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Dr Timothy Yap: Rucaparib/Sacituzumab Govitecan Combo Effective Against Triple-Negative Disease


A novel combination shows promise against advanced solid tumors, including triple-negative breast cancer, noted Timothy A. Yap, MBBS, PhD, FRCP, medical director of the Institute for Applied Cancer Science at MD Anderson Cancer Center.

Advanced solid tumors responded favorably to the combination of rucaparib plus sacituzumab govitecan, according to results of the phase 1B SEASTAR study presented at this year’s virtual European Society for Medical Oncology (ESMO) meeting by Timothy A. Yap, MBBS, PhD, FRCP, medical director, Institute for Applied Cancer Science; associate professor, Department of Investigational Cancer Therapeutics (Phase I Program), Department of Thoracic/Head and Neck Medical Oncology; and associate director of Translational Research, Khalifa Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center.


Tell us about the SEASTAR study and the data you presented at ESMO on triple-negative breast cancer.

The arm of the phase 1B/phase 2 SEASTAR study that I presented at ESMO evaluated a novel combination of the PARP inhibitor rucaparib with sacituzumab govitecan, which is a TROP2-directed antibody conjugated to a topoisomerase 1 inhibitor, SN-38, that we conducted in patients with advanced solid tumors. This is the first presentation of these data of this novel combination.

And so in this trial, patients with metastatic triple-negative breast cancer were indeed included in this phase 1B part of the study, as were patients with other advanced or metastatic solid tumors, such as platinum-resistant ovarian cancer and also urothelial cancers. This first presentation of data from the phase 1B portion of the SEASTAR study showed very encouraging signals of antitumor activity.

The antitumor activity was observed with the combination in patients with different solid tumors, including patients with prior PARP inhibitor exposure and also those without a deleterious homologous recombination repair gene mutation. Despite early toxicities, including dose limiting and neutropenia in 2 out of 3 patients at the higher dose level, all 6 patients continued treatment for at least 12 weeks, with treatment-related toxicities effectively managed with dose modifications and/or growth factor support.

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