Grade ≥3 TEAEs included thrombocytopenia, hypokalemia, increased ALT levels, increased AST levels, fatigue, and hypophosphataemia. Three dose-limiting toxicities were observed in 7 patients at the 350-mg dose, consisting of drug hypersensitivity, fatigue, and vomiting. Among the 50 patients treated at the MTD, the median PFS was 8.2 months (95% CI, 4.8-10.3); patients who had previously received both trastuzumab and pertuzumab (Perjeta), however, had a median PFS of 6.5 months (95% CI, 4.1-9.2). Breast Cancer News is strictly a news and information website about the disease. Serious adverse events were observed in 37%, with 6 of these events potentially related to tucatinib treatment: cardiac failure and fatigue, pyrexia and drug hypersensitivity, vomitinib and hypokalemia, and pneumonia. Patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. FDA Approves Phesgo as Injection Treatment for HER2-positive Breast Cancers, FDA Approves Tukysa for Advanced HER2-positive Breast Cancer. All rights reserved. Patients are eligible regardless of brain metastasis or prior Perjeta treatment. It has received orphan drug status by the U.S. Food and Drug Administration for the treatment of breast cancer patients with brain metastases. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. A phase III trial, HER2CLIMB-02, has been initiated to investigate the combination of tucatinib and ado-trastuzumab emtansine in patients with locally advanced or metastatic HER2-positive breast cancer.� … Among 48 evaluable patients, the CBR was 58%. That trial recently met its primary endpoint of progression-free survival as well as two key secondary measures: the tucatinib combo reduced the risk of disease progression or death by 46% compared to standard Xeloda plus trastuzumab, and cut the risk of death by 34%. ... ONT-380 is advancing in one Phase 2 and three Phase … The study is ongoing and recruiting participants at three U.S. sites: the Center for Cancer and Blood Disorders/RCCA in Bethesda, Maryland, the Nebraska Cancer Specialists in Omaha, Nebraska, and the Summit Medical Group in Florham Park, New Jersey. Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Subjects With Unresectable Locally-advanced or Metastatic HER2+ Breast Cancer Seattle Genetics Announces Initiation of Phase 3 Clinical Trial of Tucatinib in Combination with Ado-trastuzumab Emtansine (T-DM1, Kadcyla®) for Patients with Advanced or Metastatic HER2-Positive Breast Cancer [press release]. The enrolling phase III trial is based off of the results of a phase Ib trial, in which the agent demonstrated an acceptable safety profile in combination with T-DM1 in patients with HER2-positive metastatic breast cancer.2. TUCATINIB (ONT-380 or ARRY-380) is an orally active, reversible and selective small-molecule HER2 inhibitor invented by Array and licensed to Cascadian Therapeutics (previously named Oncothyreon) for development, manufacturing and commercialization. All rights reserved. In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 … Patients with untreated brain metastases not needed immediate therapy or previously treated and stable brain metastases were able to enroll in the trial. Tagged Ado-trastuzumab emtansine, HER2-positive breast cancer, HER2CLIMB Phase 2 trial, HER2CLIMB-02, Kadcyla, Seattle Genetics, tucatinib. This trial has the potential to support tucatinib use in earlier lines of therapy.”. Seattle Genetics, Inc. today announced dosing of the first patient in HER2CLIMB-02, a randomized phase 3 clinical trial evaluating investigational agent tucatinib versus placebo, in … Patients had a median age of 51 (range, 44-63) and most had an ECOG performance status of 1. The primary endpoint was to establish the maximum tolerated dose and recommended phase 2 dose of tucatinib, This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast … Patients received 300 or 350 mg of oral tucatinib twice per day plus 3.6 mg/kg of intravenous T-DM1 once in every 21-day cycle. © 2021 MJH Life Sciences and Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways. Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. Frequent adverse events considered to be related to tucatinib included nausea, diarrhea, fatigue, increased AST levels, vomiting, decreased appetite, increased ALT levels, and hypokalemia. A Phase 3 trial exploring a combination of Seattle Genetics‘ tucatinib plus standard Kadcyla (ado-trastuzumab emtansine) in people with advanced HER2-positive breast cancer has dosed its first participant, the company announced. Tucatinib, sold under the brand name Tukysa, is a small molecule inhibitor of HER2 for the treatment of HER2-positive breast cancer. In addition to HER2CLIMB-02, Seattle Genetics is sponsoring a Phase 2 clinical trial called HER2CLIMB (NCT02614794), which is studying a combination of tucatinib plus standard Xeloda (capecitabine) and trastuzumab in advanced HER2-positive breast cancer patients who received prior treatment with trastuzumab, Perjeta, and Kadcyla. Bothell, WA: Seattle Genetics Inc; October 10, 2019. https://bwnews.pr/33i2fnm. As such, the 300 mg twice daily dose was set as the maximum tolerated dose (MTD). A phase III trial, HER2CLIMB-02, has been initiated to investigate the combination of tucatinib and ado-trastuzumab emtansine in patients with locally advanced or metastatic HER2-positive breast cancer. The results of the trial will support registration for tucatinib in the United States. The HER2CLIMB-02 double-blind, phase 3 trial was designed to evaluate the efficacy and safety of tucatinib plus trastuzumab emtansine in patients with unresectable locally advanced or metastatic … In terms of AEs leading to tucatinib or placebo discontinuation, investigators reported 6% in the tucatinib arm and 3… Accessed October 10, 2019. received orphan drug status by the U.S. Food and Drug Administration for the treatment of breast cancer patients with brain metastases, Center for Cancer and Blood Disorders/RCCA, Enhertu Approved in UK for Inoperable, Advanced Breast Cancer, Phase 2 Trial Will Test IRX-2 Combined With Keytruda, Chemotherapy for TNBC, Tukysa Combo Approved in EU for Advanced HER2-Positive Breast Cancer, FDA’s New ‘Project Patient Voice’ to Share Symptoms Data From Cancer Trials. Be the first to rate this post. Patients in the trial are randomized 1:1 to either 300 mg tucatinib twice daily or placebo plus 3.6 mg/kg intravenous T-DM1 in 21-day cycles. In the 350 mg cohort, the median number of prior HER2-targeted therapies was 1 (range, 1-2) and only 2 patients (29%) had brain metastases and had undergone whole-brain radiation. We are sorry that this post was not useful for you! It does not provide medical advice, diagnosis or treatment. There are two phases to this trial: the Double-blind Phase and the Unblinded Phase. No votes so far! This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Tucatinib is an oral investigational small molecule inhibitor of the HER2 receptor with the ability to cross the blood-brain barrier, and holds promise in fighting brain metastasis in people with HER2-positive cancers. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. Many HER2-targeted treatments exist for breast cancer patients, including trastuzumab and Perjeta (pertuzumab) — antibodies that target and inhibit HER2 — and Kadcyla (ado-trastuzumab emtansine), which is trastuzumab bound to a toxic payload. However, patients may still see their disease progress after all these treatments. “This trial has the potential to support tucatinib use in earlier lines of therapy.”. HER2CLIMB-02: A randomized, double-blind, phase 3 study of tucatinib or placebo with T-DM1 for unresectable locally-advanced or metastatic HER2+ breast cancer #OT-28-01 Ongoing Trials … The median DOR was 6.9 months (95% CI, 2.8-19.8). There was a modest increase in liver function, particularly grade 3, at around 5% for tucatinib versus 0.5%; the PPE syndrome was a bit higher and really [with] no major difference in grade 3 at 13% versus 9%. The trial — called HER2CLIMB-02 (NCT03975647) — is enrolling up to 460 adult patients with metastatic or inoperable, locally advanced disease who received prior treatment with a taxane chemotherapy and trastuzumab. The study will randomly assign participants to receive either oral tucatinib or a placebo, twice a day, plus intravenous