Tukysa (tucatinib) / Pfizer - LARVOL DELTA

Systemic vs. local treatment in active breast cancer brain metastasis: Local treatment (EANO 2026) - "The emergence of CNS-active systemic therapies, tucatinib and trastuzumab deruxtecan, has prompted debate over whether local treatment remains necessary for active breast cancer brain metastases. Modern systemic therapy should change how we select and sequence local treatment, not make it obsolete. The optimal approach is integration: local therapy for urgent or symptomatic disease, systemic therapy for asymptomatic small-volume disease, and close surveillance with local salvage at progression."

Breast Cancer • Hematological Malignancies • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Development in systemic therapies in BM (EANO 2026) - "In EGFR- and ALK-driven lung cancer, third-generation tyrosine kinase inhibitors and novel combinations (e.g. osimertinib-based regimens, amivantamab plus lazertinib, lorlatinib) have shown high intracranial response rates and durable CNS control, with newer trials such as ESAONA now defining eligibility around BM rather than treating it as a subgroup. In HER2-positive breast cancer, tucatinib-based combinations and trastuzumab deruxtecan similarly demonstrate that active, previously untreated BM can be prospectively studied and effectively treated, exemplified by the HER2CLIMB and DESTINY-Breast12 trials...Recent work by Le Rhun and colleagues applying pharmacoscopy to brain metastases from NSCLC has demonstrated feasibility and uncovered unexpected drug sensitivities, and this concept is now being advanced into prospective clinical evaluation. Such functional precision-oncology approaches may help close the therapeutic gap for the majority of BM patients who currently..."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • HER-2

MOUNTAINEER-03: Phase 3 study of tucatinib, trastuzumab, and modified FOLFOX6 as first line treatment in HER2+ metastatic colorectal cancer. (ASCO 2023) - P2, P3 | "Approximately 400 patients will be randomized 1:1 to the TUC experimental arm (TUC [300 mg orally twice daily] + Tras + mFOLFOX) or the SOC arm (mFOLFOX alone or in combination with either bevacizumab or cetuximab)...Enrollment is ongoing in North America, Asia, Australia, and Europe. Clinical trial information: NCT05253651."

Clinical • Metastases • P3 data • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • BRAF • HER-2

Biomarker-Guided Treatment Selection in Metastatic Colorectal Cancer: A Critical Review of Established and Emerging Therapies. (PubMed, Crit Rev Oncol Hematol) - "In dMMR/MSI-H mCRC, immune checkpoint inhibition is the established first-line standard, with pembrolizumab and nivolumab plus ipilimumab producing durable disease control...For BRAF V600E-mutant disease, encorafenib plus cetuximab with fluoropyrimidine-based chemotherapy is a first-line standard. HER2-directed therapy with tucatinib plus trastuzumab or trastuzumab deruxtecan and combined KRAS G12C and EGFR inhibition are established after prior treatment but are not approved in the first-line setting...In previously treated non-MSI-H/dMMR mCRC, STELLAR-303 was the first phase 3 trial to demonstrate a significant overall survival benefit with an immune checkpoint inhibitor-containing regimen, zanzalintinib plus atezolizumab. Other investigational strategies include additional immunotherapy combinations, EGFR-MET bispecific antibody therapy with amivantamab, T-cell-engaging bispecific antibodies, therapeutic cancer vaccines, cellular therapies, and microbiome-directed..."

Biomarker • IO biomarker • Journal • Review • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • KRAS • MSI • NTRK • RET

MOUNTAINEER-03: Phase 3 study of tucatinib, trastuzumab, and mFOLFOX6 as first-line treatment in HER2+ metastatic colorectal cancer—Trial in progress. (ASCO-GI 2023) - P2, P3 | "Approximately 400 pts will be randomized 1:1 to the TUC experimental arm (TUC [300 mg PO BID] + Tras + mFOLFOX) or the SOC arm (mFOLFOX alone or in combo w/ either bevacizumab or cetuximab)...Enrollment is ongoing in the US, w/ global sites planned. Clinical trial information: NCT05253651."

Clinical • Metastases • P3 data • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • HER-2

MOUNTAINEER-03 phase III study design: first-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer. (PubMed, Future Oncol) - P3 | "The MOUNTAINEER-03 phase III trial is designed to investigate the efficacy and safety of first-line tucatinib in combination with trastuzumab and modified FOLFOX6 (mFOLFOX6) versus standard of care (mFOLFOX6 plus bevacizumab or cetuximab) in patients with untreated HER2+, RAS WT locally advanced unresectable or mCRC...Key secondary endpoints are overall survival and confirmed objective response rate (according to RECIST v1.1 per BICR). Safety assessments will include surveillance and recording of adverse events, physical examination findings, vital signs, cardiac assessments, Eastern Cooperative Oncology Group performance status, concomitant medications, and laboratory tests.Clinical trial registration: NCT05253651 (ClinicalTrials.gov)."

