Nammi Therapeutics has commenced a phase 1 clinical trial (NCT06582017) to investigate QXL138AM, a novel masked immunocytokine, in patients with locally advanced unresectable and/or metastatic solid tumors and multiple myeloma. The first patient has been dosed in this first-in-human study.
QXL138AM is designed with a masked interferon alpha 2 fused to an antibody targeting the CD138 protein found on tumor cells. The agent previously received orphan drug designation from the FDA for pancreatic cancer. The trial is an open-label, multicenter study that will enroll approximately 100 patients with advanced CD138-expressing cancers to evaluate the agent's safety, pharmacokinetics (PK), and preliminary activity.
Mechanism of Action
According to Dennis Kim, MD, chief medical officer for the study, QXL138AM leverages Nammi's masked immunocytokine technology to mitigate the systemic toxicity associated with interferon alpha 2. The antibody component of QXL138AM anchors the molecule to the surface of tumor cells, where proteases can remove the mask and activate the interferon alpha 2, potentially widening the therapeutic window.
Trial Design and Endpoints
The phase 1 trial is structured in two parts. Part A will focus on evaluating the safety and tolerability of QXL138AM at escalating doses, with secondary endpoints including PK and immunogenicity. Part B involves dose-expansion in three cohorts: two solid tumor indications with high CD138 prevalence and one cohort for multiple myeloma. The primary endpoints for Part B are safety and tolerability, while secondary endpoints will assess antitumor activity.
Eligibility Criteria
Patients with solid tumors eligible for enrollment must have a histopathologically confirmed diagnosis of advanced, unresectable, or metastatic ovarian, pancreatic, urothelial, renal, hepatocellular, gastrointestinal, lung, prostate, or breast cancer. These patients must have experienced disease progression despite standard therapies or have tumors for which conventional treatments are ineffective or intolerable. They also must lack alternative therapeutic options known to provide clinical benefit for their specific tumor type.
Patients with multiple myeloma must have experienced disease progression despite standard therapies or have tumors for which conventional treatments are ineffective or intolerable, as determined by the investigator. Furthermore, all patients must have failed at least three prior myeloma treatments and should have previously been treated with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38–directed therapy.
Additional eligibility criteria include being 18 years or older, having an ECOG performance status of 0, 1, or 2, having at least one measurable lesion by RECIST version 1.1, adequate organ function and bone marrow reserve, and adequate cardiac function.
Study Locations and Timeline
The study is being conducted at multiple investigator sites across the US, with an estimated completion date of May 30, 2028.
Drew W. Rasco, MD, associate director at The START Center for Cancer Research in San Antonio, TX, expressed enthusiasm for the trial, stating, "We believe that there is significant potential with Nammi's immunocytokine technology in the treatment of multiple cancer types, and we look forward to working with the Nammi team to develop this new therapy over the coming years."
