New Trials in Breast Cancer: Could Your Patient Benefit?

Helen Leask

November 21, 2022

Several clinical trials in breast cancer have started in recent months. Maybe one of your patients could benefit from taking part.

HER2/neu-positive breast cancer with high risk of recurrence following neoadjuvant and postoperative adjuvant standard of care. Adult patients with this type of breast cancer who have no residual disease can join a randomized phase 3 study testing an investigational immunotherapy called GLSI-100 (developed by Greenwich LifeSciences). The treatment is a combination of GP2 — a "peptide vaccine" derived from HER2 that is designed to alert T cells to the presence of cells expressing HER2 — and granulocyte-macrophage colony-stimulating factor. Participants who are HLA-A*02 positive and are assigned to the investigational treatment will receive six intradermal injections of GLSI-100 over 6 months, then a booster every 6 months for a maximum of 2.5 years. People in the placebo group will receive placebo injections. Patients who are not HLA-A*02 positive will receive the same GLSI-100 regimen as the investigational group, but there is no placebo comparator. The outcome measure is invasive breast cancer–free survival over approximately 4 years. Overall survival (OS) and quality of life (QoL) are secondary measures. Sites in Arizona, California, Maryland, Nebraska, New York, Oregon, Texas, and Virginia started recruiting with a goal of 598 participants in August 2022. More details at

"We have been waiting (and hoping) for a vaccine to reduce recurrence for decades," commented Medscape columnist Kathy Miller, MD, professor of oncology and medicine at the Indiana University School of Medicine, Indianapolis. "Fingers crossed," she added.

ER-positive, HER2-negative locally advanced/metastatic breast cancer. Adults with this type of breast cancer who have previously received cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) plus endocrine therapy can enter a randomized, phase 3, open-label study that is testing a new drug, giredestrant, in combination with standard treatments. Giredestrant (from Genentech) is an experimental oral selective estrogen-receptor degrader (SERD). Individuals in the study will take once-daily tablets of either giredestrant or exemestane (Aromasin) plus everolimus (Afinitor). Men and premenopausal or perimenopausal women will also receive an injected LHRH agonist every 4 weeks. Participants will also receive a dexamethasone mouth rinse to stave off stomatitis/mucositis. The study opened in August 2022 at 24 sites in 14 states and seeks to enroll 320 participants. The primary outcome measure is progression-free survival (PFS). OS and QoL are secondary outcomes. More details at

Miller remarked that there have been mixed results this year with this class of drugs. "Oral SERDS have had an up-and-down year. Clearly they are not all the same," she said.

ER-positive, HER2-negative locally advanced/metastatic breast cancer. Individuals with this type of breast cancer for whom therapy with CDK4/6 and aromatase inhibitors has failed can join an open-label, randomized, phase 3 study testing another new drug, gedatolisib, plus standard treatment. Gedatolisib (from Celcuity) is an experimental drug that blocks the activation of the P13K/mTOR pathway, a key signaling pathway in many cancers. In the trial, all patients will receive monthly fulvestrant (Faslodex) injections for a maximum of 4 years. In addition, two groups of patients (those with and those without PIK3CA mutations) will receive intravenous gedatolisib weekly for 3 weeks out of 4, plus oral palbociclib (Ibrance). Two more groups, one comprising patients with the mutation and one comprising patients without it, will receive only gedatolisib. A fifth group of patients, all with PIK3CA mutations, will receive oral alpelisib (Piqray) with fulvestrant. A sixth group of participants, whose tumors do not have PIK3CA mutations, will receive fulvestrant alone. Sites in Arkansas, Florida, Georgia, Maryland, Nebraska, and New York opened their doors in September 2022. Trial centers in 19 more US states and 22 other countries are planned, with a goal of 701 participants in total. PFS is the primary outcome; OS and QoL are secondary outcomes. More details at

Miller commented, "Balancing potential benefit and toxicity has been a challenge with this class of drugs, but the potential to extend benefit of hormone therapy for longer is important to patients."

HR-positive, HER2-negative locoregional recurrent, resected breast cancer. People in this clinical situation who have no distant metastases are eligible for a single-arm, open-label, phase 2 study to see whether disease recurrence can be slowed by ribociclib (Kisqali). The drug is already approved for use in advanced/metastatic breast cancer. All participants will take daily oral ribociclib for 3 weeks out of every 4 plus physician's choice of endocrine therapy. Unless they have undergone bilateral oophorectory, premenopausal women will also receive ovarian suppression. The University of Illinois Cancer Center, Chicago, started recruiting in September 2022 with a goal of 200 participants. Recurrence-free survival over 3 years is the primary endpoint, OS is a secondary endpoint, and QoL will not be tracked. More details at

Miller observed that this trial is testing adjuvant therapy "in a very high-risk group."

Metastatic breast cancer refractory to first-line treatment for advanced disease. Patients aged 18 to 70 years in this scenario can join an open-label phase 2 National Cancer Institute trial of T-cell receptor gene therapy. The participants' own lymphocytes will be engineered to express T-cell receptors appropriate to each patient's unique tumor neoantigens that will, ideally, recognize and destroy tumor cells expressing those antigens. Peripheral blood lymphocytes will be collected from participants by apheresis. When the tailored treatment is ready, each person will stay in the hospital 1 week before and approximately 3–4 weeks after treatment and will return for follow-up visits at 6 and 12 weeks. Individuals who respond will attend the clinic every 3–6 months for a further 3 years. Subsequently, a follow-on study will track all responders for approximately 12 years. The National Institutes of Health Clinical Center in Bethesda, Maryland, will begin recruiting the planned 210 trial participants with a range of solid cancers in November. The primary outcome is clinical response, as assessed by objective tumor regression. OS and QoL will not be assessed in the first 3-year trial. More details at

ER-positive, HER2-negative early breast cancer. Adult patients with this type of breast cancer who have taken endocrine therapy for 2 to 5 years can participate in a randomized, open-label, phase 3 study testing the effectiveness of investigational SERD imlunestrant (an Eli Lilly hopeful) against standard hormone therapy. For up to 10 years, one group of participants will take oral imlunestrant daily. A second group will receive physician's choice of either tamoxifen (Nolvadex), anastrozole (Arimidex), letrozole (Femara), or exemestane (Aromasin). Research sites across 32 countries and 32 US states started recruiting 6000 participants in October 2022. The primary outcome is invasive disease–free survival. Overall survival and QoL are secondary measures. More details at

All trial information is from the US National Library of Medicine of the National Institutes of Health (online at

Miller has a regular Medscape column, Miller on Oncology. She has disclosed no relevant financial relationships.

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