Abstract CT095: Phase 1 evaluation of triple therapy with boserolimab (anti-CD27 agonist), pembrolizumab, and chemotherapy in patients with triple-negative breast cancer (TNBC) with PD-L1 combined positive score (CPS) &lt;10: Safety, antitumor activity, and association between biomarkers and response
Authors: Rojas Carlos , de Spéville Bernard Gaston Doger , Im Seock-Ah , Shapira-Frommer Ronnie , De Miguel María , Cortijo Lucía González , Marin Margarita Romeo , de Jonge Maja , Ayers Mark , Zhang Yiwei , Zhai Song , Chartash Elliot , Dobrenkov Konstantin , Sohn Joohyuk 
Published: April 2024

Abstract
Background: Pembrolizumab (pembro) plus chemotherapy (chemo) is an approved therapy for patients (pts) with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) based on results from KEYNOTE-355. However, there is unmet need for effective treatment options in pts with PD-L1 CPS &lt;10. In a first-in-human, open-label, phase 1 study (NCT03396445), treatment with escalating doses of the humanized anti-CD27 agonist boserolimab (MK-5890) alone and with pembro had acceptable safety and preliminary evidence of antitumor activity in pts with advanced solid tumors. We report results for a dose-expansion cohort of this study in pts with metastatic TNBC and PD-L1 CPS &lt;10 tumors who received first-line triple therapy with boserolimab, pembro, and chemo. Exploratory analyses in this cohort assessed the association of baseline T-cell-inflamed gene expression profile (TcellinfGEP) and tumor mutational burden (TMB) with ORR.
Methods: This dose-expansion cohort enrolled pts aged ≥18 y with previously untreated locally recurrent inoperable or metastatic TNBC, measurable disease per RECIST v1.1, ECOG PS of 0/1, and tumors expressing PD-L1 at the cutoff of CPS &lt;10 per PD-L1 IHC 22C3 pharmDx (local or central testing). Pts received boserolimab 30 mg IV Q6W plus pembro 400 mg IV Q6W for 18 cycles plus nab-paclitaxel 100 mg/m2 (3 weeks on [days 1, 8, and 15]/1 week off). Primary objectives were safety/tolerability. A secondary objective was ORR per RECIST v1.1 by investigator assessment. Baseline TcellinfGEP was assessed using the NanoString PCI assay (N=31); TMB was assessed using the Illumina TSO500 mutational panel assay (N=21).
Results: 41 pts were enrolled in the dose-expansion cohort. Median study follow-up at data cutoff (Apr 25, 2023) was 11.1 (range, 2.2-20.5) mo. The most common treatment-related AEs were fatigue (51.2%), pruritus (51.2%), and alopecia (46.3%). Grade 3/4 treatment-related AEs occurred in 56.1% of pts (23/41); no grade 5 treatment-related AEs occurred. 9.8% of pts (4/41) discontinued ≥1 study treatment due to treatment-related AEs. Confirmed ORR was 46.3% (95% CI, 30.7%-62.6%), with 2 CRs and 17 PRs; 14 pts had SD, 5 had PD, and 3 had no postbaseline assessment at data cutoff. Median PFS was 10.3 (95% CI, 4.2-not reached) mo. No clear association between TcellinfGEP or TMB and confirmed ORR was observed; responses were observed in pts with non-TcellinfGEP-high (less than −0.318) and non-TMB-high (&lt;10 mut/Mb) tumors.
Conclusions: In pts with TNBC and tumors expressing PD-L1 at the cutoff of CPS &lt;10, triple therapy with boserolimab, pembro, and chemo had acceptable safety and showed preliminary evidence of antitumor activity regardless of baseline TcellinfGEP expression or TMB status.
Citation Format: Carlos Rojas, Bernard Gaston Doger de Spéville, Seock-Ah Im, Ronnie Shapira-Frommer, María De Miguel, Lucía González Cortijo, Margarita Romeo Marin, Maja de Jonge, Mark Ayers, Yiwei Zhang, Song Zhai, Elliot Chartash, Konstantin Dobrenkov, Joohyuk Sohn. Phase 1 evaluation of triple therapy with boserolimab (anti-CD27 agonist), pembrolizumab, and chemotherapy in patients with triple-negative breast cancer (TNBC) with PD-L1 combined positive score (CPS) &lt;10: Safety, antitumor activity, and association between biomarkers and response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT095.