Tukysa (tucatinib) / Pfizer - LARVOL DELTA

BRIDGET: Secondary BRain Metastases Prevention After Isolated Intracranial Progression on Trastuzumab/Pertuzumab or T-DM1 in Patients With aDvanced Human Epidermal Growth Factor Receptor 2+ brEast Cancer With the Addition of Tucatinib (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Carey Anders, M.D. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Real World-clinical Outcomes of Tucatinib, Trastuzumab, and Capecitabine Following Trastuzumab Deruxtecan (T-DXd) for the Treatment of HER2-positive Metastatic Breast Cancer. (clinicaltrials.gov) - P=N/A | N=93 | Active, not recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Effect of caprine herpes virus-1 (CpHV-1) on cell viability and chemosensitivity in breast cancer cells. (ASCO 2025) - "We also examined CpHV-1's combination with Abemaciclib (A), Tucatinib (T), and Inavolisib (I) using MTS assays and Chou-Talalay analysis The CpHV-1 infection showed a time and dose-dependent cytotoxic effect in all BC cells without significantly affecting the normal cells. CpHV-1 demonstrates potential as an effective therapeutic agent for cancer treatment, particularly when combined with standard targeted therapies. This combination enhances sensitivity in BC cells, including triple-negative subtypes. While further research is required to fully understand the mechanisms underlying CpHV-1's infection, our findings underscore the promise of these combined therapies as a novel and effective strategy for BC."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Enhanced efficacy of inavolisib combined with anti-PD-1 or anti-HER2 antibody in treating brain metastases from breast cancer. (ASCO 2025) - "Alpelisib is the only approved PI3K inhibitor for treating PIK3CA mutation-positive breast cancer...In addition to the Inavolisib monotherapy and vehicle control groups, Inavolisib was combined with a PD-1 antibody or albumin-bound paclitaxel in the triple-negative model...However, overall, the combination with trastuzumab achieved unexpectedly good results, which were comparable to SHR-A1811 and superior to Tucatinib... Our findings suggest that the combination of the PI3K inhibitor Inavolisib with anti-PD-1 or anti-HER2 antibody therapy may offer an effective strategy for treating brain metastases in breast cancer. This discovery provides new insights and possibilities for improving treatment options in breast cancer brain metastasis. Further research is needed to validate the efficacy and safety of this combination therapy."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • PIK3CA • PTEN

The current status of quinazoline hybrids with antibreast cancer therapeutic potential-part II. (PubMed, Future Med Chem) - "Moreover, several quinazoline hybrids, which are exemplified by tucatinib and lapatinib, have already been applied in clinics for the treatment of breast cancer, revealing that quinazoline hybrids are valuable entities for the exploitation of novel antibreast cancer chemotherapeutics. This review outlines the current status of quinazoline hybrids with antibreast cancer potential, covering articles published from 2020 onwards. The structure-activity relationships (SARs) and mechanisms of action are also discussed to provide a potential avenue for developing more effective antibreast cancer candidates."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

TUGETHER: Tucatinib Together With Pembrolizumab and Trastuzumab (clinicaltrials.gov) - P2 | N=31 | Terminated | Sponsor: Breast Cancer Trials, Australia and New Zealand | N=57 ➔ 31 | Trial completion date: Sep 2026 ➔ Jun 2025 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Jun 2025; Stopped on the recommendation of the BCT Independent Data and Monitoring Committee

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

The impact of ethnicity on benefit from novel drugs approved for breast cancer treatment: a systematic review and meta-analysis of randomized phase 3 trials of the last decade. (SABCS 2024) - "23 phase III RCTs were identified in the aBC setting, with 1547 (11.1%) patients of Asian ethnicity. Experimental drugs tested included CDK4/6i (palbociclib, ribociclib, abemaciclib), SERD (elacestrant), PI3Ki (alpelisib), PARPi (olaparib, talazoparib), broad variety of anti-HER2 drugs (tucatinib, trastuzumab deruxtecan, pertuzumab, T-DM1, neratinib, margetuximab), anti-PD-1 and anti-PD-L1 drugs (pembrolizumab, atezolizumab) and anti-TROP2 drug (sacituzumab govitecan). 16 RCTs provided HR (95%CI) for PFS in the subgroup of Asians and 17 RCTs for Non-Asians."

