2021 Pipeline Updates: Promising Ongoing Trials in Breast Cancer From TROP2 ADCs to Oncolytic Viruses


CancerNetwork® looks back on some of the promising, ongoing pieces of clinical research within the breast cancer space from 2021.

A plethora of clinical trials in the breast cancer space have launched throughout 2021, leaving much to look forward to in the new year and beyond. In part 2 of a 3-part series examining clinical cancer research coming down the oncology pipeline, CancerNetwork® delves into several breast cancer studies promising that launched this year, including research on a TROP2-directed antibody-drug conjugate (ADC), a PI3K/mTOR inhibitor, and a first-in-human trial assessing a cancer-killing oncolytic virus.

Don’t forget to read part 1 of our oncology pipeline series where we examine several studies in the non–small cell lung cancer space.

TROPION-Breast01 Assesses a New Possibility for HR+, HER2- Breast Cancer

Recently, the first patient with hormone receptor (HR)–positive, HER2-negative inoperable or metastatic breast cancer was dosed with datopotamab deruxtecan (DS-1062a; dato-DXd) as part of the phase 3 TROPION-Breast01 trial (NCT05104866).1 The TROP2-directed DXd ADC that is currently being developed by Daiichi Sankyo and AstraZeneca is currently under investigation in the global, randomized, open-label trial at a dose of 6 mg/kg vs investigator’s choice of chemotherapy. Chemotherapy options include eribulin, capecitabine, vineorbelbine, or gemcitabine.

“There are no TROP2-directed therapies currently approved for HR-positive, HER2-negative breast cancer and we are encouraged by the emerging clinical profile of datopotamab deruxtecan in patients with breast cancer,” Gilles Gallant, BPharm, PhD, FOPQ, senior vice president and global head of oncology development, Oncology R&D at Daiichi Sankyo, said in a press release. “TROPION-Breast01 is the first pivotal trial of datopotamab deruxtecan in breast cancer and the third pivotal study in our clinical development program, underscoring our efforts to accelerate development of this TROP2-directed ADC in breast and lung cancer.”

Dato-DXd consists of a humanized anti-TROP2 IgG1 monoclonal antibody that is attached to a topoisomerase I inhibitor payload with an exatecan derivative that is executed through a tetrapeptide-based cleavable linker.

The trial has dual primary end points of progression-free survival (PFS) by blinded independent central review and overall survival, with key secondary end points including investigator assessed PFS, objective response rate, duration of response, disease control rate, and patient-reported outcomes.

TROPION-Breast01 has an estimated enrollment of roughly 700 patients who will be administered treatment in sites across Africa, Asia, Europe, and North and South America.

“Most patients with HR-positive, HER2-negative metastatic breast cancer will inevitably progress on available treatments, including hormonal therapy and standard-of-care chemotherapy. In this setting, the unmet need is high, and new therapeutic approaches are necessary to delay disease progression and extend survival,” Cristian Massacesi, MD, chief medical officer and oncology chief development officer at AstraZeneca, explained. “The TROPION-Breast01 trial will evaluate whether datopotamab deruxtecan may be a more effective treatment than chemotherapy for patients with previously treated HR-positive, HER2-negative advanced breast cancer previously treated with 1 to 2 lines of chemotherapy."

Data on dato-DXd and the TROPION-PanTumor01 trial were most recently reported at the 2021 San Antonio Breast Cancer Symposium.2 Findings from the trial indicated that after a median follow up of 7.6 months, patients in the triple-negative breast cancer (TNBC) cohort experienced an overall response rate by blinded independent central review of 34%. Additionally, 32% of patients had a complete response and 32% had partial responses. Investigators also reported a disease control rate of 77%.

Celcuity and Pfizer Collaborate on Phase 3 Palbociclib Clinical Trial

Celcuity and Pfizer have entered into a clinical trial collaboration and supply agreement, in which Pfizer provides palbociclib (Ibrance) for use in a phase 3 clinical study being conducted by Celuity at no cost to the company.3

A phase 3 clinical trial is expected to launch in the first half of 2022 assessing the use of the pan-PI3K/mTOR inhibitor gedatolisib (PF-05212384) in combination with palbociclib and fulvestrant for patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer. Celcuity will release further details about the clinical trial following discourse and subsequent feedback from the FDA.

