Tukysa (tucatinib)

A number of BM treatment-effective drugs have shown BM-preventive effects: In NSCLC, the EGFR-inhibitor osimertinib and ALK inhibitors like alectinib, brigatinib and lorlatinib lower the incidence of BM. In HER2-positive breast cancer, tucatinib and trastuzumab deruxtecan have preventive activity in patients without BM at baseline...Preventing BM requires a personalized, multidisciplinary approach, integrating tumor biology, individual risk assessment, and therapeutic advances. Secondary prevention in patients with BM is as vital as tertiary prevention, warranting prospective validation of preclinical concepts.

P1/2, N=24, Not yet recruiting, MedSIR

Trastuzumab deruxtecan demonstrates substantial antitumor activity through potent cytotoxic effects and a bystander effect, supporting its efficacy in tumors with intratumoral heterogeneity or downstream pathway activation. In contrast, tucatinib-based regimens represent an important option for patients with brain metastases and tumors expressing p95HER2. The ongoing development of novel antibody-drug conjugates and bispecific antibodies is expected to further advance personalized sequential therapy targeting composite resistance mechanisms.

Trastuzumab-based combinations and HER2-selective tyrosine kinase inhibitors such as tucatinib have demonstrated durable responses and favorable safety profiles in heavily pretreated patients. This review summarizes current evidence from pivotal phase II and III clinical trials, translational studies, and real-world data evaluating EGFR-, BRAF-, and HER2-directed therapies in colorectal cancer. Particular emphasis is placed on biomarker-guided patient selection, mechanisms of resistance, and emerging combination strategies that continue to refine precision oncology approaches in mCRC.

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