IO biomarker • P3 data • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Biomarker testing in metastatic colorectal cancer (mCRC): 2015-2024 trends in the United States (US) community oncology setting. (ASCO 2025) - "In 2020, following the approval of tucatinib, HER2 testing rates increased from 32%-66% prior to 2019 to 89%-93% after 2020. BRAF testing rates also increased to 90%-96% after 2017, following the approval of encorafenib plus cetuximab combination therapy for BRAF-mutated mCRC in 2018. NTRK testing rates (21%-42%) showed improvement over the study period, with the highest proportion of patients tested in 2024 corresponding to the accelerated approval of repotrectinib for in the same year. Similarly, RET testing (25%-89%) peaked in 2023 following breakthrough therapy designation for selpercatinib in late 2022... As new targeted therapies have emerged in recent years, biomarker testing rates for mCRC have rapidly increased in the community oncology setting. NTRK or RET rearrangements are infrequent in advanced CRC, with lower testing rates for these genes within the study period. However, as this study leveraged structured data only, actual rates of testing may be even..."

Biomarker • Metastases • Colorectal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS • NTRK

Real-world treatment patterns and outcomes in HER2-positive metastatic breast cancer patients with brain metastases. (ASCO 2025) - "First line systemic therapy for HER2+ MBC is trastuzumab (H), pertuzumab (P) and Taxol (T). Subsequent therapies include trastuzumab emtansine (T-DM1), tucatinib/H/capecitabine triplet therapy (TUC) and trastuzumab deruxtecan (T-DXd)... TUC and T-DXd are increasingly prescribed as initial systemic treatment after BM diagnosis. The combination of SRS and HER2 targeted therapies in this cohort resulted in excellent survival outcomes with limited risk of RN. Future studies and longer follow-up will allow for a better understanding of how treatment patterns affect survival outcomes and patient quality of life."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Predictors of overall survival in patients with brain metastases from HER2+ breast cancer. (ASCO 2025) - "Significant features associated with increased mortality risk in the Combined model included a higher RS, absence of tucatinib treatment for the primary BC prior to BM development, elevated Ki-67 expression, Black race, higher N stage, and brainstem metastases... A distinct RS from brain MRI is the strongest predictor of OS in patients with BM from HER2-positive BC, surpassing clinical factors. RS may refine risk stratification and guide treatment or clinical trial prioritization."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy of systemic therapy in breast cancer with CNS metastases: "Real-world" experience. (ASCO 2025) - "Tucatinib-based regimens showed a 100% DCR with median PFS of six months. Other therapies, including sacituzumab, abemaciclib, and trastuzumab-emtansine, showed stable disease as the best response... This "real-world" experience highlights that, at our institution, most patients with breast cancer and CNS metastases considered for upfront systemic therapy lack measurable disease (91% having lesions < 10 mm) typically required for clinical trials. Nonetheless, the response rate aligns with published experiences. In addition, we included patients with LMD, who are often excluded in trials."

