Table 2 Ongoing trials of SBRT in combination with PD-1/PD-L1 inhibitors in NSCLC treatment

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.