Tukysa (tucatinib)

P2, N=36, Recruiting, SCRI Development Innovations, LLC | Trial completion date: Jul 2026 --> Nov 2027 | Trial primary completion date: Jul 2026 --> Nov 2027

These data support systemic therapy as an approach in HER2+ breast cancer LM. ClinicalTrials.gov registration: NCT03501979 .

P1/2, N=40, Active, not recruiting, Criterium, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Aug 2024 --> Mar 2026

Tucatinib significantly decreases intratumoral proliferation and hypoxia in both cell-line and patient-derived xenograft models of HER2 + breast cancer, which can be longitudinally quantified with PET imaging. Our data suggests molecular imaging may improve understanding and prediction of tucatinib response.

P=N/A, N=26, Not yet recruiting, Duke University | Initiation date: Jan 2026 --> Apr 2026

Tucatinib plus trastuzumab was cost-effective if its price was the same as lapatinib for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic CRC from the perspective of healthcare payers in China. Our exploratory result could provide a reference for clinical application of tucatinib plus trastuzumab when they are correctly interpreted.

P2, N=720, Recruiting, Canadian Cancer Trials Group | Trial primary completion date: Jan 2026 --> Dec 2026

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial primary completion date: Jun 2026 --> Jul 2027

The value of HER2-targeted treatments in patients with HER2+ mCRC has been evidenced by clinical trials and meta-analyses, with strong evidence from MOUNTAINEER and DESTINY-CRC01 which supports the use of tucatinib + trastuzumab or trastuzumab deruxtecan, respectively, among this patient population. Strong evidence and clinical guidelines support the value of HER2-targeted treatment among patients with HER2+ mCRC. There is a need for increased awareness and earlier uptake of HER2 testing among patients with mCRC to broaden treatment options and optimise outcomes for this patient population.

Key 2025 findings (50 clinical trials) include: (1) confirmation of overall survival benefit with adjuvant CDK4/6 inhibitors in HR+/HER2- early breast cancer (monarchE: HR = 0.842, p = 0.0273); (2) establishment of trastuzumab deruxtecan (T-DXd) as a new standard in high-risk HER2+ early disease (DESTINY-Breast05: IDFS HR = 0.47) and first-line metastatic settings (DESTINY-Breast09: PFS HR = 0.58); (3) validation of TROP2-directed ADCs as first-line therapy for metastatic triple-negative breast cancer (ASCENT-03: PFS HR = 0.62; BEGONIA: ORR 79%); (4) paradigm shift to proactive, liquid biopsy-guided therapy switching (SERENA-6: PFS HR = 0.44); (5) updated efficacy and safety of the oral SERD imlunestrant from the EMBER-3 trial, supporting its role in ESR1-mutated advanced breast cancer and in combination with abemaciclib; (6) confirmation of long-term survival benefit for neoadjuvant carboplatin in early TNBC and new positive adjuvant data; (7) pivotal advances in HER2+ metastatic disease sequencing with tucatinib and T-DXd; (8) evidence supporting optimized adjuvant endocrine therapy in HER2+/HR+ early disease; and (9) emergence of novel agents with improved therapeutic indices, including PROTAC degraders, oral SERDs, and mutant-selective PI3K inhibitors. Unifying themes include biomarker-driven personalization, strategic treatment sequencing, management of unique toxicities, and emphasis on patient-reported outcomes. Future challenges include optimizing treatment integration, managing financial toxicity, and ensuring equitable global access.

P2, N=40, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Dec 2025 --> Dec 2026