Clinical • Real-world • Real-world evidence • Breast Cancer • CNS Tumor • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Efficacy of tucatinib, trastuzumab, and capecitabine (TTC) following trastuzumab-deruxtecan (T-DXd) in HER2-positive metastatic breast cancer (MBC): Updated results and subgroup analyses from the UNICANCER multicenter retrospective cohort. (ASCO 2025) - "Patients had received a median of 4 prior MBC therapies (range: 2–15), which included pertuzumab (81%) and T-DM1 (93%). This large retrospective cohort with extended follow-up highlights the efficacy of TTC in HER2-positive MBC patients previously treated with T-DXd. These findings support the role of TTC as a viable treatment option post-T-DXd and provide insights for optimizing therapeutic strategies in this setting."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Zongertinib in HER2-altered breast cancer: Preclinical activity and preliminary results from a phase Ia dose-escalation study. (ASCO 2025) - P1 | " Cell proliferation assays were undertaken in HER2-amplified BC cell lines (relative copy numbers ranging from 3.2–10.1) exposed to serial dilutions of zongertinib and tucatinib. Zongertinib potently inhibits HER2-driven BC growth in preclinical models in vitro and in vivo. Preliminary Ph Ia data indicate that zongertinib has encouraging clinical activity and manageable safety in pts with advanced, HER2-driven BC."

P1 data • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Accelerating phase 2 clinical development with real-world data (RWD): An external control arm (ECA) pilot in HER2-positive (HER2+) metastatic breast cancer (mBC). (ASCO 2025) - "To explore this potential, we piloted the development of a contemporaneous ECA for a newly launched Ph 2 trial of Tucatinib and Doxil in HER2+ mBC (NCT0578834)...Propensity scores (PSs) were estimated using logistic regression with covariates selected based on literature and expert input (age at index, number of prior treatments, prior fam-trastuzumab deruxtecan-nxki (Enhertu), and prior tucatinib)... This pilot demonstrates that RWD can be quickly and efficiently assembled in pace with an ongoing Ph 2 clinical trial, offering promise for accelerated decision-making in clinical drug development. When small sample sizes in Ph 2 trials pose challenges, this approach shows that an exchangeable ECA can be achieved as trial accrual progresses, providing a framework for ECA evidence generation."

Clinical • Metastases • P2 data • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

HER2CLIMB-05: A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer (clinicaltrials.gov) - P3 | N=654 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial primary completion date: May 2025 ➔ Feb 2026

Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A Study to Learn More About Tukysa Once it is Out in the Korean Market (clinicaltrials.gov) - P=N/A | N=600 | Not yet recruiting | Sponsor: Pfizer | Initiation date: Mar 2025 ➔ Dec 2026

Trial initiation date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (clinicaltrials.gov) - P2 | N=4200 | Recruiting | Sponsor: American Society of Clinical Oncology | Trial completion date: Jun 2027 ➔ Dec 2028 | Trial primary completion date: Jun 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Tumor mutational burden • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BRAF

HER2-Positive Breast Cancer-Current Treatment Management and New Therapeutic Methods for Brain Metastasis. (PubMed, Biomedicines) - " The standard treatment is based on trastuzumab plus pertuzumab in combination with taxane chemotherapy... Through the years, many advanced therapies have been introduced to treat brain metastases, including whole brain radiotherapy, stereotactic radiosurgery, and a tyrosine kinase inhibitor (TKI), neratinib. Nonetheless, this still remains a therapeutic challenge. In this review, we focus on the treatment and efficiency of therapies targeting HER2-positive breast cancer, mainly concentrating on the current and newly developed treatment options for brain metastases, such as trastuzumab deruxtecan and tucatinib."

Journal • Review • Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

EmpowHER-303: A phase 3 study of zanidatamab vs trastuzumab with physician's choice of chemotherapy in patients with HER2+ metastatic breast cancer whose disease progressed on trastuzumab deruxtecan (AACR 2025) - P3 | "Based on physician's choice, pts' eligibility, and institutional/local guidelines, pts may have received post-T-DXd therapy (eg, a tucatinib-based regimen and/or trastuzumab emtansine). Pts must be eligible to receive the physician's choice of chemotherapy (eribulin, gemcitabine, vinorelbine, or capecitabine)...The primary endpoint is progression-free survival (PFS) by blinded independent central review; overall survival is the key secondary endpoint. Other secondary endpoints include confirmed objective response rate, duration of response, investigator-assessed PFS, safety, and pt-reported outcomes."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Early Access Program in oncology: Retrospective study at a Portuguese hospital (ECOP 2024) - "During the study period were submitted 163 EAP requests for abiraterone, amivantamab, bevacizumab, durvalumab, encorafenib, enfortumab, everolimus, erdafitinib, lenvatinib, lurbinectedin, niraparib, nivolumab, olaparib, pembrolizumab, pertuzumab, ramucirumab, sacituzumab govitecan, selpercatinib, trifluridine/tipiracil, trametinib+dabrafenib, trastuzumab-deruxtecan and tucatinib. Conclusion Most cases correspond to metastatic disease, EAPs facilitate timely access to innovative therapies for patients with high unmet medical needs. The majority of situations were financed, which confirms the importance of EAPs in an era where oncology is constantly innovating."

