Bothell, Washington-based Immunome, Inc. (Nasdaq: IMNM) has dosed the first patient in a Phase I first-in-human study of IM-1617, an antibody-drug conjugate directed at an undisclosed receptor tyrosine kinase (RTK) and armed with HC74, the company's proprietary topoisomerase I inhibitor payload. The trial's significance lies partly in its target biology: the RTK in question is described as promoting tumor cell survival while simultaneously mediating immune cell exclusion — a dual role that, if confirmed clinically, could position IM-1617 as relevant in immunologically cold tumors where checkpoint inhibitors have largely failed.
The open-label, multicenter dose escalation and expansion study will enroll patients with advanced solid tumors, including colorectal cancer, non-small cell lung cancer, and breast cancer. Primary objectives cover safety, tolerability, and pharmacokinetics, with preliminary anti-tumor activity as an exploratory endpoint. Immunome has not disclosed enrollment targets or an anticipated completion date. Two additional ADC candidates — IM-1340 and IM-1335 — are expected to reach IND submission by mid- and late 2026, respectively, signaling broader platform ambitions beyond this single asset.
The rationale for IM-1617 rests on a well-documented but therapeutically underexploited observation: certain receptor tyrosine kinases do not merely sustain tumor cell proliferation but actively remodel the tumor microenvironment to prevent T-cell infiltration. The TAM family RTKs — TYRO3, AXL, and MERTK — are the best-characterized examples, functioning as innate immune checkpoints that suppress dendritic cell and macrophage activity while driving tumor cell survival through PI3K/AKT and RAS/MAPK signaling. AXL in particular has been directly implicated in T-cell exclusion in breast cancer models, where high AXL expression correlated with complete absence of immune infiltration even following radiotherapy.
This biology is directly relevant to the three indications Immunome has identified. Approximately 85% of colorectal cancers are microsatellite-stable and immunologically cold, explaining why PD-1/PD-L1 inhibitors have shown no benefit in this population. A comparable subset of non-small cell lung cancers and triple-negative breast cancers similarly fail to respond to immunotherapy, not because of absent antigenicity but because immune cells are physically excluded from the tumor parenchyma. An ADC targeting the RTK responsible for that exclusion could, in principle, simultaneously kill antigen-expressing tumor cells and relieve the suppressive barrier — potentially rendering surviving tumor tissue more susceptible to endogenous or therapeutically induced immune responses.