Durvalumab Combinations in TNBC: Promising Results with D+Paclitaxel (Phase 1b/2 Study)

In patients with metastatic TNBC, chemotherapy with immune checkpoint inhibitors can enhance outcomes compared to chemotherapy alone; however, many patients still have poor clinical outcomes. BEGONIA (NCT03742102) is an ongoing, two-part, multicenter, multiarm, open-label platform study evaluating the safety and efficacy of D (anti–PD-L1)+P and DP in combination with novel therapies as a first-line (1L) treatment for metastatic TNBC. Researchers presented preliminary results from Part 1 of Arm 1, D+P, and Arm 6, D+T-DXd, an antibody-drug conjugate consisting of an anti-HER2 antibody, tetrapeptide-based cleavable linker, and topoisomerase I inhibitor payload.

Patients (pts) with untreated, irresectable, locally advanced, or metastatic TNBC were eligible. Based on local testing, patients with HER2-low–expressing tumors (IHC 2+/ISH–, IHC 1+/ISH–, or IHC 1+/ISH untested) were assigned to the D+T-DXd arm. Patients in Arm 1 received D (1500 mg IV Q4W)+P (90 mg/m2 IV Day 1, 8, 15 Q4W), while those in Arm 6 received D (1120 mg IV)+T-DXd (5.4 mg/kg IV Q3W) until progression or unacceptable toxicity. The primary goals were safety and tolerability. Objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) were secondary endpoints. Tumors were evaluated using Q8W (D+P) or Q6W (D+T-DXd) criteria. Additional patients were enlisted if D+T-DXd was well tolerated in the first 6 patients treated with it. Different eligibility requirements, treatments, and data maturation made it impossible to compare study arms.

Arm 1 D+P (data cutoff September 2020): 23 pts received D+P (7 ongoings); 2 pts discontinued D+P due to adverse events. The median follow-up period was 16.6 (8.5–19.8) months. 10 (44%) and 1 (4%) pts were allotted for AEs and SAEs of Grades 3/4. The D dose was delayed for seven (30%) patients. Confirmed ORR was 13 of 23 (57%), with 54% still responding at 12 months (median DoR was not reached). In the D+P arm, the median PFS was 7.3 (95% CI: 5.4–13.8) months. A total of 11 patients received D+T-DXd to date (all ongoing) for Arm 6 D+T-DXd (data cutoff November 2020). The median duration of follow-up was 2.3 (0–6) months. Four (36%) and one (9%) pts experienced Grade 3/4 AEs and SAEs, respectively. One patient who received D+T-DXd had a Grade 1 increase in troponin. The D dose was delayed, and the T-DXd dose was decreased for two (18%) patients. Confirmed ORR was 4/4 (100 percent; only 4 patients had the opportunity to complete 2 on-treatment disease assessments), with all 4 remaining in response (median DoR not reached).

As anticipated for a 1L TNBC IO/taxane combination, D+P exhibited an acceptable safety profile and response rate. D+T-DXd demonstrated promising early safety and efficacy in 1L HER2-low–expressing TNBC; D+T-DXd patient evaluation and enrollment are ongoing. The D+T-DXd data will be updated, and the influence of PD-L1 expression in both arms will be investigated.

Source:https://meetings.asco.org/abstracts-presentations/195748

Clinical Trial: http://clinicaltrials.gov/show/NCT03742102

Peter Schmid, Seock-Ah Im, Anne Armstrong, Yeon Hee Park, Wei-Pang Chung, Zbigniew Nowecki, Simon Lord, Piotr Jan Wysocki, Yen-Shen Lu, Hannah Dry, Vatsala Karwe, Ross Stewart, Pia Herbolsheimer, Ana Tablante Nunes, Kyung Hae Jung/BEGONIA: Phase 1b/2 study of durvalumab (D) combinations in locally advanced/metastatic triple-negative breast cancer (TNBC)—Initial results from arm 1, d+paclitaxel (P), and arm 6, d+trastuzumab deruxtecan (T-DXd)/J Clin Oncol 39, 2021 (suppl 15; abstr 1023) DOI 10.1200/JCO.2021.39.15_suppl.1023