Abstract CT162: The phase 1b PORTIA study: Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL)

Introduction: Pembrolizumab (pembro) has shown clinical activity in r/r DLBCL after failing tisagenlecleucel (tisa), an autologous anti-CD19 chimeric antigen receptor (CAR)-T therapy (Chong et al. Blood. 2017). Methods: PORTIA is a phase 1b, multicenter, open-label trial investigating the safety and efficacy of tisa plus pembro in adult patients (pts) with r/r DLBCL. Pts receive a single tisa IV infusion (target: 0.6-6.0×108 cells) on Day (D)1 and pembro at 200mg every 21 days, for up to 6 doses. Pembro was started on D15 post tisa in Cohort 1, with the option of moving to D8 (Cohort 2) or D22 based on safety profile and dose-limiting toxicities (DLTs). Primary endpoints: proportion of pts receiving pembro per schedule, incidence of DLTs (dose-timing selection phase), overall response rate (dose-expansion phase). Results: As of 5 March 2019, 5 patients were screened for Cohort 1; 4 pts were enrolled. Median age was 54 (range, 35-79). Median follow-up after tisa infusion was 46 days (range, 36-85). Pts received 1.7-3.0×108 CAR-positive T cells and 1, 2, 2, and 4 pembro doses, respectively, with no delays. All 4 pts experienced ≥1 adverse event (AE), with no exacerbation or recurrence of tisa-related AEs post pembro infusion. No pembro-related AEs, DLTs or grade 3/4 treatment-related AEs (TRAEs) were observed (Table 1). All pts experienced initial expansion between D6-15 post-tisa infusion; overall exposure is consistent with that observed in the JULIET trial. Two pts discontinued pembro treatment (after 1 and 2 doses, respectively) due to disease progression. With limited follow-up, 1 partial response has been observed. Conclusions: PD-1 blockade with pembro was feasible and showed a manageable safety profile in the first 4 pts. No DLTs or clinically significant exacerbation of AEs were observed. Efficacy and safety data for Cohorts 1 and 2 (D15 and D8) with longer follow-up will be presented at the congress. Clinical trial information:NCT03630159 Citation Format: Ulrich Jaeger, Nina Worel, Joseph P. McGuirk, Peter A. Riedell, Isabelle Fleury, Peter Borchmann, Simon Newsome, Ahmed M. Abdelhady, Alessandra Forcina, Lida Bubuteishvili Pacaud, Edmund K. Waller. The phase 1b PORTIA study: Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT162.