Table 2.
Ongoing trials of SBRT in combination with PD-1/PD-L1 inhibitors in NSCLC treatment
| NCT number | Phase | NSCLC stage | SBRT regimen | PD-1/PD-L1 inhibitors | Trial design (Arms) | Primary outcome | Notes |
|---|---|---|---|---|---|---|---|
| NCT03050554 | Phase 1, Phase 2 | Early stage | 12 Gy × 4 fractions or 10 Gy × 5 fractions over 10–12 days every other day |
Avelumab 10 mg/kg q2w for 6 cycles |
SBRT + avelumab | Safety and tolerability of the combination treatment; RFS | To investigate the efficacy of SBRT combined with avelumab in the treatment for early stage NSCLC |
| NCT03924869 | Phase 3 | medically inoperable stage I or IIA | 45–54 Gy/3–5 fractions over approximately 2 weeks every 3 days |
Pembrolizumab 200 mg q3w for up to 17 cycles |
Experimental: SBRT + pembrolizumab Placebo comparator: SBRT + placebo |
EFS (up to approximately 6 years); OS (up to approximately 6 years) | To explore the efficacy and safety of SBRT plus pembrolizumab in the treatment of medically inoperable Stage I or IIA NSCLC. |
| NCT03383302 | Phase 1, Phase 2 | Stage I and II | 18 Gy × 3 fractions or 11 Gy × 5 fractions |
Nivolumab 240 mg q2w for up to 1 year |
Nivolumab + SBRT | Assessment of lung toxicity (pneumonitis)[6 months from final dose of SBRT administered for each patient ] | To assess the lung toxicities from treatment with nivolumab after SBRT for early stage NSCLC |
| NCT03574220 | Phase 1 | Medically inoperable early stage | 50 Gy in 5 fractions over 5–14 days, or 60 Gy in 3 fractions over 8–15 days. |
Pembrolizumab 200 mg q3w for up to 6 months |
Pembrolizumab + SBRT | Percent of patients tolerant to study drug (up to 12 months) | To explore the efficacy of SBRT combined with pembrolizumab in the treatment of medically inoperable early stage NSCLC |
| NCT02599454 | Phase 1 | Stage I | 50Gy in 4 fractions for peripherally located tumors and 50 Gy in 5 fractions for centrally located tumors |
Atezolizumab Courses repeat every 3 weeks |
Atezolizumab + SBRT | Maximum tolerated dose (9 weeks) | To investigate the toxicities and best dose of atezolizumab that can be given together with SBRT in treating patients with stage I NSCLC that cannot be removed by surgery |
| NCT03217071 | Phase 2 | stage I–IIIA | 12 Gy in 1 fraction |
Pembrolizumab 200 mg q3w for 2 cycles |
Pembrolizumab vs. pembrolizumab + SBRT | Change in number of infiltrating CD3+ T cells/μm2 | To determine whether neoadjuvant pembrolizumab +/− SRT is sufficient to produce a two-fold change in the CD3+ T cell population, comparing pre-treatment biopsy tissue to post-treatment resection specimens |
| NCT03436056 | Phase 1 | Stage IV | 30 Gy in 3 fractions, 54 Gy in 3 fractions, the maximum tolerated dose determined before |
Pembrolizumab 200 mg q3w |
Dose escalation cohort 1, SBRT 30 Gy 3 fractions + pembrolizumab Dose escalation cohort 2, SBRT 54 Gy 3 fractions + pembrolizumab Expansion cohort, maximum tolerated dose determined before +p embrolizumab |
Toxicity rate, (12 weeks from the last dose of lung SBRT) establish the recommended dose of SBRT (12 weeks from the last dose of lung SBRT) | To explore the safety of SBRT combined with pembrolizumab and establish the recommended dose for phase 2 trials of lung SBRT that can be safely combined with pembrolizumab. |
| NCT03867175 | Phase 3 | Stage IV | 3–10 treatments of SBRT |
Pembrolizumab 200 mg q3-4w for up to 1 year |
Experimental arm, SBRT + pembrolizumab Control arm, Pembrolizumab alone |
PFS (up to 5 years) | To explore how well SBRT combined with immunotherapy works compared with immunotherapy alone after first-line systemic therapy in patients with stage IV NSCLC |
| NCT02904954 | Phase 2 | Stage I, II, and IIIA | SBRT delivered in 3 daily fractions | Durvalumab |
Experimental arm, Durvalumab + SBRT Control arm, Durvalumab alone |
Disease-free survival (up to 26 months) | To find out the effectiveness of durvalumab with or without SBRT as treatment for stage I, II, and IIIA NSCLC prior to surgery and 1 year following surgery |
| NCT03589547 | Phase 2 | Stage III | 20 Gy in 2 fractions |
Durvalumab 10 mg/kg q2w for up to 1 year |
Durvalumab + SBRT |
Number of patients experiencing grade 2 or higher toxicities during combination therapy (the first 3 months of durvalumab) Average PFS (for about 5 years) |
To investigate the safety and efficacy of the combination of durvalumab and SBRT. |
| NCT03148327 | Phase 1, Phase 2 | non-metastatic, early stage | 54 Gy in 3 fractions or 50 Gy in 4 fractions or 65 Gy in 10 fractions |
Durvalumab 1500 mg q4w for up to 4 cycles |
SBRT + durvalumab SBRT alone |
