Abstract CT104: Bintrafusp alfa in combination with chemotherapy in patients with stage IV NSCLC: safety results of the INTR@PID LUNG 024 study
Authors: Rolfo Christian , Greillier Laurent , Veillon Remi , Badin Firas , Ghiringhelli Francois , Isambert Nicolas , Paulus Astrid , Lambrechts Marc , Grenga Italia , You Xiaoli , Koenig Andre , Hiret Sandrine 
Published: July 2021

Abstract
Background: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. The global, phase 1b/2 INTR@PID LUNG 024 (NCT03840915) study evaluates bintrafusp alfa in combination with chemotherapy (CT) in patients with stage IV NSCLC. Here we report cumulative safety, which represents the first report of safety results from a clinical study with a bintrafusp alfa 2400-mg every-three-weeks (Q3W) regimen.
Methods: Adults with stage IV nonsquamous or squamous NSCLC and an ECOG PS ≤1 are included. In cohorts A, B, and C, patients must not have received prior systemic therapy; in cohort D, patients must have had progression on previous anti-PD-(L)1 therapy. Patients received bintrafusp alfa 2400 mg Q3W intravenously in combination with CT for 4 cycles (A [nonsquamous only]: cisplatin or carboplatin + pemetrexed; B: carboplatin + nab-paclitaxel or paclitaxel; C: cisplatin or carboplatin + gemcitabine; D: docetaxel) followed by bintrafusp alfa maintenance (monotherapy or combination with pemetrexed in cohort A) for up to 31 cycles. The occurrence of dose-limiting toxicities (DLTs) was assessed during a 3-week observation period. The primary objective of this study was to evaluate the safety of bintrafusp alfa in combination with CT. Additionally, in cohort A, patients from the safety and expansion parts will be assessed for preliminary efficacy.
Results: As of October 7, 2020, 64 patients received bintrafusp alfa in combination with CT. Of the 35 patients included in the DLT analysis, 4 experienced 1 DLT according to the safety monitoring committee (A: n=1/8; B: n=1/8; C: n=0/8; D: n=2/11). The cumulative safety is reported (Table).
Conclusions: The combination of bintrafusp alfa 2400 Q3W in combination with CT was well tolerated. No new safety signals were identified.
Cohort A (n=34)Cohort B (n=9)Cohort C (n=9)Cohort D (n=12)Treatment-emergent adverse events, n (%)Any*34 (100.0)9 (100.0)9 (100.0)12 (100.0)Grade ≥324 (70.6)6 (66.7)7 (77.8)12 (100.0)Grade ≥412 (35.3)3 (33.3)5 (55.6)6 (50.0)Serious22 (64.7)3 (33.3)6 (66.7)9 (75.0)Leading to death3 (8.8)1 (11.1)00Leading to dose reduction of CT9 (26.5)2 (22.2)5 (55.6)4 (33.3)Leading to permanent discontinuation of bintrafusp alfa12 (35.3)04 (44.4)4 (33.3)Leading to permanent discontinuation of CT13 (38.2)1 (11.1)4 (44.4)3 (25.0)Treatment-related adverse events, n (%)Any bintrafusp alfa-related adverse events28 (82.4)9 (100.0)9 (100.0)12 (100.0)Bintrafusp alfa-related serious adverse events9 (26.5)01 (11.1)3 (25.0)Bintrafusp alfa-related adverse events leading to death0000Any chemotherapy-related adverse events31 (91.2)8 (88.9)9 (100.0)12 (100.0)Chemotherapy-related serious adverse events10 (29.4)1 (11.1)4 (44.4)7 (58.3)Chemotherapy-related adverse events leading to death0000Adverse events of special interest, n (%)Skin lesions†2 (5.9)04 (44.4)1 (8.3)Immune-related adverse event15 (44.1)3 (33.3)5 (55.6)6 (50.0)Infusion-related reaction3 (8.8)1 (11.1)1 (11.1)1 (8.3)Anemia16 (47.1)5 (55.6)9 (100.0)9 (75.0)*Most common (≥50%) treatment-emergent adverse events in any cohort included anemia (cohort B: 55.6%; cohort C: 100.0%; cohort D: 75.0%), nausea (cohort A: 52.9%, cohort C: 66.7%), pruritus (cohort C: 66.7%), asthenia (cohort C: 55.6%; cohort D: 58.3%), neutropenia (cohort C: 55.6%), decreased appetite (cohort D: 50.0%), and diarrhea (cohort D: 50.0%).†Defined as actinic keratosis, basal cell carcinoma, Bowen's disease, hyperkeratosis, keratoacanthoma, lip squamous cell carcinoma, and squamous cell carcinoma of skin. Actinic keratosis, hyperkeratosis, and keratoacanthoma were reported in this study.
Citation Format: Christian Rolfo, Laurent Greillier, Remi Veillon, Firas Badin, Francois Ghiringhelli, Nicolas Isambert, Astrid Paulus, Marc Lambrechts, Italia Grenga, Xiaoli You, Andre Koenig, Sandrine Hiret. Bintrafusp alfa in combination with chemotherapy in patients with stage IV NSCLC: safety results of the INTR@PID LUNG 024 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT104.