Phase 3 data showed a significant PFS improvement with trastuzumab pamirtecan vs chemotherapy in HR-positive, HER2-low metastatic breast cancer.
Trastuzumab pamirtecan (BNT323/DB-1303) delivered a statistically significant yet modest progression-free survival (PFS) improvement compared with investigator’s choice of single-agent chemotherapy in patients with hormone receptor (HR)–positive, HER2-low metastatic breast cancer, meeting the primary end point of the randomized, open-label phase 3 DYNASTY-Breast02 trial (NCT06018337).¹
Notably, 541 patients were enrolled in the trial. Data for overall survival (OS), a secondary end point, were not mature at the time of this current interim analysis.1,2
Interstitial lung disease (ILD) occurred at a higher rate in this trial than in earlier trials of the agent, with most cases being grade 1 or 2, and grade 3 to 5 (severe or fatal) ILD events were reported in a small proportion of patients.1 The remainder of the safety data in this trial were consistent with the safety data seen in earlier trials with trastuzumab pamirtecan, and no new safety signals were observed, BioNTech and DualityBio, the developers of trastuzumab pamirtecan, stated in a news release.
In the news release, the companies also stated that the available data suggest that the potential benefit with this agent will be limited to the HR-positive, HER2-low breast cancer setting, and that they will determine next steps for developing the agent.
Trastuzumab Pamirtecan in HR-positive, HER2-Low Metastatic Breast Cancer: DYNASTY-Breast02 Highlights
Trastuzumab pamirtecan is a third-generation antibody-drug conjugate (ADC) that targets HER2 with a topoisomerase I inhibitor–based design. The DYNASTY-Breast02 trial enrolled patients with HER2-low disease, defined as immunohistochemistry (IHC) 2+ with negative in situ hybridization (ISH) or IHC 1+, who were randomly assigned 1:1 to receive trastuzumab pamirtecan or investigator’s choice of single-agent capecitabine, paclitaxel, or nab-paclitaxel (Abraxane).² Patients continued to receive treatment until RECIST 1.1 criteria–defined progression, intolerable adverse effects, consent withdrawal, or another protocol-specified reason to stop.
Patients qualified for enrollment on the trial if they were at least 18 years of age and had pathologically documented advanced or metastatic HER2-low, HR-positive breast cancer that was never previously reported as HER2-positive (defined as IHC3+ or ISH+). Their disease must have progressed after at least 2 prior lines of endocrine therapy, or within 6 months of starting first-line endocrine therapy plus a CDK4/6 inhibitor for metastatic disease; had an ECOG performance status of 0 or 1; had received no prior chemotherapy for advanced or metastatic disease; had a life expectancy of at least 12 weeks at screening; had at least 1 measurable lesion per RECIST 1.1 criteria; had a left ventricular ejection fraction of at least 50% within 28 days of random assignment; had adequate organ and bone marrow function within 14 days before random assignment; and had undergone an adequate treatment washout period before random assignment. Patients were also required to have an adequate tumor tissue sample available for central HER2 assessment, preferably obtained at or after the identification of metastatic disease.
Patients were excluded from enrollment if they had received prior anti-HER2 therapy, had prior exposure to an ADC with an exatecan-derivative topoisomerase I inhibitor payload, or had a history of ILD.
The primary end point was PFS by blinded independent central review per RECIST 1.1 criteria in the HR-positive, HER2-low population. Secondary end points included OS, objective response rate, duration of response, investigator-assessed PFS, safety, and patient-reported outcomes.
Trastuzumab pamirtecan is also being evaluated in the randomized phase 3 Fern-EC-01 trial (NCT06340568) in patients with previously treated, HER2-expressing advanced or recurrent endometrial cancer and in a global phase 1/2 trial (NCT05150691) in patients with advanced or metastatic solid tumors.1