injections of Kadcyla once every three weeks. A phase III trial, HER2CLIMB-02, has been initiated to investigate the combination of tucatinib and ado-trastuzumab emtansine (T-DM1, Kadcyla) in patients with locally advanced or metastatic HER2-positive breast cancer (NCT03975647).1The results of the trial will support registration for tucatinib in the United States. Methods: MOUNTAINEER-02 (NCT04499924) is a phase 2/3 study evaluating TUC and Tras with the 2nd-line standard of care, Ram and Pac. HER2CLIMB-02 is a global, randomized, double-blind, placebo-controlled, phase III study enrolling pts with centrally confirmed HER2+, unresectable, locally advanced, or MBC previously treated with Tras and taxane (in any setting), and ECOG ≤1. Dose interruptions for tucatinib were needed in 32 patients and 5 patients discontinued tucatinib due to an adverse event. The trial’s results are expected to be included in Seattle Genetics’ application seeking approval for tucatinib in the U.S. for this indication. In people with brain metastasis, the risk of disease progression or death was lowered by more than half (52%). Main outcomes and measures: Safety assessments, pharmacokinetics, and response were assessed using RECIST 1.1 every 2 cycles for 6 cycles, followed by every 3 … The results of several ongoing phase 3 … A modified 3 + 3 dose-escalation design was used to determine the recommended phase 2 dose, starting with tucatinib in combination with capecitabine or trastuzumab, and subsequently evaluating the triplet combination. Interventions: Tucatinib 300 mg or 350 mg administered orally twice per day for 21 days and T-DM1 3.6 mg/kg administered intravenously once every 21 days. Visit Breast Cancer News's profile on Pinterest. Fifty patients were treated with 300 mg tucatinib twice daily, and in this cohort, patients had received a median of 2 prior HER2-directed agents (range, 1-3). “We are building a comprehensive strategy for tucatinib in combination with other medicines across a range of HER2-positive cancers,” Roger Dansey, MD, chief medical officer at Seattle Genetics, the company developing tucatinib, said in a press release. A Phase 3 trial exploring a combination of Seattle Genetics' tucatinib plus standard Kadcyla (ado-trastuzumab emtansine) in people with advanced HER2-positive breast cancer has … HER2CLIMB-02 was designed to determine if adding tucatinib to Kadcyla could delay cancer progression and death in people who had failed prior taxane chemotherapy and trastuzumab. Safety will also be assessed. Pts receive TUC 300 mg or placebo PO BID, Tras (6 then 4 mg/kg) … HER2CLIMB-02 is a multi-center, randomized, double-blind, placebo-controlled phase 3 trial designed to evaluate tucatinib versus placebo, in combination with T-DM1, in patients with unresectable locally … When breast cancers are driven by the protein HER2, which acts to send signals that drive excessive cell growth and is associated with more aggressive cancers, the standard approach is targeted therapy against this protein. Tucatinib plus trastuzumab and capecitabine extended OS among patients with brain metastases from HER2-positive breast cancer, according to findings from a randomized phase 3 study … In addition to progression-free survival — the trial’s main goal — the researchers will also measure overall survival, the time without disease worsening, or death in people with brain metastasis at the study’s start, and the proportion of patients who respond to treatment, as well as duration of responses. BOTHELL, WA, USA I October 10, 2019 I Seattle Genetics, Inc. (Nasdaq:SGEN) today announced dosing of the first patient in HER2CLIMB-02, a randomized phase 3 clinical trial evaluating investigational agent tucatinib … In the Unblinded Phase, patients on placebo may be offered tucatinib. Eligible patients will have previously received trastuzumab and a taxane, and prior pertuzumab is permitted. The randomized, double-blind phase III HER2CLIMB-02 trial is exploring the potential of the tucatinib/T-DM1 combination versus T-DM1 alone in patients with unresectable locally advanced or metastatic HER2-positive breast cancer. The ORR in 34 evaluable patients