treatment-related adverse events as assessed by CTCAE v4.0(4 months), mPFS (2 years) | To explore the safety and efficacy of the combination of durvalumab and SBRT vs. SBRT alone |
| NCT03110978 | Phase 2 | Stage I, selected stage IIa or isolated | SBRT |
Nivolumab For up to 12 weeks |
SBRT alone SBRT + nivolumab |
Event-free survival (EFS) [2 years] | To investigate the efficacy of SBRT combined with nivolumab in patients with stage I–IIA NSCLC |
| NCT03446547 | Phase 2 | Stage I | SBRT 3–4 fractions |
Durvalumab 1500 mg q4w for up to 1 year |
Arm A, SBRT Arm B, SBRT + durvalumab |
Time to progression (TTP) | To explore the efficacy of SBRT combined with durvalumab in patients with stage I NSCLC |
| NCT03833154 | Phase 3 | Early stage | SBRT |
Durvalumab 1500 mg q4w for up to 2 year |
Experimental arm, Durvalumab + SBRT Control arm, Placebo + SBRT |
PFS (up to 5 years) | To assess the efficacy and safety of durvalumab versus placebo following SBRT in patients with unresected Stage I/II lymph node-negative NSCLC. |
| NCT02407171 | Phase 1, Phase 2 | Stage IV | 30 Gy in 5 fractions, 30 Gy in 3 fractions, 10 Gy in 1 fraction |
Pembrolizumab 200 mg q2w |
SBRT + pembrolizumab |
ORR (up to 12 months) Dose-limiting toxicity (up to 12 months) |
To explore the efficacy and safety of SBRT combined with pembrolizumab in metastatic NSCLC. |
| NCT02444741 | Phase 1, Phase 2 | Stage IV | 50 Gy in 4 fractions or 45 Gy in 15 fractions |
Pembrolizumab 200 mg q2w |
SBRT + pembrolizumab | ORR; incidence of toxicity; maximum tolerated dose of pembrolizumab and SBRT | To explore the efficacy and safety of SBRT combined with pembrolizumab in stage IV NSCLC. The research also aims to compare different types of radiotherapy. |
| NCT02608385 | Phase 1 | Stage IV | 3 or 5 doses of SBRT to the chosen metastases |
Pembrolizumab 200 mg q3w |
SBRT + pembrolizumab | Recommended SBRT dose in combination with Pembrolizumab. | To evaluate the safety of SBRT combined with pembrolizumab and determine the safe doses of radiation when used together with pembrolizumab. |
| NCT02658097 | Phase 2 | Stage IV | 8 Gy in 1 fraction |
Pembrolizumab 200 mg q3w |
SBRT + Pembrolizumab | ORR | To explore the efficacy of SBRT combined with pembrolizumab with some focus on the tumor responses outside the radiation field. |
| NCT02492568 | Phase 2 | Stage IV | 24 Gy in 3 fractions |
Pembrolizumab 200 mg q3w for up to 2 years |
SBRT + pembrolizumab vs. pembrolizumab alone | ORR | To evaluate the increase in ORR in the pembrolizumab alone arm compared to the pembrolizumab after SBRT arm at 12 weeks |
| NCT03812549 | Phase 1 | Stage IV | 30 Gy in 3 fractions |
Sintilimab 200 mg q3w for up to 2 years |
SBRT + low dose radiotherapy (LDRT) dose from 2 to 10 Gy + sintilimab vs. SBRT + LDRT dose at MTD determined + sintilimab | Number of participants with adverse events and dose limiting toxicities | To investigate the safety and tolerability of sintilimab in combination with concurrent SBRT and low dose radiotherapy in patients with stage IV NSCLC |
| NCT03275597 | Phase 1 | Stage IV | 30 and 50 Gy in five fractions over 2 weeks |
Durvalumab 1500 mg q4w Tremelimumab 75 mg q4w |
SBR + durvalumab + tremelimumab | Safety and tolerability | To evaluate safety and tolerability of dual checkpoint inhibition of durvalumab and tremelimumab with SBRT in the treatment of oligometastatic NSCLC and to examine the sequential delivery of SBRT to all disease sites followed by combination of durvalumab and tremelimumab. |
| NCT04238169 | Phase 2 | Stage IV | 30–50 Gy in 5 fractions |
Toripalimab 240 mg q3w for 9 cycles |
SBRT + toripalimab vs. SBRT + Bevacizumab + toripalimab |
ORR | To investigate the effect of SBRT and immunotherapy combined with bevacizumab or not in stage IV NSCLC with previously failed after chemotherapy. |
| NCT04255836 | Phase 2 | oligo-metastatic | 50–60 Gy/≤ 10 fractions | Durvalumab 1500 mg q3w for 4 cycles and 1500 mg q4w for 2 years | Durvalumab + chemotherapy + SBRT | PFS | To assess the efficacy and safety of durvalumab combined with chemotherapy and SBRT in patients with oligo-metastatic NSCLC |
| NCT03955198 | Phase 2 | Advanced NSCLC with 1 to 4 brain metastases | SBRT | Durvalumab | SBRT vs. SBRT + durvalumab | Time to intra-cranial progression | To evaluate whether the combination of SBRT with durvalumab in patients with brain metastases from NSCLC improves brain tumor control compared to SBRT alone. |
NSCLC non-small cell lung cancer, SBRT stereotactic body radiotherapy, SABR stereotactic ablative radiotherapy, RFS relapse free survival, EFS event-free survival, OS overall survival, PFS progression-free survival, TTP time to progression, ORR overall response rate