“We are excited that Pfizer is providing palbociclib for this important phase 3 clinical trial,” said Brian Sullivan, chief executive officer and co-founder of Celcuity, said in a press release. “Our goal is to address the significant unmet need for new therapeutic options for patients who progressed on their first line of treatment for ER-positive/HER2-negative advanced breast cancer.”

Gedatolisib was most recently assessed in combination with palbociclib as part of a phase 1b trial in patients with ER-positive, HER2-negative metastatic breast cancer (NCT02626507).4 Among the 88 patients enrolled on the study, 60% of patients experienced an objective response as of the data cut-off of January 11, 2021. The combination was also found to be well tolerated, with most adverse effects (AEs) being grade 1/2. The most common grade 3/4 AEs that were related to treatment with gedatolisib included rash and stomatitis

City of Hope Launches First Clinical Trial With Oncolytic Virus as a Treatment for TNBC

A cancer-killing oncolytic virus is set to be evaluated as part of a first-in-human phase 1 clinical trial (NCT05081492) for patients with metastatic TNBC.5 The therapy, CF33-hNIS-antiPDL1, was genetically engineered from the chimeric oncolytic orthopoxvirus, which occurs naturally. CF33-hNIS-antiPDL1, the patents for which have been licensed to Imugene Limited, has been designed to infect, replicate, and kill cancer cells and ignore healthy cells.

“The study is designed to determine the safety and optimal biological dose that may induce an immune response in triple-negative breast cancer tumors,” principal investigator Yuan Yuan, MD, PhD, an associate professor of the Department of Medical Oncology & Therapeutics Research at City Hope, said in a press release. “Current approved therapies do not offer a cure for this aggressive type of breast cancer, which often becomes resistant to chemotherapy. Clinical trials like this one seek durable responses and better quality of life for patients.”

The goal of the phase 1 study is to determine the optimal dose of the virus and determine whether the therapy is safe and efficacious for this patient population. Investigators intended to enroll patients who have progressed through standard-of-care chemotherapy. Patients will be treated with between 3 cycles of treatment including 6 doses that will be injected directly into the tumor.

CF33 has notably demonstrated cancer killing properties in a number of tumor types, including pancreatic, stomach, ovarian, and colon cancer. Moreover, preclinical data have indicated that the CF33 oncolytic virus is able to boost the presence of immune checkpoint inhibitors.

“It is an exciting time in immuno-oncology. Preclinical research has shown that this oncolytic virus can direct the killing of cancers and stimulate the immune system to enable further killing of cancers,” Yuman Fong, MD, the Sangiacomo Family Chair in Surgical Oncology at City of Hope and CF33 developer, concluded. “This trial is an important step forward.”


  1. TROPION-Breast01 phase 3 trial of datopotamab deruxtecan initiated in patients with hormone receptor positive, HER2 negative metastatic breast cancer. News release. Daiichi Sankyo. November 18, 2021. Accessed December 3, 2021. https://yhoo.it/3lxyCtZ
  2. Krop I, Juric D, Shimizu T, et al. Datopotamab deruxtecan (Dato-DXd) in advanced/metastatic HER2 negative breast cancer: triple negative breast cancer results from the phase 1 TROPION-PanTumor01 study. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS1-05.
  3. Celcuity announces clinical trial collaboration and supply agreement with Pfizer to provide Ibrance(R) (palbociclib) for planned phase 3 clinical trial. News release. Accesswire. November 15, 2021. Accessed December 7, 2021. https://yhoo.it/332OCgZ
  4. Celcuity reports preliminary data from phase 1b trial of gedatolisib plus Ibrance® and endocrine therapy for patients with ER+/HER2- metastatic breast cancer and provides corporate update. News release. Celcuity. April 8, 2021. Accessed December 8, 2021. https://bit.ly/3lJWZoo
  5. City of Hope opens oncolytic virus clinical trial for patients with advanced breast cancer. News release. November 18, 2021. Accessed December 7, 2021. https://bit.ly/3rHZBXB
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