TROPION-Lung04: Phase 1b, multicenter study of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy ± carboplatin in advanced/metastatic non-small cell lung cancer (mNSCLC).

Abstract

TPS3158 Background: Datopotamab deruxtecan (Dato-DXd) is a TROP2-directed antibody drug conjugate that has shown encouraging preliminary activity and safety in patients (pts) with lung or breast cancers. The TROPION-Lung04 study was designed to assess the safety, tolerability, and antitumor activity of Dato-DXd in combination with immunotherapy ± carboplatin in pts with advanced or metastatic NSCLC. Methods: TROPION-Lung04 (NCT04612751) is a Phase 1b, multicenter, open-label, 2-part, dose escalation/confirmation and expansion study in ≈232 pts without actionable genomic alterations. In Part 1 (dose escalation/confirmation), pts will be enrolled to 1 of up to 11 cohorts. Details of cohorts 1–4 (Dato-DXd [4 or 6 mg/kg] + durvalumab [1120 mg Q3W] ± up to 4 cycles of carboplatin [AUC 5] Q3W) were previously described (Borghaei H, et al. JTO 2021;16(10):S1098-S1099). Cohorts 5–11 were recently added to evaluate Dato-DXd in combination with bispecific immunotherapies AZD2936 (anti-PD-1/TIGIT) and MEDI5752 (anti-PD-1/CTLA-4) in treatment-naïve pts. Pts in cohorts 5–8 will receive Dato-DXd (4 or 6 mg/kg) + AZD2936 ± carboplatin; pts in cohorts 9–11 will receive Dato-DXd + MEDI5752 ± carboplatin. Cohorts 5 and 6 will recruit pts with PD-L1 tumor proportion score (TPS) ≥50% in Parts 1 and 2A, and PD-L1 TPS 1–49% in Part 2B. Cohorts 7–11 will recruit pts with PD-L1 TPS < 50% only. Dose confirmation in Cohorts 5–11 will be guided by an mTPI-2 design where a minimum of 6 and a maximum of 9 pts will be assessed for dose-limiting toxicities (DLTs) during Cycle 1; if the DLT incidence meets prespecified toxicity criteria, Part 2 dose expansions may be opened. Pts may continue Dato-DXd or immunotherapy treatment until disease progression (per RECIST v1.1) or unacceptable toxicity. Study endpoints are shown in the table. Enrolment across all combination cohorts is ongoing. Clinical trial information: NCT04612751 . [Table: see text]