Unknown

Dataset Information

0

Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells.


ABSTRACT: Purpose: Little prospective data are available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiotherapy (SABR) with ipilimumab.Experimental Design: SABR was given either concurrently (1 day after the first dose) or sequentially (1 week after the second dose) with ipilimumab (3 mg/kg every 3 weeks for 4 doses) to five treatment groups: concurrent 50 Gy (in 4 fractions) to liver; sequential 50 Gy (in 4 fractions) to liver; concurrent 50 Gy (in 4 fractions) to lung; sequential 50 Gy (in 4 fractions) to lung; and sequential 60 Gy (in 10 fractions) to lung or liver. MTD was determined with a 3 + 3 dose de-escalation design. Immune marker expression was assessed by flow cytometry.Results: Among 35 patients who initiated ipilimumab, 2 experienced dose-limiting toxicity and 12 (34%) grade 3 toxicity. Response outside the radiation field was assessable in 31 patients. Three patients (10%) exhibited partial response and 7 (23%) experienced clinical benefit (defined as partial response or stable disease lasting ?6 months). Clinical benefit was associated with increases in peripheral CD8+ T cells, CD8+/CD4+ T-cell ratio, and proportion of CD8+ T cells expressing 4-1BB and PD1. Liver (vs. lung) irradiation produced greater T-cell activation, reflected as increases in the proportions of peripheral T cells expressing ICOS, GITR, and 4-1BB.Conclusions: Combining SABR and ipilimumab was safe with signs of efficacy, peripheral T-cell markers may predict clinical benefit, and systemic immune activation was greater after liver irradiation. Clin Cancer Res; 23(6); 1388-96. ©2016 AACR.

SUBMITTER: Tang C 

PROVIDER: S-EPMC5355002 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells.

Tang Chad C   Welsh James W JW   de Groot Patricia P   Massarelli Erminia E   Chang Joe Y JY   Hess Kenneth R KR   Basu Sreyashi S   Curran Michael A MA   Cabanillas Maria E ME   Subbiah Vivek V   Fu Siqing S   Tsimberidou Apostolia M AM   Karp Daniel D   Gomez Daniel R DR   Diab Adi A   Komaki Ritsuko R   Heymach John V JV   Sharma Padmanee P   Naing Aung A   Hong David S DS  

Clinical cancer research : an official journal of the American Association for Cancer Research 20160920 6


<b>Purpose:</b> Little prospective data are available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiotherapy (SABR) with ipilimumab.<b>Experimental Design:</b> SABR was given either concurrently (1 day after the first dose) or sequentially (1 week after the second dose) with ipilimumab (3 mg/kg every 3 weeks for 4 doses) to five treatment groups: concurrent 50 Gy (in 4 fraction  ...[more]

Similar Datasets

| S-EPMC6349603 | biostudies-literature
| S-EPMC6364565 | biostudies-literature
| S-EPMC8498727 | biostudies-literature
| S-EPMC5812885 | biostudies-literature
| S-EPMC9090939 | biostudies-literature
| S-EPMC4018668 | biostudies-literature
| S-EPMC6891218 | biostudies-literature
| S-EPMC9743639 | biostudies-literature
| S-EPMC8575366 | biostudies-literature
| S-EPMC7647381 | biostudies-literature