Clinical Summary: 

• Design/Population: This phase 1/2 dose-escalation and expansion study evaluated trastuzumab pamirtecan, a HER2-targeted antibody-drug conjugate, in patients with previously treated HER2-expressing advanced or metastatic endometrial cancer.
• Key Outcomes: Median progression-free survival was 8 months and median overall survival was 15 months. Confirmed objective response rates were consistent across key subgroups, including prior immune checkpoint inhibitor exposure and number of prior therapies, with the highest response rate observed in HER2 IHC 3+ tumors (73.1%). Black/African American patients achieved an objective response rate of 56.5%.
• Clinical Relevance: These findings demonstrate meaningful activity of trastuzumab pamirtecan and support ongoing phase 3 evaluation of this HER2-targeted antibody-drug conjugate.

Kathleen Moore, MD, Fred and Pamela Buffett Cancer Center, Omaha, Nebraska, discusses updated efficacy and survival results from a phase 1/2 study evaluating trastuzumab pamirtecan in patients with previously treated HER2-expressing advanced endometrial cancer. 

Results demonstrated durable antitumor activity regardless of prior treatment history, with response rates remaining consistent across racial groups, prior lines of therapy, and prior immunotherapy exposure. The strongest activity was observed in HER2 IHC 3+ tumors, where response rates exceeded 70%, while median overall survival reached 15 months in this heavily pretreated population, supporting continued investigation in the ongoing phase 3 FERN-EC01 trial.

Dr Moore presented these results at the European Society for Medical Oncology (ESMO) Gynecological Cancers Congress in Copenhagen, Denmark. 

Transcript: 

My name is Dr Kathleen Moore, and I'm the deputy director and director of phase 1 clinical research at the Fred and Pamela Buffett Cancer Center in Omaha, Nebraska.

At the ESMO Gynecologic Cancer Meeting in Copenhagen, I will be presenting the results of trastuzumab pamirtecan (TPAM) in patients with previously treated HER2-expressing advanced endometrial cancer, specifically reporting on overall survival and progression-free survival from the phase 2 dose-expansion cohort. 

TPAM is a HER2-targeting antibody-drug conjugate with a topoisomerase I inhibitor payload. What I'm presenting is the results of a large expansion cohort from a phase 1/2 trial that initially was dose-escalation but then moved into dose expansion in patients with recurrent HER2-expressing endometrial cancer. Patients received TPAM at 8 mg/kg intravenously every 3 weeks.

The response rate was quite striking, with a response rate of 49% and this was among patients who had already received prior immune checkpoint inhibitor therapy, either as part of frontline metastatic therapy or in the recurrent setting as monotherapy or in combination with lenvatinib. In patients whose tumors were HER2 3+, the response rate was 70%.

This study was also notable because it did, in my opinion, a much better job of accruing a population that more accurately reflects the demographics of who is at risk for developing and dying from endometrial cancer. At least in the United States, this would represent our Black population. This study enrolled 17% Black or African American patients, which is one of the highest percentages of Black patients ever enrolled in a clinical trial of endometrial cancer, and really shows us that we can accomplish this when we open the right sites.  That being said, these patients also did incredibly well on this clinical trial. It is a subset of the entire population, but the response rate for Black or African American patients was 56.5%. Among those with HER2 3+ tumors, it was 73%. Again, we're very proud of our ability to accrue a more representative population than perhaps we've done in the past.

In terms of progression-free and overall survival, we do have to note that this is a single-arm study and there is no control arm. So we can't say these are statistically significant findings, but they are, I think, clinically informative. TPAM had a median progression-free survival of 8 months and a median overall survival of 15 months. Again, among patients who had sometimes had several lines of therapy already in the metastatic setting, we're still seeing these clinically relevant findings in terms of progression-free and overall survival.

From a safety standpoint, TPAM, like most topoisomerase I antibody-drug conjugates, was characterized by common but low-grade gastrointestinal toxicities, such as nausea, vomiting, and perhaps fatigue. The most common adverse event of special interest was pneumonitis, which was a composite term including either interstitial lung disease or pneumonitis. This was reported in 38 patients total, of whom 7 patients (5%) had a grade ≥3 event. So this is a key toxicity that we're watching for in this clinical trial.

In conclusion, TPAM showed encouraging antitumor activity in a large cohort of patients with previously treated HER2-expressing advanced endometrial cancer, with response rates approaching 50% or greater, a median progression-free survival of 8 months, and a median overall survival of 15 months.

While hypothesis-generating, the subgroup analysis of overall response rate showed consistent activity across key subgroups, including a confirmed overall response rate of almost 57% in Black or African American patients and 73% in patients with HER2 immunohistochemistry 3+ by local testing.

Pneumonitis is a clinically important adverse event, with implementation during the course of this clinical trial of more directed management strategies to reduce the risk of high-grade events. The safety profile of TPAM was manageable and consistent with other anti-HER2 antibody-drug conjugates.

There is a global, open-label, randomized phase 3 trial called FERN-EC01 that is now ongoing to evaluate TPAM versus investigator's choice chemotherapy in patients with previously treated HER2-expressing recurrent endometrial cancer. We look forward to seeing the results of that study.

Source: 

Moore K, Wu X, Makker V, et al. Trastuzumab pamirtecan (T-Pam/DB-1303/BNT323) in patients (pts) with previously treated, HER2-expressing, advanced endometrial cancer (EC): Overall survival (OS) and efficacy in pt subgroups of a phase II dose-expansion cohort. Presented at ESMO Gynecological Cancers Congress. June 17-19, 2026. Copenhagen, Denmark. Abstract 83RO.