Table 1.
Summary of the most important preclinical and clinical studies investigating radioimmunotherapy in patients with NSCLC
| Completed trials | ||||
|---|---|---|---|---|
| Phase | ClinicalTrials.gov identifier | Setting | Treatment | Results |
| Ib | NCT00879866 | Metastatic NSCLC with disease control after first-line platinum-based chemotherapy | NHS-IL2, in combination with palliative RT to the primary tumor or metastasis (20 Gy in 5 daily fractions) |
Median PFS 8.9 months Median OS 8.6 months |
| I | NCT00455572 | Unresectable stage III NSCLC (1 of 4 study cohorts) | 2 cycles of CT followed by sequential RT and then MAGE-A3 IO | Well-tolerated and induces MAGE-A3-specific immune responses |
| II | NCT02221739 | Chemo-refractory advanced NSCLC | Ipilimumab within 24 h of starting palliative RT to at least one metastatic lesion (30 Gy in 5 fractions) | 2 CR, 3 PR/SD and 7 PD |
| II | NCT02525757 | Stage III NSCLC | Concurrent atezolizumab and CTRT followed by atezolizumab consolidation and maintenance |
Median PFS 20.1 months 12-month OS rate 60/77% (preliminary data) |
| II | NCT02343952 | Unresectable stage III NSCLC | Consolidation pembrolizumab following concurrent CTRT | Median TMDD not reached, (estimates of 1-year and 2-year OS: 80.5 and 68.7%, respectively) |
| III | NCT00676507 | Stage IIIB/IV NSCLC who had not progressed on either prior CT or CTRT | Maintenance tecemotide (L-BLP25) versus placebo | No OS benefit |
| III | NCT00409188 | Stage IIIA/IIIB NSCLC | Maintenance tecemotide (L-BLP25) versus placebo following concurrent or sequential CTRT | No OS benefit |
| III | NCT02125461 | Stage III NSCLC who did not have PD after 2 or more cycles of CTRT | Maintenance durvalumab versus placebo |
Median PFS 17.2 months (HR 0.51; 95% CI, 0.41–0.63) 24-month OS rate 66.3% (HR 0.68; 99.73% CI, 0.47–0.997; P = 0.0025) |
| Trials in progress | ||||
| I | NCT03224871 | Stage IV NSCLC with PD following checkpoint blockade treatment | Checkpoint blockade continued (nivolumab or pembrolizumab), intralesional IL-2 (× 4) combined with RT | Ongoing |
| I | NCT03245177 | Unresectable stage III NSCLC unsuitable for concurrent chemoradiation for radical RT (± sequential chemotherapy) | Pembrolizumab started 14 days prior to RT and continued to 12 months as maintenance | Ongoing |
| I | NCT03368222 | Stage IIIB/IV NSCLC with PD following 1st-line chemotherapy | Pembrolizumab commencing 14 days before RT and continued for up to 2 years | Ongoing |
| I | NCT02987998 | Stage IIIA NSCLC treated with neoadjuvant chemoradiation prior to surgery | Pembrolizumab added to concurrent CTRT and continued as maintenance | Ongoing |
| I/II | NCT03168464 | Metastatic NSCLC with PD and at least 2 metastases | Ipilimumab concurrent with RT day 1; ipilimumab plus nivolumab from day 22 until PD | Ongoing |
| I/II | NCT02696993 | Stage IV NSCLC with brain metastases | Nivolumab or nivolumab/ipilimumab in combination with WBRT | Ongoing |
| I/II | NCT03110978 | Early-stage NSCLC | Nivolumab commencing within 24 h of final fraction RT (SABR) and continued for 12 months | Ongoing |
| II | NCT02434081 | Unresectable stage III NSCLC | Four doses of nivolumab concurrent with CTRT followed by up to 12 months maintenance nivolumab | Ongoing |
| II | NCT03379441 | Unresectable stage III NSCLC treated with sequential/concurrent chemoradiation | Sequential maintenance pembrolizumab | Ongoing |
| II | NCT02658097 | Previously treated stage IV NSCLC | Pembrolizumab commencing day of RT; randomized between RT and no RT | Ongoing |
| II | NCT02492568 | Stage IV NSCLC following 1st-line chemotherapy | Randomized between pembrolizumab alone or pembrolizumab commencing within 1–2 weeks of RT (SABR) | Ongoing |
| II | NCT03044626 | Stage IV non-squamous NSCLC requiring RT to metastasis in 2nd/3rd-line treatment | Nivolumab commencing 72 h before RT | Ongoing |
| II | NCT03035890 | Stage IV NSCLC with PD following chemotherapy | IO concurrent with RT (nivolumab or pembrolizumab or atezolizumab allowed) | Ongoing |
| II | NCT03217071 | Stages I–IIIA NSCLC planned for surgical resection | Randomized to 2 cycles neoadjuvant pembrolizumab alone or pembrolizumab with RT following 2nd IO infusion followed by surgery | Ongoing |
| III | NCT03391869 | Stage IV NSCLC | Induction ipilimumab/nivolumab followed by randomization to maintenance IO or local therapy (i.e. RT or surgery) | Ongoing |
| III | NCT02768558 | Unresectable stage III NSCLC treated with concurrent CTRT | Randomized to nivolumab or placebo twice weekly for 12 months following CTRT | Ongoing |
NSCLC non-small cell lung cancer, NHS-IL2 necrotic DNA-specific antibody conjugated with a modified human IL-2, RT radiotherapy, PFS progression-free survival, OS overall survival, CR complete response, PR partial response, SD stable disease, PD progressive disease, CT chemotherapy, IO immunotherapy, SABR stereotactic ablative radiotherapy