Table 1 Select clinical trials of immune checkpoint inhibition combined with radiotherapy.
Agent class | Clinical trial ID (reference) | Study name (phase) | Year | Tumor type | Radiotherapy modality | Treatment setting | Number of cases (median age, sex) | Outcomes |
|---|---|---|---|---|---|---|---|---|
Anti-PD-1/PD-L1 | NCT02105636 [129] | CheckMate-141 (III) | 2016 | Head and neck squamous cell carcinoma | Prior radiotherapy (91.4%) | Recurrent disease | 361 (60, 83.1% M) | Increased median OS with nivolumab (7.5 months) vs. standard therapy (5.1 months) |
NCT02125461 [75] | PACIFIC (III) | 2017 | Non–small-cell lung cancer | Definitive radiotherapy concurrent with chemotherapy | Consolidation therapy with placebo in patients with stage III NSCLC | 713 (64, 70.2% M) | Increased 5-year survival with duvalumab after CRT (42.9%) vs. placebo (33.4%) | |
NCT02492568 [130] | PEMBRO-RT (II) | 2019 | Non–Small Cell Lung Cancer | SBRT | Advanced disease | 76 (62, 57.5% M) | Increases in ORR and median PFS were observed with pembrolizumab but did not reach statistical significance | |
NCT03807765 [131] | Nivolumab and Stereotactic Radiosurgery for Patients With Breast Cancer Brain Metastases | 2021 | Breast Cancer Brain Metastases | SRS (post-nivolumab) | Metastatic disease | 12 (58, 0% M) | No dose limiting toxicities were reported. 4/12 patients experienced systemic progression during study | |
NCT02684253 [76] | Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma (II) | 2021 | Head and neck squamous cell carcinoma | SBRT | Metastatic disease | 62 (63, not provided) | No significant difference in ORR, OS, or response duration. Grade 3–5 toxicities were similar. | |
NCT02952586 [132] | JAVELIN Head and Neck 100 (III) | 2021 | Head and neck squamous cell carcinoma | IMRT | Locally advanced disease | 697 (60, 83% M) | No significant difference in median PFS (stopped for futility) | |
NCT03519971 [81] | PACIFIC-2 trial (III) | 2023 | Unresectable, stage III NSCLC | Concurrent chemoradiotherapy | Unresectable disease | 328 (not provided) | No significant difference in PFS with durvalumab vs. CRT alone | |
NCT03040999 [133] | KEYNOTE-412 | 2024 | Head and neck squamous cell carcinoma | Concurrent chemoradiotherapy | Locally advanced disease | 804 (58, 82% M) | No significant difference in event-free survival | |
PD-1 + CTLA4 | NCT02320058 [134] | CheckMate-204 | 2021 | Melanoma brain metastases | SRS | Asymptomatic and symptomatic patients | 94 (59; 68% M) | 3-year response, OS, and median PFS rates were favorable in asymptomatic patients receiving ipilimumab and nivolumab. However, symptomatic patients demonstrated less benefit |
NCT04785287 [135] | Anti-CTLA-4-NF mAb (BMS986218), Nivolumab, and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Malignancies | Ongoing | Solid metastatic cancer | SBRT | Metastatic cancer with ≥ metastatic or primary lesion in bone, adrenal, liver, or lung/chest | 13 (not provided) | Ongoing | |
Anti-CTLA-4 | NCT00861614 [136] | Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043) (III) | 2014 | Prostate cancer | Bone-directed radiotherapy followed by either ipilimumab or placebo | Metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy | 799 (69, 100% M) | No significant difference in OS between ipilimumab and placebo groups, although authors noted that there were signs of drug activity which warrant additional investigation |
NCT02221739 [137] | Radiotherapy induces responses of lung cancer to CTLA-4 blockade (II) | 2018 | NSCLC | External beam with linear accelerator with IGRT or IMRT | Chemo-refractory metastatic NSCLC | 21 (69, 50%); 40/9% with brain metastases | Objective radiographic responses reported in 18% of enrolled patients, with 31% of patients with disease control. | |
NCT02239900 [138] | Phase II Trial of Ipilimumab with Stereotactic Radiation Therapy for Metastatic Disease | 2019 | Metastatic lesions in the liver or lung | Concurrent or sequential stereotactic ablative radiotherapy | Metastatic cancer with at least one metastatic lesion in the liver, lung, or adrenal glands | 106 (60, 47% M) | Median PFS time was 2.9 months and median OS time was not reached. An exploratory analysis found that lesions receiving low-dose radiation were more likely to respond than those which were not irradiated |
