Phase I/II Study of IPH1101, γσ T Cell Agonist, Combined with Rituximab, in Low Grade Follicular Lymphoma Patients.
Authors: Laurent Guy , de Micheaux Sylvie Lafaye , Solal-Celigny Philippe , Soubeyran Pierre , Delwail Vincent , Ghesquières Hervé , Thieblemont Catherine , Jourdan Eric , Beautier Lucile , Audibert Fabien , Squiban Patrick , Sicard Helene , Rossi Jean-Francois 
Published: October 2019

Abstract 1649

Poster Board I-675

Non-conventional γσ T lymphocytes are innate immunity effectors bearing potent anti-tumoral activity, particularly against malignant B cells. IPH1101 is an agonist of γσ T cells, which in the presence of low doses of IL-2 potentiates their direct cytotoxic activity.

ADCC is a major molecular mechanism underlying rituximab's efficacy. Increasing the number and the activation state of killer lymphocytes mediating ADCC is therefore believed to be beneficial for therapeutic potency. Since γσ T cells have been found to be capable of mediating ADCC, modulating γσ T cells in the context of rituximab is worth being tested in a clinical trial. The main purpose is to assess the clinical efficacy of IPH1101 with low doses of IL-2, combined with a standard rituximab treatment, in patients (pts) with follicular lymphoma.

This is an open label, multinational study consisting of a dose escalation Phase (ph) I-like part followed by a ph II part. The ph I part has shown a good safety and immuno-biological efficacy profile for the highest dose of IL-2. Consequently, the pts of the phase II part were treated with the combination of rituximab (375 mg/m2) administered 4 times weekly, IPH1101 (750 mg/m2) administered i.v. 3 times (every 3 weeks) and IL-2 (8 MIU) administered daily s.c. for 5 days starting on the day of each IPH1101 administration.

All pts presented low grade FL which had relapsed after 1 to 4 lines of previous therapy including at least one rituximab-containing line. Inclusion criteria set forth that pts should have no lesion > 7 cm.

Results

We report here the end of recruitment and updated data on 45 patients and more than 100 cycles of IPH1101. Overall safety was good, and most of the drug-related adverse events were, as expected, flu like symptoms of grade 1 or 2. The SAEs reported were 2 hypotensions, 1 bronchospasm, 1 allergic reaction (back pain), 1 glomerular filtration decrease, 1 ALAT elevation, 1 hypertension and 1 asthenia.

The immuno-biological follow up demonstrated the very good pharmacodynamic profile of IPH1101 in these patients and these data are presented in details in another abstract from Lucas et al.

To date, in the first set of evaluable patients (12 pts) and after at least 3 months post treatment, investigators reported about 75% of response and 50% of CR. Most of the responses are already confirmed by an independent panel.

Conclusion

These observations confirm the good safety and the biological rationale of this approach. Furthermore, the response rate in this first set of pts is encouraging in the context of previously treated patients. Updated results will be presented at the meeting.

Disclosures

Laurent: Innate pharma: Honoraria. Lafaye de Micheaux:Innate Pharma: Employment. Solal-Celigny:Innate Pharma: Research Funding. Soubeyran:Innate Pharma: Research Funding. Delwail:Innate Pharma: Honoraria. Ghesquières:innate pharma: Honoraria. Thieblemont:Innate Pharma: Honoraria. Jourdan:Innate Pharma: Honoraria. Beautier:Innate Pharma: Employment. Squiban:Innate pharma: Employment. Rossi:Innate Pharma: Honoraria.