Zongertinib combination therapy in HER2-positive metastatic breast cancer (mBC): First results from a phase Ib/II trial.
Rattachement africain : jp, it, cn, us, de, at. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
1044 Background: Zongertinib, an irreversible TKI, selectively inhibits HER2 while sparing wild-type EGFR, thereby minimizing associated toxicities. Beamion BCGC-1 (NCT06324357) is an ongoing Ph Ib/II multicohort trial investigating zongertinib as monotherapy or in combination with other agents in HER2-positive mBC, metastatic colorectal cancer, and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. Here, we report the first data from 4 Ph Ib cohorts evaluating zongertinib plus antibody-drug conjugates (ADCs) or trastuzumab-based therapy in patients (pts) with HER2-positive mBC, focusing on ADC combinations, as well as supporting preclinical data. Methods: Preclinical activity of zongertinib combinations was assessed in xenograft mouse models. Beamion BCGC-1 includes pts with confirmed, unresectable HER2-positive mBC who progressed following HER2-directed therapy. Pts received escalating doses of zongertinib plus fixed doses of T-DM1 (Cohort A; 3.6 mg/kg), T-DXd (Cohort B; 5.4 mg/kg), trastuzumab (Cohort K; 8 mg/kg loading dose followed by 6 mg/kg) or capecitabine (1000 mg/m 2 ) plus trastuzumab (Cohort G; 8 mg/kg loading dose followed by 6 mg/kg). The primary endpoint is the occurrence of DLTs during the MTD evaluation period. Secondary endpoints included further safety assessments and objective response (investigator-assessed; RECIST v1.1). Results: In xenograft mouse models, the addition of zongertinib to T-DM1 or T-DXd led to increased antitumor activity. As of November 4, 2025, 12 pts had been enrolled to Cohort A (median age: 58 years), 16 to Cohort B (median age: 58 years), 4 to Cohort G (median age: 48 years) and 7 to Cohort K (median age: 58 years). Most pts were heavily pretreated, with prior exposure to T-DXd, T-DM1 and/or TKIs. In Cohort A, treatment emergent adverse events (TEAEs) and zongertinib-related AEs (any grade [G]/G3) were reported in 12/5 (100%/42%) and 11/5 (92%/42%) pts, respectively. Three (25%) pts had AEs leading to zongertinib dose reduction. No pts had an AE leading to zongertinib discontinuation. The most common TEAEs (any G/G3) were increased AST (7/1 [58%/8%] pts), decreased platelet count (5/2 [42%/17%] pts) and increased ALT (5/1 [42%/8%] pts). In Cohort B, TEAEs and zongertinib-related AEs (any G/G3) were reported in 14/7 (88%/44%) and 14/5 (88%/31%) pts, respectively. Three (19%) pts had AEs leading to zongertinib dose reduction and 3 (19%) had AEs leading to zongertinib discontinuation. The most common TEAEs (any G/G3) were anemia (8/2 [50%/13%] pts), diarrhea (8/2 [50%/13%] pts) and nausea (8/1 [50%/6%] pts). No grade 4 or 5 TEAEs occurred in Cohorts A and B. Efficacy analyses are ongoing and will be presented. Conclusions: No new safety signals were observed with zongertinib plus T-DXd or T-DM1. Dose escalation was ongoing in Cohorts A and B at data cutoff. Clinical trial information: NCT06324357 .
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Zongertinib combination therapy in HER2-positive metastatic breast cancer (mBC): First results from a phase Ib/II trial.
- Date Crossref
- 01/06/2026
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Japanese Foundation For Cancer Research pays non établi dans la noticeOrganisation à but non lucratif
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Humanitas University IRCCS Humanitas Research Hospital pays non établi dans la noticeUniversité ou école supérieure
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IRCCS Humanitas Research Hospital pays non établi dans la noticeÉtablissement de santé
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Fudan University Shanghai Cancer Center pays non établi dans la noticeÉtablissement de santé
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Henan Cancer Hospital pays non établi dans la noticeÉtablissement de santé
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Harbin Medical University pays non établi dans la noticeUniversité ou école supérieure
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Third Affiliated Hospital of Harbin Medical University pays non établi dans la noticeÉtablissement de santé
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European Institute of Oncology pays non établi dans la noticeÉtablissement de santé
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University of California Chao Family Comprehensive Cancer Center pays non établi dans la noticeUniversité ou école supérieure
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Kyoto University pays non établi dans la noticeUniversité ou école supérieure
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Boehringer Ingelheim (Austria) pays non établi dans la noticeEntreprise
Japanese Foundation For Cancer Research, IRCCS Humanitas Research Hospital — Humanitas University et IRCCS Humanitas Research Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.