Safety and Efficacy of Iruplinalkib for Patients with Relapsed or Refractory (r/r) ALK+ Lymphoma: A Phase II Trial

Background：

Anaplastic lymphoma kinase-positive (ALK+) lymphoma includes ALK+ anaplastic large cell lymphoma (ALCL) and ALK+ large B cell lymphoma (LBCL). ALK is a receptor tyrosine kinase in the insulin receptor superfamily. ALK inhibitor such as crizotinib exhibited significant effectiveness in relapsed or refractory (r/r) ALK+ lymphoma. Iruplinalkib, a highly selective oral ALK and c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI), has shown promising anti-tumor activity with a manageable safety profile in r/r ALK+ non-small cell lung cancer. Herein, we reported the efficacy and safety of iruplinalkib for r/r ALK+ lymphoma.

Aims:

To evaluate the efficacy and safety of iruplinalkib in patients with r/r ALK+ lymphoma.

Methods:

This prospective stage II study enrolled patients aged 18-65 years with histologically confirmed r/r ALK+ lymphoma, including the r/r ALK+ ALCL and ALK+ LBCL. The primary endpoint were overall response rate (ORR), and the secondary endpoints included complete response rate (CRR) , progression-free survival(PFS) and safety.

Results:

As of the database cutoff on July 30, 2024, 6 patients were enrolled. The median age was 39 years (range, 23-70). Three patients (50.0%) were male. Five (83.3%) patients were diagnosed with ALK+ ALCL, 1 patient (16.7%) had ALK+ LBCL. The median line of prior chemotherapy was 1 (range, 1-2).

Among 5 patients with evaluable response, the ORR was 80% with a CRR of 20.0%.One patient with ALK+ ALCL achieved complete remission, 2 with ALK+ ALCL and 1 with ALK+LBCL achieved partial remission，and 1 with ALK+ ALCL achieved stable disease. The median PFS was 2.5 months (range, 0.9-6.0 months). Serious adverse events (SAEs) were not observed in all patients. No treatment discontinuation or death due to treatment-related adverse events (TRAEs) was reported.

Summary/Conclusion:

Iruplinalkib demonstrated a tolerable safety and a good efficacy in r/r ALK+ lymphoma patients.

Keywords:Anaplastic lymphoma kinase; Iruplinalkib; Lymphoma; Therapeutics; Prognosis

No relevant conflicts of interest to declare.

Iruplinalkib, a highly selective oral anaplastic lymphoma kinase(ALK) and c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI), exhibited strong antitumor effects in crizotinib-resistant models.