HER3-DXd for Cancer
Recruiting in Palo Alto (17 mi)
+55 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Daiichi Sankyo, Inc.
Must not be taking: Chronic corticosteroids, Anti-HER3 ADCs
Disqualifiers: HER2-positive gastric cancer, Nasopharyngeal cancer, Mucosal melanoma, ILD, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced or metastatic solid tumors. The study is enrolling cohorts of participants with melanoma \[cutaneous/acral\], squamous cell carcinomas of the head and neck (SCCHN), and HER2-negative gastric cancerovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, and prostate cancer.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on chronic systemic corticosteroids over 10 mg of prednisone or similar medications. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug HER3-DXd for cancer?
Research shows that HER3-DXd, also known as Patritumab deruxtecan, has been effective in treating certain types of breast cancer and non-small-cell lung cancer by targeting a specific protein (HER3) involved in cancer growth. Studies have demonstrated its ability to reduce tumor size and improve outcomes in patients with these cancers.
12345Is HER3-DXd safe for humans?
HER3-DXd, also known as Patritumab deruxtecan, has been tested in several studies for different types of cancer, including breast and lung cancer. It has shown a tolerable safety profile, meaning that while there may be some side effects, they are generally manageable for patients.
12346What makes the drug HER3-DXd unique compared to other cancer treatments?
HER3-DXd is unique because it is an antibody-drug conjugate that specifically targets the HER3 protein, which is often found in high levels in certain cancers and linked to poor outcomes. It combines a monoclonal antibody with a chemotherapy agent, allowing it to deliver the drug directly to cancer cells, potentially increasing effectiveness and reducing side effects.
12346Eligibility Criteria
This trial is for adults with advanced or metastatic solid tumors, including specific types of melanoma, head and neck cancers, gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma and prostate cancer. Participants must have experienced disease progression after prior treatments.Inclusion Criteria
My cancer has worsened despite treatment with a PBC regimen and possibly anti-PD-1 therapy.
My cancer is in the stomach or where the stomach meets the esophagus.
My melanoma worsened despite BRAF/MEK inhibitor treatment.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive HER3-DXd monotherapy 5.6 mg/kg every 3 weeks
27 months
Every 3 weeks (in-person)
Pharmacokinetic Assessment
Pharmacokinetic parameters such as AUClast, AUCtau, Cmax, Tmax, and Ctrough are assessed
Cycles 1-4, 6, 8 (each cycle is 21 days)
Multiple visits per cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests HER3-DXd monotherapy in patients with various solid tumors. It focuses on those who've had previous treatments but their disease has progressed. The goal is to see how effective this new therapy is on its own.
1Treatment groups
Experimental Treatment
Group I: HER3-DXd MonotherapyExperimental Treatment1 Intervention
Participants with locally advanced or metastatic cancer (melanoma, head and neck, gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, and prostate cancer) will receive an intravenous infusion of HER3-DXd monotherapy 5.6 mg/kg every 3 weeks (Q3W).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale Cancer CenterNew Haven, CT
Memorial Sloan Kettering HospitalNew York, NY
City of HopeDuarte, CA
Washington University, School of MedicineSaint Louis, MO
More Trial Locations
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Who Is Running the Clinical Trial?
Daiichi Sankyo, Inc.Lead Sponsor
Daiichi SankyoLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. [2023]Human epidermal growth factor receptor 3 (HER3) is broadly expressed in breast cancer; high expression is associated with an adverse prognosis. Patritumab deruxtecan (HER3-DXd) is an investigational HER3-targeted antibody-drug conjugate that is being evaluated as a novel treatment in HER3-expressing advanced breast cancer in the U31402-A-J101 study.
Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study. [2023]Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %) + 1.3 × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer.
Population Pharmacokinetics of Patritumab Deruxtecan in Patients With Solid Tumors. [2023]Patritumab deruxtecan is an antibody-drug conjugate consisting of a fully human monoclonal antibody against human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. As part of the pharmacometric analysis informing dose selection for later-stage development, population pharmacokinetics (PK) analysis of patritumab deruxtecan was conducted with pooled serum PK data from patients with HER3-expressing solid tumors (from 3 phase 1/2 studies in breast, lung, and colorectal cancer; N = 425) treated over the dose range of 1.6 to 8.0 mg/kg intravenously every 3 weeks. Population PK modeling for deruxtecan (DXd)-conjugated antibody (representing patritumab deruxtecan) and unconjugated MAAA-1181a (DXd, payload) was carried out sequentially. DXd-conjugated antibody PK was described using a 2-compartment model with parallel linear and nonlinear clearance. Unconjugated DXd PK was described using a 1-compartment model with linear clearance and release of DXd as a first-order, time-dependent function of the level of DXd-conjugated antibody in the central compartment. Preliminary covariate evaluation was conducted for prespecified covariates of pharmacological plausibility and clinical interest. The final model retained weight (on linear clearance and central volume) and albumin level, sex, and tumor type (on linear clearance) for DXd-conjugated antibody, and weight (on release rate constant) and hepatic function (on clearance) for unconjugated DXd. Effects of these covariates on the exposure metrics were generally mild and did not require dose adjustment for subpopulations in subsequent development. Further PK characterization for patritumab deruxtecan will evolve with emerging data.
HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. [2023]Label="PURPOSE" NlmCategory="OBJECTIVE">Patritumab deruxtecan, or HER3-DXd, is an antibody-drug conjugate consisting of a fully human monoclonal antibody to human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. We assessed the efficacy and safety of HER3-DXd in patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC).
SOLTI-1805 TOT-HER3 Study Concept: A Window-of-Opportunity Trial of Patritumab Deruxtecan, a HER3 Directed Antibody Drug Conjugate, in Patients With Early Breast Cancer. [2021]Background: Preclinical data support a key role for the human epidermal growth factor receptor 3 (HER3) pathway in hormone receptor (HR)-positive breast cancer. Recently, new HER3 directed antibody drug conjugates have shown activity in breast cancer. Given the need to better understand the molecular biology, tumor microenvironment, and mechanisms of drug resistance in breast cancer, we designed this window-of-opportunity study with the HER3 directed antibody drug conjugate patritumab deruxtecan (HER3-DXd; U3-1402). Trial Design: Based on these data, a prospective, multicenter, single-arm, window-of-opportunity study was designed to evaluate the biological effect of patritumab deruxtecan in the treatment of naïve patients with HR-positive/HER2-negative early breast cancer whose primary tumors are ≥1 cm by ultrasound evaluation. Patients will be enrolled in four cohorts according to the mRNA-based ERBB3 expression by central assessment. The primary endpoint is a CelTIL score after one single dose. A translational research plan is also included to provide biological information and to evaluate secondary and exploratory objectives of the study. Trial Registration Number: EudraCT 2019-004964-23; NCT number: NCT04610528.
HERTHENA-Lung01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC. [2023]Limited treatment options exist for EGFR-mutated NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy. HER3 is highly expressed in EGFR-mutated NSCLC, and its expression is associated with poor prognosis in some patients. Patritumab deruxtecan (HER3-DXd) is an investigational, potential first-in-class, HER3-directed antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. In an ongoing phase I study, HER3-DXd demonstrated promising antitumor activity and a tolerable safety profile in patients with EGFR-mutated NSCLC, with or without identified EGFR TKI resistance mechanisms, providing proof of concept of HER3-DXd. HERTHENA-Lung01 is a global, registrational, phase II trial further evaluating HER3-DXd in previously treated advanced EGFR-mutated NSCLC. Clinical Trial Registration: NCT04619004 (ClinicalTrials.gov); 2020-000730-17 (EudraCT).