Dataset Information

A phase I trial of pembrolizumab with hypofractionated radiotherapy in patients with metastatic solid tumours.

ABSTRACT:

Background

We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers.

Methods

There were two strata (12 patients each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. Patients had ≥2 lesions; only one was irradiated (8 Gy × 3 for first half; 17 Gy × 1 for second half in each stratum) and the other(s) followed for response.

Results

Of the 24 patients, 20 (83%) had treatment-related adverse events (AEs) (all grade 1 or 2). There were eight grade 3 AEs, none treatment related. There were no dose-limiting toxicities or grade 4/5 AEs. Stratum 1: two patients (of 12) with progression on prior PD-1 blockade experienced prolonged responses (9.2 and 28.1 months). Stratum 2: one patient experienced a complete response and two had prolonged stable disease (7.4 and 7.0 months). Immune profiling demonstrated that anti-PD-1 therapy and radiation induced a consistent increase in the proliferation marker Ki67 in PD-1-expressing CD8 T cells.

Conclusions

HFRT was well tolerated with pembrolizumab, and in some patients with metastatic NSCLC or melanoma, it reinvigorated a systemic response despite previous progression on anti-PD-1 therapy.

Clinical trial registration

NCT02303990 ( www.clinicaltrials.gov ).

SUBMITTER: Maity A

PROVIDER: S-EPMC6251028 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

A phase I trial of pembrolizumab with hypofractionated radiotherapy in patients with metastatic solid tumours.

Maity Amit A Mick Rosemarie R Huang Alexander C AC George Sangeeth M SM Farwell Michael D MD Lukens John N JN Berman Abigail T AT Mitchell Tara C TC Bauml Josh J Schuchter Lynn M LM O'Hara Mark M Lin Lilie L LL Demichele Angela A Christodouleas John P JP Haas Naomi B NB Patsch Dana M DM Hahn Stephen M SM Minn Andy J AJ Wherry E John EJ Vonderheide Robert H RH

British journal of cancer 20181015 10

<h4>Background</h4>We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers.<h4>Methods</h4>There were two strata (12 patients each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. Patients had ≥2 lesions; only one was irradiated (8 Gy × 3 for first half; 17 Gy × 1 for second half in each stratum) an ...[more]

PMID: 30318516

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Dataset Information

A phase I trial of pembrolizumab with hypofractionated radiotherapy in patients with metastatic solid tumours.

Background

Methods

Results

Conclusions

Clinical trial registration

Publications

A phase I trial of pembrolizumab with hypofractionated radiotherapy in patients with metastatic solid tumours.

Similar Datasets

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