Antibody has ‘very promising activity’ in rel/ref CTCL
LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.
The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).
There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.
Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.
“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”
“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”
Patients
Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).
The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.
Treatment
This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.
Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.
The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.
Safety
There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.
The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).
Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).
Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.
One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.
The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).
