TACTI-004: A double-blinded, randomized phase 3 trial in patients with advanced/metastatic non-small cell lung cancer receiving eftilagimod alfa (MHC class II agonist) in combination with pembrolizumab (P) and chemotherapy (C) versus placebo + P + C.
Background: Eftilagimod alfa (E), an antigen presenting cell activator, binds to a subset of MHC class II molecules to mediate T cell (CD4/CD8) recruitment/activation. Prior studies in first line (1L) non-small cell lung cancer (NSCLC) (TACTI-002 [NCT03625323]: combining E + pembrolizumab (P); INSIGHT-003 [NCT03252938] combining E with chemotherapy + P [SoC]) showed encouraging efficacy results across all PD-L1 strata & excellent safety profiles. TACTI-004 is a double-blinded, randomized, placebo-controlled phase 3 study testing E + SoC vs. placebo + SoC in 1L NSCLC patients (pts). Methods: Approximately 756 pts with 1L NSCLC will be enrolled, irrespective of PD-L1 status, & randomized 1:1 to receive either E + SoC or placebo + SoC. The dual primary endpoint (EP) is overall survival & progression-free survival (RECIST 1.1). Secondary EPs include ORR, disease control rate, duration of response, quality of life, safety & biomarkers. Pts will receive 30 mg E SC q2w for 24 weeks, then q3w and P IV at 200 mg (30 min) q3w; both treatments for up to 2 yrs. Chemotherapy choice will be histology-dependent: non-squamous NSCLC pts will receive IV cisplatin (75 mg/m2) or carboplatin (AUC 5 or 6) + pemetrexed (500 mg/m2) q3w for 3 mo, then maintenance pemetrexed q3w. Squamous NSCLC pts will receive carboplatin (AUC 5 or 6) + paclitaxel (175 or 200 mg/m2) q3w for 3 mo. Imaging will be performed q6w until week 18, q9w until week 54 & q12w thereafter. Testing for PD-L1 (22C3) & genetic alterations will be prospectively assessed. Key inclusion criteria: Adults diagnosed with measurable advanced/metastatic (A/M) NSCLC (squamous or non-squamous), not amenable to curative treatment nor locally available oncogenic driver mutation-based 1L therapy. Treatment-naïve for systemic therapy (previous palliative radiotherapy for A/M disease acceptable). Expected survival >3 months & ECOG 0 or 1. Tumour tissue must be available for PD-L1 central testing. Pts may not have tumours with EGFR mutations nor ALK or ROS1 translocations. Stable brain metastasis is acceptable.
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