Journal • P3 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS

Her2climb-05: a randomized, double-blind, phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as maintenance therapy for her2+ metastatic breast cancer (SABCS 2025) - P3 | "In the HER2CLIMB-05 trial, the addition of tucatinib to TRAS + PERT as 1L maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in PFS with a manageable safety profile in patients with HER2+ MBC."

Clinical • Combination therapy • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • HER-2

Active-comparator pharmacovigilance of tucatinib using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) (ESMO 2026) - No abstract available

Adverse events • Oncology

BREnnA: Phase II/III randomised study of ZN-A-1041 or tucatinib (TUC), in combination with trastuzumab + capecitabine (HX), in patients (pts) with HER2-positive locally advanced or metastatic breast cancer (HER2+ LA/mBC) with or without central nervous system (CNS) metastases (ESMO 2026) - No abstract available

Clinical • Combination therapy • Metastases • P2/3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

BRIDGET: A Phase II trial of tucatinib added to trastuzumab/pertuzumab or ado-trastuzumab emtansine after isolated intracranial progression in patients with advanced HER2-positive breast cancer (ESMO 2026) - No abstract available

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

Health-Related Quality of Life from HER2CLIMB-05: A Phase 3 Study of Tucatinib Versus Placebo in Combination with Trastuzumab and Pertuzumab as 1L Maintenance Therapy for HER2+ mBC (ESMO 2026) - No abstract available

Clinical • Combination therapy • HEOR • P3 data • HER2 Positive Breast Cancer • Oncology • HER-2

Comprehensive Evaluation of the Efficacy and Safety of HER2-Targeted Therapies in Biliary Tract Cancer: Systematic Review and Network Meta-Analysis (ACG 2026) - "A total of twelve early-phase clinical trials involving 400 patients with biliary tract cancer were included in the analysis. Across the available HER2-directed regimens, trastuzumab plus chemotherapy was evaluated in 2 trials (124 patients) and demonstrated an ORR of 43.2% (95% CI 19.4â68.8) with a DCR of 80.0% (95% CI 72.3â86.7). Trastuzumab plus pertuzumab, assessed in 2 trials (45 patients), showed an ORR of 20.9% (95% CI 9.1â35.3) and a DCR of 53.4% (95% CI 37.8â68.8)."

Retrospective data • Review • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

PRE-I-SPY-PI: PRE-ISPY Phase I/II Oncology Platform Program (clinicaltrials.gov) - P1/2 | N=280 | Recruiting | Sponsor: QuantumLeap Healthcare Collaborative | Phase classification: P1 ➔ P1/2 | N=124 ➔ 280 | Trial completion date: Dec 2029 ➔ Dec 2031 | Trial primary completion date: Dec 2028 ➔ Dec 2030

Biomarker • Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • Cholangiocarcinoma • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

Neoadjuvant trastuzumab, pertuzumab and tucatinib without chemotherapy in HER2+ early breast cancer: The TRAIN-4 study (ESMO-BC 2026) - "Patients with ≥65% FTV reduction continued treatment for six more cycles, while those with <65% reduction switched to standard chemotherapy with paclitaxel, carboplatin, trastuzumab, and pertuzumab for six cycles. A neoadjuvant regimen of trastuzumab, pertuzumab and tucatinib resulted in high pCR rates and favourable tolerability in stage II-IIIA HER2+ breast cancer, establishing proof of concept for chemotherapy-free triple HER2 blockade in HER2+ early breast cancer."

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

Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. (PubMed, J Clin Oncol) - P2 | "Tucatinib combined with trastuzumab had clinically significant antitumor activity and was well tolerated in patients with previously treated HER2+ mBTC."

Journal • Metastases • P2 data • Pan tumor • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • HER-2

Impact of baseline molecular alterations on the efficacy of tucatinib (TUC) plus trastuzumab (Tras) for HER2+, RAS WT metastatic CRC (mCRC) in MOUNTAINEER (ESMO 2023) - P2 | "Conclusions This exploratory analysis of the MOUNTAINEER trial found generally consistent clinical efficacy of TUC + Tras to the primary analysis across subsets of pts w/ HER2+ RAS-WT mCRC and other clinically relevant genomic alterations. Table: 551O cORR DOR n % 95% CI n Months 95% CI Mutations Tissue NGS 45 46.7 31.7 – 62.1 21 15.3 8.9 – 25.5 ERBB2 6 66.7 22.3 – 95.7 - APC 36 44.4 27.9 – 61.9 16 16.6 6.1 – NE TP53 40 45.0 29.3 – 61.5 18 16.6 8.9 – NE ctDNA NGS 66 39.4 27.6 – 52.2 26 12.4 8.3 – 20.5 PIK3CA 7 28.6 3.7 – 71.0 - ERBB2 15 46.7 21.3 – 73.4 7 11.4 6.1 – NE APC 37 45.9 29.5 – 63.1 17 15.3 6.2 – NE Amplifications Tissue NGS 45 46.7 31.7 – 62.1 21 15.3 8.9 – 25.5 ERBB2 44 47.7 32.5 – 63.3 21 15.3 8.9 – 25.5 BRCA2 5 80.0 28.4 – 99.5 - ctDNA NGS 66 39.4 27.6 – 52.2 26 12.4 8.3 – 20.5 BRAF 7 14.3 0.4 – 57.9 - CCND1 7 14.3 0.4 – 57.9 - CDK6 10 30.0 6.7 – 65.2 - EGFR 19 36.8 16.3 – 61.6 7 12.5 4.2 – NE ERBB2 57 40.4 27.6 – 54.2 23 12.4 6.2 – 38.3 PIK3CA 5 40.0..."

