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

Reference
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.