TBCRC-056 trial.

The pathological complete response (pCR) rate was 16.7%, and 44.4% of patients had a residual cancer burden (RCB) score of zero or 1.

The combination treatment was generally well-tolerated, though common severe side effects included rash (27.8%), increased liver enzymes (16.7%), and nausea (5.6%).