Immatics (IMTX) Study Update summary

Study design and objectives

• Phase I-A dose escalation studies evaluated IMA402 (PRAME) and IMA401 (MAGEA4/8) TCR bispecifics in patients with advanced, refractory solid tumors.

• Both agents are off-the-shelf biologics designed for broad patient access and combination potential.

• Primary objectives included safety, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) determination.

• Dose escalation followed a MABEL-based approach, with step dosing and biweekly schedules for responders.

• Phase 1a dose escalation completed for both; Phase 1b dose expansion for IMA402 initiated.

Safety and tolerability

• IMA402 showed a favorable safety profile across all doses, with no high-grade CRS or ICANS at RP2D; only one high-grade CRS event occurred at a lower step dose and was mitigated by dose adjustment.

• No IMA402-related grade 5 events or MTD reached at 30 mg; broad combination potential is supported.

• IMA401's RP2D was set at 1–2 mg due to dose-limiting neutropenia at higher doses; no ICANS observed.

• Most common adverse events were transient lymphopenia and low-grade cytokine release syndrome for both agents.

• Safety of IMA401 in combination with pembrolizumab was consistent with monotherapy.

Efficacy and clinical activity

• IMA402 achieved a 30% confirmed objective response rate (ORR) at RP2D, with deep and durable responses in melanoma and ovarian cancer.

• All confirmed responses at RP2D were ongoing at data cutoff, including two complete metabolic responses in melanoma and one 100% reduction in ovarian carcinoma.

• Tumor shrinkage observed in 55% and disease control in 65% of RP2D patients; median duration of response not reached.

• IMA401 showed 25% ORR in head and neck cancer, 29% in melanoma, and early activity in squamous NSCLC at ≥1 mg.

• All confirmed IMA401 responses lasted over 6 months, with the longest ongoing over 2 years in melanoma.