zanidatamab (ZW25)

P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Trial primary completion date: Aug 2024 --> Jul 2025

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=52, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Apr 2025 --> Sep 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

P2, N=87, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> Jul 2024

Currently, both pembrolizumab and nivolumab have been approved for the first-line treatment of tumors with positive PD-L1 expression...The antibody-drug conjugate trastuzumab-deruxtecan is a promising second-line treatment option for HER2-positive tumors after treatment failure with trastuzumab.In addition, the bispecific antibody zanidatamab shows promising results in first-line treatment. New targeted therapies against CLDN18.2 and FGFR2b are showing promising results. The anti-claudin 18.2 (CLDN18.2) antibody zolbetuximab leads to improved survival compared to chemotherapy alone in patients with CLDN18.2 positive disease in first-line therapy, with approval expected in 2024.

P1, N=279, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jun 2024 --> Oct 2024

P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Oct 2026 --> Jul 2025 | Trial primary completion date: Nov 2025 --> Aug 2024

Researchers have developed monoclonal antibodies like Trastuzumab and Pertuzumab against HER2 receptors, which have proven highly beneficial in cancer therapy. Bispecific antibodies like Zanidatamab and antibody-drug conjugates like T-DM1 have been developed to overcome the resistance associated with monotherapy. Small molecules such as Lapatinib, Neratinib, and Pyrotinib were initially developed for treating breast cancer...This comprehensive review covers the structural characteristics of HER2, the HER family signaling pathway mechanism, recent findings regarding HER2 receptor involvement in various cancers, and diverse HER2-targeted therapies. This information provides a comprehensive understanding of HER2-targeted strategies in the evolving field of cancer treatment.

The results of this study support the potential for zanidatamab as a new therapy for people with HER2-positive biliary tract cancer after they had already received chemotherapy. More research is occurring to support these results.Clinical Trial Registration: NCT04466891 (HERIZON-BTC-01 study).

P3, N=550, Recruiting, Jazz Pharmaceuticals | Not yet recruiting --> Recruiting | Trial completion date: Apr 2031 --> Nov 2031 | Trial primary completion date: Apr 2031 --> Sep 2028

P3, N=918, Recruiting, Jazz Pharmaceuticals | Trial completion date: Feb 2026 --> Jul 2025

P3, N=800, Recruiting, UNICANCER | Not yet recruiting --> Recruiting

P3, N=550, Not yet recruiting, Jazz Pharmaceuticals

P3, N=918, Recruiting, Jazz Pharmaceuticals | Trial completion date: Jul 2025 --> Feb 2026 | Trial primary completion date: Jun 2024 --> Dec 2024

P3, N=300, Enrolling by invitation, BeiGene | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Aug 2024 --> Dec 2026

P1/2, N=52, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting | N=93 --> 52 | Trial primary completion date: Jul 2024 --> Oct 2024

P2, N=168, Recruiting, Canadian Cancer Trials Group | Not yet recruiting --> Recruiting

P2; Active, not recruiting --> Completed | Trial completion date: Feb 2025 --> Mar 2024 | Trial primary completion date: Feb 2025 --> Mar 2024

P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting | N=362 --> 74

P2; Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P3, N=286, Recruiting, Jazz Pharmaceuticals

We observed a low response rate to zanidatamab in recurrent HER2+ endometrial carcinoma/carcinosarcoma, which may be driven by downregulation of HER2 expression. Repeat HER2 testing should be considered prior to second-line HER2-directed therapy.

P1/2, N=71, Active, not recruiting, BeiGene | Phase classification: P1b/2 --> P1/2

P3, N=800, Not yet recruiting, UNICANCER

P2, N=168, Not yet recruiting, Canadian Cancer Trials Group | Initiation date: Oct 2023 --> Jan 2024

HERIZON-BTC-01 (NCT04466891), an ongoing, open-label, Phase 2b study, is assessing zani (20 mg/kg IV Q2W) in patients with HER2+ (gene amplification and immunohistochemistry 2+ or 3+ [Cohort 1] and 0 or 1+ [Cohort 2]), locally advanced, unresectable or metastatic BTC (gallbladder cancer, intra-/extra-hepatic cholangiocarcinoma) who received prior gemcitabine-containing treatment (tx). Patients with HER2+ BTC who responded to zani reported less pain and pain interference compared with BL, further supporting the development of zani as a tx option for these patients, with the goal of improving patient outcomes. Clinical trial information: NCT04466891. >Change from BL for each patient is post-BL value minus BL value; negative values for change from BL indicate better outcomes and positive indicate worse.