Clinical • Metastases • Colorectal Cancer • Oncology • BRAF • BRCA2 • CCND1 • CDK6 • EGFR • HER-2 • PIK3CA • RAS • TP53

A Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001) (clinicaltrials.gov) - P2 | N=66 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Jun 2026 ➔ Dec 2026

Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

HER2CLIMB-05: Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer. (ASCO 2023) - P3 | "Despite advances in 1L SOC, most patients progress during maintenance therapy with T + P. Tucatinib is a tyrosine kinase inhibitor (TKI) approved in combination with T and capecitabine for adults with HER2+ MBC, with and without brain metastases (BM). Enrollment is ongoing in the US, Canada, Brazil, APAC and EU countries with additional sites planned. Clinical trial information: NCT05132582."

Clinical • Combination therapy • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Summary of Research: HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination with Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer. (PubMed, Target Oncol) - P3 | "The safety profile of tucatinib plus maintenance therapy was consistent with the known toxicities of each individual drug. The HER2CLIMB-05 regimen, with its high efficacy and manageable toxicity, represents a valuable option for first-line maintenance therapy in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer."

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

A single-arm, phase II study of sequential therapy with curative intent in de novo HER2+ metastatic breast cancer: The SAPPHO study. (ASCO 2026) - P2 | "Treatment consists of an induction regimen (trastuzumab-pertuzumab-taxane [THP] x 4 cycles, followed by trastuzumab deruxtecan [TDXd] x 6 cycles, followed by trastuzumab emtansine [TDM1]-tucatinib x 4 cycles), followed by a maintenance regimen (HP-tucatinib for 1 yr). Patient-reported outcomes will be analyzed, including quality of life, illness intrusiveness, financial toxicity, anxiety, distress about cancer progression, perception of benefit and risk of progression. SAPPHO began enrollment in Q3 2024, and the study is open at 4 US sites within the Translational Breast Cancer Research Consortium (NCT05721248)."

Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Mood Disorders • Oncology • Solid Tumor • HER-2

Tucatinib and trastuzumab for previously treated HER2−mutated metastatic breast cancer (SGNTUC−019): A phase 2 basket study. (ASCO 2024) - P2 | "Tucatinib (TUC) is a tyrosine kinase inhibitor highly selective for HER2 and is approved for previously treated HER2+ MBC with or without brain metastases in combination with trastuzumab (Tras) and capecitabine...Pts with HR+ disease also received fulvestrant (F; 500 mg IM once every 4 wks starting from cycle 1 day 1, and cycle 1 day 15)... The investigational combination of TUC and Tras, plus F in pts with HR+ disease, was well tolerated and had clinical activity in pts with previously treated HER2-mut MBC. The results support further evaluation of the combination of TUC and Tras as a potential treatment option for this pt population."

Metastases • P2 data • Pan tumor • Breast Cancer • Cardiovascular • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Hypertension • Oncology • Solid Tumor • HER-2

Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases: Updated Exploratory Analysis of the HER2CLIMB Randomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "The 612 patients, including those with active or stable BMs, had ERBB2-positive MBC previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine. This subgroup analysis found that tucatinib in combination with trastuzumab and capecitabine improved OS while reducing the risk of developing new brain lesions, further supporting the importance of this treatment option for patients with ERBB2-positive MBC, including those with BMs. ClinicalTrials.gov Identifier: NCT02614794."

Clinical • Combination therapy • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Oncology • Solid Tumor • HER-2

Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results. (ASCO 2024) - P2 | "This is the first prospective evidence of clinically meaningful benefit including objective responses, symptom improvement, and quality of life, along with extended survival, with a systemic regimen for LM from HER2+ BC. These data support the trend toward using systemic therapy as an initial approach in CNS metastases."

P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A phase I/Ib study of IAM1363, a selective and brain penetrant HER2 inhibitor in participants (pts) with advanced cancers harboring HER2 alterations (ESMO 2025) - P1 | "Three of the 4 pts with PRs had received prior T-DXd. The pt with breast cancer had also received prior tucatinib...Most AEs were low grade and manageable in the outpatient setting. Antitumor activity was observed across disease types and HER2 alterations and was evident both systemically and intracranially in heavily pretreated pts."

Clinical • Metastases • P1 data • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • EGFR