Retrospective data • Gastrointestinal Disorder • Oncology

Real-World Outcomes for HER2-Positive MBC: Exploring Global Perspectives and Regional Differences in Treatment Approaches (GBCC 2025) - "Real-World Data on Recently Approved Agents and HER2-Targeting Biosimilars Recent clinical trials have introduced several promising treatment options for HER2-positive MBC, including T-DXd, tucatinib, and T-DM1. Beyond their clinical trial efficacy, real-world studies support their effectiveness and tolerability in broader patient populations. Additionally, HER2-targeting biosimilars (e.g., Ontruzant, Herzuma) have gained widespread acceptance globally, and real-world evidence supports their comparable efficacy and safety in managing HER2-positive breast cancer."

Clinical • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Advances in Targeted Therapy for Brain Metastases in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer: A Focus on ADCs and TKIs. (PubMed, Breast Cancer (Dove Med Press)) - "Key therapies, including trastuzumab deruxtecan (T-DXd) and tucatinib, are discussed, with a focus on their mechanisms, efficacy, and ability to overcome the blood-brain barrier (BBB). Future research should focus on optimizing combination therapies, exploring novel biomarkers, and addressing resistance mechanisms to further improve outcomes. This review underscores the importance of continued innovation in targeted therapies for brain metastasis."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

VRN101099: A novel treatment option for HER2-driven cancer patients, overcoming T-DXd resistance and brain metastases (AACR 2025) - "In intracranial xenograft models, VRN101099 demonstrated superior anti-tumor efficacy to tucatinib, neratinib, zongertinib, trastuzumab, and T-DXd. In conclusion, VRN101099 is a promising HER2-selective TKI with a favorable profile including potency, tolerability, and brain permeability. This identifies VRN101099 as a potential novel systemic treatment option for patients with HER2-driven cancers, particularly those with brain metastases or those who have progressed after or failed with T-DXd."

Clinical • Late-breaking abstract • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

Safety and Efficacy of Anti-Human Epidermal Growth Factor 2 Agents in the Treatment of Biliary Tract Cancers: A Systematic Review. (PubMed, JCO Precis Oncol) - "In patients with HER2-expressing BTCs, anti-HER2 therapies are viable options, particularly in the second-line setting."

Journal • Review • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

Zanidatamab (Zani) + chemotherapy (Chemo) for patients (Pts) with HER2-expressing metastatic breast cancer (mBC): Final results of a phase I trial (ESMO-BC 2025) - P1 | "We report the final analysis of a phase I trial of zani + chemo in pts with HER2-expressing mBC. Part 3 of the phase I trial (NCT02892123) evaluated zani + chemo (paclitaxel [pac], capecitabine [cap] or vinorelbine [vin]) or zani + cap + tucatinib (tuc) in pts with HER2-expressing mBC...Prior (>5% of pts) anti-HER2 therapies included trastuzumab (93%), T-DM1 (91%), pertuzumab (80%), lapatinib (24%), T-DXd (9%), tuc (9%), and neratinib (7%)... Zani + chemo had a manageable safety profile and good tolerability with promising antitumour activity and durable responses in heavily pretreated pts with HER2-expressing mBC. Among pts with HER2+ mBC with prior HER2-targeted regimens, adding zani to chemo showed encouraging PFS."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2