New Trials in Breast Cancer: Could Your Patient Benefit?

Several new clinical trials in breast cancer have opened in recent months. Perhaps one of your patients could benefit from taking part?

Human epidermal growth factor receptor 2–positive (HER2+) or HER2-low unresectable or metastatic breast cancer. Adults with this type of breast cancer who have received one to three chemotherapies may be eligible for a randomized, open-label, phase 2 trial of experimental antibody-drug conjugate (ADC) BB-1701. In part 1 of the study, participants will help determine the optimal dose of the drug, which carries an eribulin (Halaven) payload. They will receive one of the increasing doses of BB-1701 by intravenous (IV) infusion every 3 weeks. Individuals involved in part 2 of the study will be given the chosen dose by IV infusion every 3 weeks for up to approximately 3 years. Recruitment for the trial’s 135 participants started in April 2024 across nine US states and Japan. The primary outcomes are objective response rate and a suite of safety/tolerability measures. Overall survival (OS) is a secondary outcome, and quality of life (QoL) will not be tracked. More details at clinicaltrials.gov

When invited to comment on this trial, Elizabeth A. Sakach, MD, a medical oncologist at the Winship Cancer Institute of Emory University, Atlanta, who is not involved in the study, said that BB-1701 is an exciting new ADC with “promising” phase 1 results.

She added that unlike other ADCs for metastatic HER2+ breast cancer, “BB-1701 has not been observed to cause interstitial lung disease and could be a good treatment option in those who were at risk of [interstitial lung disease] or unfortunately experienced [interstitial lung disease] from prior therapies.”

Unresectable, locally advanced or metastatic estrogen receptor–positive (ER+)/HER2-negative breast cancer. Women and men with this diagnosis are being recruited for a randomized, open-label, phase 3 study to see if sacituzumab tirumotecan, another experimental ADC, is better at slowing tumor growth than standard “physician’s choice” therapy, with or without chemotherapy. Sacituzumab tirumotecan is an ADC with the same antibody as sacituzumab govitecan. Sacituzumab tirumotecan showed a “consistent clinical benefit independent of TROP2 expression” in a recent phase 3 study in metastatic triple-negative breast cancer (TNBC), said Sakach. In the new study, all participants will be given experimental therapy until progressive disease or discontinuation. Two groups of people will receive IV sacituzumab tirumotecan every 2 weeks. One group will also get pembrolizumab by IV every 6 weeks for up to approximately 2 years. The remaining individuals in the study will receive chemotherapy of their physicians’ choice. The study opened its doors to 1200 participants in April 2024 at sites in Maryland, New York, Puerto Rico, and 10 countries worldwide. The primary outcome is progression-free survival. QoL and OS are secondary outcomes. More details at clinicaltrials.gov

“It is important to study ADCs in combination with immunotherapy, given the growing evidence that ADCs can enhance the efficacy of immunotherapy drugs,” Sakach commented.

TNBC without a pathologic complete response after surgery. Adult patients in this clinical situation are sought for another randomized, open-label, phase 3 trial testing sacituzumab tirumotecan and pembrolizumab against standard therapy. In this study, one group of patients will receive IV pembrolizumab every 6 weeks, with or without standard oral capecitabine 2 weeks on, 1 week off, for 24 weeks. The other participants will be given IV pembrolizumab every 6 weeks plus IV sacituzumab tirumotecan every 2 weeks. Study centers across California, Illinois, Texas, Virginia, Australia, Israel, and South Korea started recruiting 1530 participants in June 2024. The primary endpoint is invasive disease–free survival. OS over approximately 8 years and QoL are secondary endpoints. More details at clinicaltrials.gov

Sakach said that the results of this study will be “practice changing” and are crucial to improve survival and outcomes for patients in early-stage, high-risk TNBC. “This is a high area of unmet need, given capecitabine is the only FDA-approved therapy in this space,” said Sakach.

Nonmetastatic breast cancer with radiation scheduled. People at this point in their breast cancer treatment who are co-residing with an intimate partner may be interested in a randomized, phase 2 study testing whether exercising together prevents decline in the couple’s physical and mental health as one partner undergoes radiation. One group of couples will participate in a program called Exercise Together by videoconference. A second group will simply receive exercise-related educational materials. The Oregon Health & Science University’s Knight Cancer Institute in Portland, Oregon, started to welcome the study’s 400 participants in April 2024. The primary outcomes for both partners are physical functioning and anxiety. Secondary outcomes are physical and mental symptoms, sexual function, sleep, and C-reactive protein. More details at clinicaltrials.gov

Sakach said she was “excited” to see the results of this study. “The focus on the benefits of exercise and mental health interventions is completely underutilized and underrepresented in our clinical-trial space, yet [is] so critical and often just as effective as pharmaceutical interventions for symptom management and improvement in the quality of life for our patients,” Sakach said.

Early-stage breast cancer (stages I, II, III) treated with neo/adjuvant chemotherapy within the previous 12 months. Postmenopausal women with this type of breast cancer could enroll in a randomized, double-blind, National Cancer Institute phase 2 trial to see whether exercise training plus a bioactive plant polyphenol called fisetin can prevent frailty in breast cancer survivors. For approximately 4 months, two groups of participants will take oral fisetin for 3 days out of every 14. One of these groups will receive a handout on exercise, while the other women will participate in tailored, supervised exercise training, consisting of 30-45 minutes of aerobic training and 20-30 minutes of resistance training, three times a week. A third group of individuals will receive an oral placebo and the exercise handout, while the fourth will take a placebo along with the exercise program. The UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, plans to start recruiting 164 people in July 2024. Change in the 6-minute walk distance is the primary outcome. OS over 3 years and QoL are secondary outcomes. More details at clinicaltrials.gov

“Trial designs such as this one, focused on harnessing the effect of already commercially available supplements or previously approved therapies, are super important as we try to improve outcomes for our patients with breast cancer through a whole-body approach,” said Sakach.

Metastatic hormone receptor–positive/HER2-low breast cancer previously treated with trastuzumab deruxtecan. Adults facing this scenario may join a phase 2, open-label sequencing study to discover how well they respond to another ADC, trastuzumab govitecan, after failing on trastuzumab deruxtecan (Enhertu). With the growing number of ADCs, studies like this are needed to assist physicians to sequence the drugs most effectively. Participants in the study will receive sacituzumab govitecan by IV infusion weekly, 2 weeks out of every 3, until disease progression or unacceptable toxicity, anticipated to be within 2.5 years or less. Miami Cancer Institute in Miami, started seeking the trial’s 75 participants in June 2024; sites in California and Georgia are being considered. Overall response rate is the primary outcome; OS and QoL are secondary outcomes. More details at clinicaltrials.gov

All trial information is from the National Institutes of Health’s National Library of Medicine (online at clinicaltrials.gov).

Sakach declared no conflicts of interest, and her center was not involved in any of the studies on which she commented.