SAN JUAN, Puerto Rico – Nearly 100% of patients with recurrent/metastatic endometrial cancer benefited from an investigational specific antibody and standard chemotherapy, according to a small preliminary study from China.
Among 41 efficacy-evaluable patients, 32 had objective responses and eight had stable disease with chemotherapy plus cadonilimab, an antibody targeting PD-(L)1 and CTLA-4. The group had a median progression-free survival (PFS) of approximately 18 months, and the median overall survival (OS) has yet to be reached. Patients with mismatch repair-deficient (dMMR) tumors had better PFS, but OS appeared similar in patients with and without MMR deficiency.
Yang Sun, MD, of the School of Clinical Oncology of Fujian Medical University in China, reported at the Society of Gynecological Oncology meeting that less than 20% of patients had grade 3/4 treatment-related adverse events (TREEs), with skin rashes and allergies being the most common.
“Cadonlimab combined with standard chemotherapy showed promising antitumor activity as a first-line treatment for advanced or recurrent endometrial cancer,” Sun said. “In addition, the combination has a favorable and manageable safety profile. In the next phase, our team will focus on potential biomarker and mechanistic research.”
Immune checkpoint inhibitors have occupied the standard of care space for advanced disease, but have begun to move into the adjuvant setting following favorable results from trials such as RUBY, NRG-GY018, DUO-E and others. Keynote Speaker-B21. Specific antibodies offer a potential option to fill that niche and perhaps eventually move into previous lines of treatment.
“It’s phenomenal to see something so specific in this location,” said invited discussant Bradley Corr, MD, of the University of Colorado Cancer Center in Aurora. “This bispecific antibody is different in that it utilizes both the PD-L/L1 and CTLA-4B7 connections of the antigen-presenting cell and the T cells. The bispecific antibody directly binds T cells to tumor cells to target destruction, whereas immune checkpoint inhibitors release the brakes on existing T cells.”
He further said, some questions remain to be answered and perhaps they will be addressed in a publication. More than half of the patients in the trial had recurrent disease, which may impact the risk of subsequent recurrence. No information was provided about prior radiation therapy which may also affect recurrence risk.
The study showed “excellent” safety data, Core said, which would encourage use of the drug and potentially help it be taken to earlier disease states.
Sun reports findings from Phase II, single-arm primary analysis care tests. The investigators enrolled 47 patients, of whom 45 were included in data analysis, 17 had stage I disease and 28 had stage II disease. All patients received six to eight cycles of cadonilimab plus carboplatin/paclitaxel chemotherapy. Patients with minimally stable disease after induction received cadonilimab maintenance for up to 24 months.
The primary endpoint was objective response rate (ORR), and the primary analysis occurred after a median follow-up of 10.9 months.
The mean age of the study population was 60 years, six patients had newly diagnosed stage III disease, 15 had newly diagnosed stage IV disease, and 24 had recurrent disease. Two-thirds of the cancers had endometrioid histology, and 80% were MMR efficient (PMMR).
In the efficacy-evaluable population, one patient had a complete response, 31 had a partial response, eight had stable disease, and one patient had progressive disease, resulting in an ORR of 78% and a disease control rate of 97.6%.
Median PFS, a secondary endpoint, was 17.77 months, and the 12-month PFS rate was 58.6% (85.7% in the dMMR subgroup). Median OS had yet to be reached, but 12-month OS was 88.1% and did not differ between the dMMR and pmMR subgroups (85.7% and 89.0%, respectively).
Eight of 45 patients had grade 3/4 TRAEs, and no grade 5 TRAEs occurred. Grade 3/4 rash and allergy each occurred in two patients, and grade 3/4 adrenal insufficiency, hyperglycemia, myelosuppression, and hypokalemia each occurred in one patient.