P2, N=51, Active, not recruiting, Jazz Pharmaceuticals | Phase classification: P2a --> P2

P2, N=87, Active, not recruiting, Jazz Pharmaceuticals | Phase classification: P2b --> P2

P1/2, N=93, Recruiting, Jazz Pharmaceuticals | Phase classification: P1b/2 --> P1/2 | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Apr 2024 --> Jul 2024

Trastuzumab deruxtecan, an antibody drug conjugate of trastuzumab with a topoisomerase inhibitor, was recently approved for the treatment of refractory HER2-positive advanced GAC patients...Here we review the current status of HER2-targeted therapy in GACs. We additionally review newer therapies under investigation and their potential role in HER2 GACs.

More recently, two monoclonal antibodies have demonstrated their efficacy in combination with oxaliplatin-based first-line chemotherapy, nivolumab (anti-PD1) for PD-L1 CPS ≥5 tumors, and zolbetuximab for tumors overexpressing Claudin 18.2. Recent years have seen the emergence of new drugs that have improved patient survival, such as trastuzumab in first-line for HER2-positive tumors, ramucirumab alone or in combination with paclitaxel in second-line, and trifluridine-tipiracil beyond the second-line treatment. Advanced gastric adenocarcinoma is a common disease with a poor prognosis whose treatment has for decades been based on cytotoxic chemotherapy, including platinum salts in first-line, and taxane or irinotecan in second or later line. In addition, regorafenib has been also showed effective in phase 3 trial for heavily pretreated patients. Based on phase 2 studies, trastuzumab-deruxtecan was approved in 2022 by the EMA for HER2-positive pretreated patients. This agent is currently evaluated in phase 3 study (DESTINY-Gastric04 trial), as are several other anti-HER2 (zanidatamab, margetuximab, tucatinib), immune checkpoint inhibitors, or targeted therapies (anti-FGFR2b).

Eligible pts had HER2+ (by local HER2 testing) and HR+, unresectable, locally advanced or mBC; ECOG PS ≤1; prior treatment with at least trastuzumab, pertuzumab, and T-DM1; and no prior CDK4/6 inhibitor...In the metastatic setting, pts received a median (range) of 4 (1-12) prior systemic regimens, 3 (1-10) prior different HER2-targeted therapies, and 1 (0-5) prior endocrine therapy; 12 (24%) pts had prior T-DXd and 11 (22%) had prior fulv... Zani + palbo + fulv showed a promising PFS6 and mPFS with durable responses. The safety profile was manageable. These results support further development of a novel chemotherapy-free treatment regimen for heavily pretreated pts with HER2+/HR+ mBC.

Background: The addition of trastuzumab+/-pertuzumab to chemotherapy has changed the natural history of earlyHER2+ breast cancer...Six received tamoxifen and 8 letrozole... Neoadjuvant zanidatamab demonstrates significant preliminary efficacy, (pCR/RCB-1 64%) with a good safety profile in patients with stage I node negative HER2+ BC. An update of efficacy and safety of all patients will be presented at the time of meeting

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Pts had received ≥1 prior systemic Tx for advanced disease, including gemcitabine. Lancet Oncol. 2023).

P2, N=168, Not yet recruiting, Canadian Cancer Trials Group

No abstract available

P2b, N=87, Active, not recruiting, Jazz Pharmaceuticals | Trial primary completion date: Oct 2022 --> Jul 2023

P2b, N=87, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Jun 2024 --> Oct 2024

P1, N=279, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Aug 2023 --> Jul 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

P2, N=362, Recruiting, Jazz Pharmaceuticals | Trial completion date: Apr 2024 --> Oct 2026 | Trial primary completion date: Mar 2023 --> Nov 2025

P2a, N=51, Active, not recruiting, Jazz Pharmaceuticals | N=86 --> 51 | Trial completion date: Jun 2023 --> Oct 2025 | Trial primary completion date: Dec 2022 --> Apr 2023