Near-Perfect Disease Control for Bispecific in Advanced Endometrial Cancer

SAN JUAN, Puerto Rico — Almost 100% of patients with recurrent/metastatic endometrial cancer benefited from an investigational bispecific antibody plus standard chemotherapy, according to a small preliminary study from China.

In 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 cohort had a median progression-free survival (PFS) of almost 18 months, and median overall survival (OS) had 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.

Fewer than 20% of patients had grade 3/4 treatment-related adverse events (TRAEs), with skin rash and allergy being most common, reported Yang Sun, MD, of the Clinical Oncology School of Fujian Medical University in China, at the Society of Gynecologic Oncology meeting.

“Cadonilimab, combined with standard chemotherapy, showed promising antitumor activity as a first-line treatment for advanced or recurrent endometrial cancer,” said Sun. “Moreover, the combination has a favorable and manageable safety profile. In the next step, our team will focus on potential biomarkers 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 KEYNOTE-B21. Bispecific antibodies offer a potential option for filling that space and perhaps eventually moving into earlier lines of treatment.

“It’s phenomenal to see a bispecific in this space,” 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 PD-L/L1 and CTLA-4 B7 connections of the antigen-presenting cell and T cells. Bispecific antibodies directly bridge T cells to tumor cells to target destruction, while immune checkpoint inhibitors release the brakes on existing T cells.”

Some questions remain to be answered and perhaps will be addressed in a publication, he continued. More than half of the patients in the trial had recurrent disease, which can have an impact on the subsequent risk of recurrence. No information was provided about prior radiation therapy which also can affect recurrence risk.

The study showed “excellent” safety data, which will encourage use of the bispecific and potentially help move it forward to earlier disease states, Corr added.

Sun reported findings from the primary analysis of the phase II, single-arm CARE trial. Investigators enrolled 47 patients, 45 of whom were included in data analysis, 17 with stage I disease and 28 with stage II. All patients received six to eight cycles cadonilimab plus carboplatin/paclitaxel chemotherapy. Patients with at least 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 study population had a median age of 60, six patients had newly diagnosed stage III disease, 15 had newly diagnosed stage IV, and 24 had recurrent disease. Two-thirds of the cancers had endometrioid histology, and 80% were MMR proficient (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 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 occurred in two patients each, and grade 3/4 adrenal insufficiency, hyperglycemia, myelosuppression, and hypokalemia occurred in one patient each.

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