Trastuzumab pamirtecan (T-Pam) — a third-generation HER2-targeted antibody-drug conjugate — has substantial and durable antitumor activity in patients with previously treated HER2-expressing advanced or recurrent endometrial cancer, according to a phase 2 study.

The study of 145 patients found that nearly half of those who had progressed after prior platinum and immune checkpoint inhibitor (ICI) therapy achieved an objective response on T-Pam, with responses lasting a median of about 10 months.

Responses were observed across all HER2 immunohistochemistry (IHC) scores but were most pronounced among patients with IHC scores of 3+, whose objective response rate topped 70%.

Bhavana Pothuri, MD, gynecologic oncologist at NYU Langone in New York City, reported the results at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer 2026.

“These are phenomenal outcomes to see,” said study discussant Bradley Corr, MD, gynecologist oncologist with UCHealth Cancer Care in Aurora, Colorado.

“The response rates are exceptional across the board but better with higher HER2 expression, an important detail to help us communicate with our patients in regard to expected outcomes,” Corr said.

Breakthrough Therapy

Recurrent endometrial cancer continues to represent a high unmet need, with limited second-line options after first-line systemic therapy. HER2 overexpression, Pothuri said, is common in endometrial cancer, and T-Pam has demonstrated promising efficacy in patients with HER2-expressing disease.

In December 2023, the antibody-drug conjugate received FDA breakthrough therapy designation for the treatment of patients with advanced endometrial cancer who progressed during or after ICI therapy.

Pothuri presented primary results from cohort 2b of an open-label phase 2 study of T-Pam in 145 patients with advanced, recurrent, or metastatic HER2-expressing endometrial cancer. Treatment consisted of T-Pam 8 mg/kg every 3 weeks until confirmed progressive disease, withdrawal of consent, loss to follow-up, death, or end of study.

All patients had received prior chemotherapy, 76% had received ICI therapy, and 21% had been treated with a prior anti-HER2 regimen.

The study met its primary efficacy endpoint, with a confirmed objective response rate of 49.3% in 73 evaluable patients previously treated with ICI therapy and confirmed HER2 status by central testing. Among all centrally tested patients (n = 96), the objective response rate was 47.9%. Median progression-free survival was 6.8 months and 8.1 months, respectively.

Among all 143 evaluable patients by local HER2 testing, the confirmed objective response rate was 44.1%, with a median progression-free survival of 8 months. Outcomes were similar for the 109 evaluable patients who’d received prior ICI therapy (objective response rate, 45.9%; median progression-free survival, 8 months).

T-Pam consistently demonstrated “encouraging” antitumor activity across all HER2 expression levels, Pothuri reported, with comparable results regardless of whether testing was done locally or centrally. With central testing, objective response rates were 34.5% for patients with IHC 1+, 44.2% for those with IHC 2+, and 70.8% for those with IHC 3+. With local testing, the corresponding rates were 33.9%, 40.4%, and 73.1%, respectively.

Among all patients, the median duration of response was 11.1 months by central testing and 10.3 months by local testing, with disease control rates of 83.3% and 81.8%, respectively.

Safety Findings

The drug’s safety profile, Pothuri said, was as expected for HER2-targeted antibody-drug conjugates. Most patients experienced at least one treatment-related adverse event, most commonly low-grade nausea, anemia, platelet count decrease, and low-grade fatigue.

Grade 3 or higher treatment-related events occurred in 68 of 145 patients (47%), leading to dose reductions in 33 patients (23%), drug interruption in 39 patients (27%), and treatment discontinuation in 42 patients (29%).

Adverse events of special interest included infusion-related reactions, cardiac dysfunction, and interstitial lung disease (ILD) or pneumonitis. There were no grade 3 or higher infusion-related reactions, and one patient developed a left ventricular ejection fraction decrease of grade 3.

Adjudicated ILD or pneumonitis was observed in 38 patients, with seven patients (4.8%) experiencing a grade 3 or higher event. Three patients died due to treatment-related pneumonitis or acute respiratory failure.

“As we gained clinical experience with T-Pam,” Pothuri said, “additional monitoring and management strategies for ILD pneumonitis were implemented in a clinical trial protocol amendment, which aimed to reduce the risk of high-grade events.”

It’s “notable,” she added, that there were no fatal events after the amendment.

A global phase 3 randomized trial, Fern-EC-01, is underway to evaluate T-Pam monotherapy (vs the investigator’s choice of chemotherapy) in previously treated patients with HER2-expressing, recurrent endometrial cancer.

T-Pam is being jointly developed by BioNTech and DualityBio. The companies plan to file a biologics license application in 2026, subject to regulatory feedback from the FDA.

The study was sponsored by DualityBio and conducted in collaboration with BioNTech. Pothuri reported receiving research funding (to the institution) from DualityBio and consulting for BioNTech. Corr reported serving as an advisor to BioNTech, GSK, Gilead Sciences, and other companies.