with measurable disease was 47%, including 1 complete response and 15 partial responses. It was developed by Array BioPharma and licensed to Cascadian … Borges VF, Ferrario C, Aucoin N, et al. “We are pleased to advance this tucatinib clinical trial with the vision of improving combination outcomes for patients with HER2-positive metastatic breast cancer who receive T-DM1. The design allowed at least six evaluable patients to be enrolled per tucatinib … Tucatinib is an oral tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. The investigators recommended 300 mg twice per day as the phase II dose for tucatinib. In the Double-blind phase, participants were randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab. The most common treatment-emergent adverse events (TEAEs) among patients treated at the MTD were nausea (72%), diarrhea (60%), fatigue (56%), epistaxis (44%), headache (44%), constipation (42%), vomiting (42%), and decreased appetite (40%). Sixty percent of these patients had brain metastases and 62% had not received radiotherapy for their brain metastases. In the patients with brain metastases treated at the MTD (n = 30), the median PFS was 6.7 months (95% CI, 4.1-10.2) and the DOR was 6.9 months (95% CI, 1.45-19.48). BOTHELL, Wash.--(BUSINESS WIRE)-- Seattle Genetics, Inc. (Nasdaq:SGEN) today announced dosing of the first patient in HER2CLIMB-02, a randomized phase 3 clinical trial evaluating investigational agent tucatinib … Breast Swelling & Inflammatory Breast Cancer, Albumin-Bound Paclitaxel (Nab-Paclitaxel or Abraxane), Cyclophosphamide (Clafen, Cytoxan, and Neosar), Chemo and Cocktails: A Young Survivor’s Guide. Of 14 of these patients with measurable brain metastases, the brain-specific ORR was 36%. both. Already the first patient has been dosed in the trial and 460 total patients are expected to be enrolled. “We are building a comprehensive strategy for tucatinib in combination with other medicines across a range of HER2-positive cancers,” Roger Dansey, MD, chief medical officer at Seattle Genetics, said in a news release. The most common treatment-emergent adverse events at that recommended phase II dose included diarrhea … © 2021 MJH Life Sciences™ , Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways. A Randomized, Double-blind, Placebo-controlled, Active Comparator Phase 2/3 Study of Tucatinib in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Subjects With Previously … The primary endpoint is progression-free survival (PFS) by RECIST v1.1 criteria and secondary endpoints include overall survival, objective response rate (ORR), duration of response (DOR), clinical benefit rate (CBR), and safety. Tucatinib, on the other hand, is a member of a class of drugs known as tyrosine kinase inhibitors (TKIs). In the dose-escalation phase, a modified 3 + 3 dose-escalation design was used to determine the recommended phase 2 dose of tucatinib. Tucatinib is an oral HER2-specific small molecule tyrosine kinase inhibitor. Randomized double blind phase 3 study of tucatinib or placebo in combination with ado trastuzumab e | Providence Oregon Study Number: RWF_SGNTUC-016 Randomized, double-blind, phase 3 study of tucatinib or placebo … In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 … The open-label, multicenter, dose-escalation study enrolled 57 women with HER2-positive metastatic breast cancer with or without stable brain metastases who had previously been treated with trastuzumab (Herceptin) and a taxane. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. These drugs work by binding to the part of the HER2 protein that is inside the cell and preventing it from sending signals that promote cell growth. Copyright © 2013-2021 All rights reserved. Click here to subscribe to the Breast Cancer News Newsletter! HER2CLIMB-02 is a multi-center, randomized, double-blind, placebo-controlled phase 3 trial designed to evaluate tucatinib versus placebo, in combination with T-DM1, in patients with … “We are pleased to advance this tucatinib clinical trial with the vision of improving combination outcomes for patients with HER2-positive metastatic breast cancer who receive T-DM1,” he said.