A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas

Abstract

This phase I trial evaluated the safety, tolerability, and preliminary activity of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas. Nineteen patients received at least one dose of both study drugs. Dose-limiting toxicities consisted of thrombocytopenia, hypertriglyceridemia, oral mucositis, clinical deterioration, and the inability to receive at least three doses of temsirolimus during cycle 1. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (n = 8), neutropenia (n = 5), and two patients each hyperphosphatemia, lymphopenia, and hypertriglyceridemia. The recommended phase II dose was inotuzumab ozogamicin 0.8 mg/m² on day 1 in combination with temsirolimus 10 mg on days 8, 15, and 22 every 28 days. Among 18 patients evaluable, seven (39%) with follicular lymphoma had a partial remission. This drug combination is not possible within a therapeutically useful range of doses due to toxicities. Antitumor activity was observed in heavily pretreated patients (ClinicalTrials.gov, Identifier NCT01535989).

Keywords:

• Phase I trial
• inotuzumab ozogamicin
• temsirolimus
• non-Hodgkin lymphomas

Disclosure statement

M. C. Pirosa, L. Zhang, F. Hitz, D. Hess, U. Novak, T. Terrot, M. Pascale, and L. Mazzucchelli declares no conflict of interest. F. Bertoni declares institutional research funds from Acerta, ADC Therapeutics, Bayer AG, Cellestia, CTI Life Sciences, EMD Serono, Helsinn, ImmunoGen, Menarini Ricerche, NEOMED Therapeutics 1, Nordic Nanovector ASA, Oncology Therapeutic Development, PIQUR Therapeutics AG, consultancy fee from Helsinn, Menarini and travel grants from Amgen, Astra Zeneca, Jazz Pharmaceuticals, PIQUR Therapeutics AG. F. Cavalli declares no conflict of interest. E. Zucca declares that he is a participant of the advisory committees of Abbvie, Beigene, Celgene, Celltrion Healthcare, Incyte, Janssen, Kite, Merck, Roche and has received institutional research funding from AstraZeneca, Celgene, Janssen, and Roche. A. Stathis declares Consultancy services to Bayer, Eli Lilly; institutional research funding from Pfizer, ADC Therapeutics, Bayer, Roche, Merck, Novartis, MEI Therapeutics, and Abbvie; travel grants from Abbvie and PharmaMar.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all individual participants included in the study.

Additional information

Funding

The trial was funded by Pfizer, which also provided the two drugs.