Safety Results of Phase 2 Study of Bintrafusp plus Chemotherapy in Advanced NSCLC (INTR@PID LUNG 024)
In patients with advanced squamous non–small-cell lung cancer (NSCLC), the combination of bintrafusp alfa and chemotherapy was well tolerated. The most common treatment-related adverse events were anemia, nausea, and pruritus.
Bintrafusp alfa is a first-in-class bifunctional fusion protein that is composed of the extracellular domain of the TGF-βRII receptor, a TGF-β “trap,” fused to a human IgG1 monoclonal antibody blocking PD-L1. The global, phase 1b/2 INTR@PID LUNG 024 study combines bintrafusp alfa with chemotherapy in patients with stage IV non–small-cell lung cancer (NSCLC). At the American Association of Cancer Research Annual Meeting 2021, researchers reported cumulative safety data. This was the first report of safety results from a clinical study with bintrafusp alfa given via the 2400-mg every-3-weeks regimen.1
Adults with stage IV nonsquamous or squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were included in INTR@PID LUNG 024. In cohorts A, B, and C of this study, patients must not have received prior systemic therapy. In cohort D, patients had progressed on previous anti–PD-(L)1 therapy.1
Patients received intravenous bintrafusp alfa 2400 mg every 3 weeks in combination with chemotherapy for 4 cycles. In cohort A (nonsquamous only), chemotherapy consisted of cisplatin or carboplatin + pemetrexed. In cohort B, chemotherapy consisted of carboplatin + nab-paclitaxel or paclitaxel. In cohort C, chemotherapy consisted of cisplatin or carboplatin + gemcitabine. In cohort D, docetaxel was used. Treatment was then followed by bintrafusp alfa maintenance (monotherapy or combination with pemetrexed in cohort A) for up to 31 cycles.1
The primary objective of this study was to evaluate the safety of bintrafusp alfa in combination with chemotherapy. The occurrence of dose-limiting toxicities (DLTs) was assessed during a 3-week observation period.1
As of October 7, 2020, 64 patients received bintrafusp alfa in combination with chemotherapy. Of the 35 patients included in the DLT analysis, 4 experienced 1 DLT according to the safety monitoring committee (cohort A: N = 1 of 8; cohort B: N = 1 of 8; cohort C: N = 0 of 8; cohort D: N = 2 of 11). The most common (≥50%) treatment-emergent adverse events in any cohort were anemia (cohort B: 56%; cohort C: 100%; cohort D: 75%), nausea (cohort A: 53%, cohort C: 67%), pruritus (cohort C: 67%), asthenia (cohort C: 56%; cohort D: 58%), neutropenia (cohort C: 56%), decreased appetite (cohort D: 50%), and diarrhea (cohort D: 50%).1 Skin lesions, including actinic keratosis, hyperkeratosis, and keratoacanthoma, were reported in this study (cohort A: 6%; cohort C: 44%; cohort D: 8%).1
Researchers concluded that bintrafusp alfa 2400 mg every 3 weeks in combination with chemotherapy was well tolerated. No new safety signals were identified.1
1. Rolfo C, Greillier L, Veillon R, et al. Bintrafusp alfa in combination with chemotherapy in patients with stage IV NSCLC: safety results of the INTR@PID LUNG 024 study. Presented at: American Association of Cancer Research Annual Meeting 2021; April 10-15, 2021. Abstract CT104.