May 8, 2019 - Episode 1

FDA Approval in HER2+ Early Breast Cancer, Fast Track Designation in TNBC, and More


An FDA approval in HER2-positive early breast cancer, a fast track designation in triple-negative breast cancer, and promising findings in HER2-positive breast cancer, ovarian cancer, and chronic lymphocytic leukemia.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved ado-trastuzumab emtansine, also known as T-DM1, for use as an adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease following neoadjuvant trastuzumab and chemotherapy.

The approval is based on data from the phase III KATHERINE study, in which T-DM1 reduced the risk of invasive disease recurrence or death by 50% versus trastuzumab in this setting. The 3-year invasive disease-free survival rate was 88.3% with T-DM1 versus 77.0% with trastuzumab, leading to an absolute improvement of 11.3%.

The iDFS benefit with T-DM1 was upheld across key patient subgroups: operable disease at presentation, inoperable disease at presentation, negative hormone receptor status, positive HR status, trastuzumab as only anti-HER2 agent in the neoadjuvant setting, trastuzumab plus at least 1 anti-HER2 agent in the neoadjuvant setting, node-positive disease after neoadjuvant treatment, and node-negative disease after neoadjuvant treatment.

The agency reviewed and approved the application under the Real-Time Oncology Review and Assessment Aid pilot programs. The approval occurred 12 weeks following completion of the submission of the application.


Also in breast cancer, the FDA has granted a fast track designation to the CCR5 antagonist leronlimab for use in combination with carboplatin for the treatment of patients with CCR5-positive metastatic triple-negative disease.

The agent, which is given via injection, is being evaluated in clinical trials at sites that are initiating patient enrollment. The injection of the first patient with metastatic TNBC is expected to be imminent.

Leronlimab is an investigational humanized IgG4 monoclonal antibody that blocks CCR5, which appears to play multiple roles with implications in HIV infection, tumor metastases, and immune signaling. The agent has also been granted a fast track designation for use in combination with highly active antiretroviral therapy for patients with HIV infections.

Prior data showed that CCR5 potentially plays a central role in tumor invasion and metastasis and that increased CCR5 expression is an indicator of disease status in several cancers. Additionally, CCR5-blocking drugs can block tumor metastases in lab and preclinical models of aggressive breast and prostate cancers.


The antibody-drug conjugate [fam-] trastuzumab deruxtecan demonstrated encouraging responses in patients with unresectable and/or metastatic HER2-positive breast cancer that received prior treatment with ado-trastuzumab emtansine, according to topline findings from the phase II DESTINY-BreastO1 study.

The responses confirm the phase I data reported in an international, heavily pretreated HER2-positive breast cancer population. The safety and tolerability findings were also consistent with prior results of this agent.

These phase II results will be the basis for a biologics license application that will be submitted to the FDA in the second half of 2019.

The FDA previously granted [fam-] trastuzumab deruxtecan a breakthrough therapy designation in August 2017 for the treatment of patients with HER2-positive, locally advanced, or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression on T-DM1.

The designation was based on preliminary data from an ongoing phase I study, which showed promising activity and tolerable safety with the ADC in patients with HER2-positive and -expressing cancers.

Updated results of part 2 of the phase I study included 115 patients who received at least 1 dose of [fam-] trastuzumab deruxtecan, of which 111 were evaluable for confirmed response. Patients enrolled on this part of the study had a median 7 lines of prior therapy.

Data showed that the overall response rate was 59.5% and the disease control rate was 93.7% with [fam-] trastuzumab deruxtecan. Additionally, the median duration of response was 20.7 months, the median progression-free survival was 22.1 months, and the median overall survival has not yet been reached in the trial.


In ovarian cancer, the antibody-drug conjugate mirvetuximab soravtansine demonstrated a favorable benefit-risk profile in a prespecified subset of patients with folate receptor alpha—positive disease, following a comprehensive analysis of the phase III FORWARD I trial.

The news follows the company’s March 2019 announcement that mirvetuximab soravtansine missed the study’s primary endpoint of progression-free survival versus chemotherapy in patients with folate receptor alpha—positive, platinum-resistant ovarian cancer and in the overall patient population. Although PFS was longer with mirvetuximab soravtansine in the prespecified high folate receptor alpha–positive subgroup, it was not enough to reach statistical significance as per a prespecified statistical analysis plan. There was also no significant difference in PFS in the overall study population.

ImmunoGen, the developer of the antibody-drug conjugate, stated in the press release that it also plans to meet with the European Medicines Agency regarding conditional marketing authorization for mirvetuximab soravtansine in this setting.

Results of an expansion cohort of the phase I/II FORWARD II trial, which is exploring the combination of mirvetuximab soravtansine plus bevacizumab in patients with platinum-resistant, advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer, will be presented at the 2019 ASCO Annual Meeting.


Acalabrutinib demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus the combination of rituximab and either idelalisib or bendamustine in patients with previously treated chronic lymphocytic leukemia, meeting the primary endpoint of the phase III ASCEND trial.

Additionally, the safety and tolerability data were consistent with the known adverse event profile of the BTK inhibitor. Due to these interim data, the trial will end early, and full findings will be presented at an upcoming medical meeting.

Recent phase II data highlighted the benefit with acalabrutinib in both patients with newly diagnosed and relapsed/refractory CLL. In the open-label study, patients achieved ORRs as high as 100% with either of 2 doses of acalabrutinib.

Moreover, the phase III ELEVATE-TN trial is comparing the efficacy of obinutuzumab and chlorambucil, acalabrutinib plus chlorambucil, or acalabrutinib alone in treatment-naïve patients with CLL.


This week, we sat down with Dr Tiffany Traina, of Memorial Sloan Kettering Cancer Center, to discuss potential evolutions in the triple-negative breast cancer paradigm.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.