Phase 1 AQUA07 allosteric ALK inhibitor (macrocyclic peptide) alone or with lorlatinib in ALK-positive NSCLC

Chugai Pharmaceutical is running this first-in-human, open-label, multicenter Phase 1 study of AQUA07 alone and in combination with lorlatinib in advanced or metastatic ALK-positive NSCLC. Separate dose-escalation paths evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and early antitumor activity to establish appropriate doses. Participants must have received a prior ALK tyrosine kinase inhibitor; treatment with crizotinib alone does not satisfy that requirement.

Chugai has described AQUA07 as an orally administered macrocyclic peptide that binds an allosteric site on ALK rather than the ATP-binding pocket used by established ALK inhibitors. Pairing it with Pfizer’s lorlatinib therefore tests two different binding approaches, with the aim of extending targeted control after resistance. Whether this translates into better resistance coverage or an acceptable combination safety profile remains to be established clinically. Current treatment choices depend on prior ALK inhibitors and resistance findings, with platinum/pemetrexed chemotherapy an important option after targeted therapy; checkpoint immunotherapy is not a routine substitute for effective ALK-directed treatment.